Role of bridging RT in relapsed/refractory diffuse large B-cell lymphoma undergoing CAR-T therapy: a multicenter study

Role of bridging RT in relapsed/refractory diffuse large B-cell lymphoma undergoing CAR-T therapy: a multicenter study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Role of bridging RT in relapsed/refractory diffuse large B-cell lymphoma undergoing CAR-T therapy: a multicenter study Daniele Mannina, Stefania Bramanti, Annalisa Chiappella, Beatrice Casadei, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3573162/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Oct, 2024 Read the published version in Bone Marrow Transplantation → Version 1 posted 10 You are reading this latest preprint version Abstract The optimization of bridging regimen before chimeric antigen receptor (CAR)-T cell therapy in diffuse large B-cell lymphoma (DLBCL) may impact CAR-T efficacy and outcome. This retrospective study evaluates CAR-T outcome after bridging with radiotherapy (RT) and other bridging strategies. Among 148 patients with relapsed/refractory DLBCL who underwent leukapheresis for CAR-T manufacturing, 31 received RT-bridging, 84 chemotherapy (CT), 33 no-bridging or steroid-only. CAR-T cell were infused in 96.8% of RT-group. 89.2% of CT-group and 78.8% of no-bridge group (p = 0.079). Response to bridging was generally poor, but patients receiving RT had a significant reduction in LDH levels between pre- and post-bridging (p = 0.05). The one-year PFS was 51.2% in the RT group, 28.2% in the CT group, and 47.6% in the no-bridge group (p = 0.044); 1-year OS was 86.7% in the RT group, 52.7% in the CT group and 69% in the no-bridge group (p = 0.025). We observed a higher incidence of ICANS in patients who received CT than in others (20.0% CT group, 3.3% RT group, 7.7% no-bridge group; p = 0.05). In conclusion, RT-bridging is associated with lower drop-out rate and CAR-T toxicity, and it might be preferred to other bridging strategies for patients with localized disease or for those with one prevalent symptomatic site. Health sciences/Diseases/Cancer/Cancer therapy/Cancer immunotherapy Health sciences/Diseases/Cancer/Haematological cancer/Lymphoma/Non-hodgkin lymphoma/B-cell lymphoma Figures Figure 1 Figure 2 KEY POINTS In relapsed/refractory diffuse large B-cell lymphoma, RT-based bridge can be associated with reduced drop-out rate and CAR-T toxicity. INTRODUCTION Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy is an effective treatment option for relapsed/refractory diffuse large B-cell lymphoma (DLBCL). 1 CAR-T manufacturing and delivery usually requires 3–4 weeks. Because of the disease’s aggressive nature, in the period between lymphocyte collection and lymphodepleting chemotherapy (CT), DLBCL can be highly symptomatic or life-threatening, limiting the possibility of administering CAR-T infusion. 2 Therefore, a bridging regimen is required for most patients during the manufacturing of CAR-T to control disease progression and potentially reduce disease burden without adding toxicity, with the aim of bringing all the candidates to the CAR-T infusion. The bridging strategy is not standardized and ranges from steroids only to CT, targeted therapy, immunotherapy, or radiotherapy (RT). 3 – 5 The efficacy of the bridging regimen can significantly impact the efficacy and toxicity of CAR-T treatment. 6 , 7 Real-life registry data show that patients who do not need bridging therapy have a better outcome. 8 Furthermore, a large disease volume is negatively associated with post-CAR-T progression-free survival (PFS) and is also a risk factor for cytokine-release syndrome (CRS). 9 Therefore, strategy optimization for patients needing bridging therapy may be important to improve CAR-T efficacy and toxicity. 8 CT-resistant, relapsed/refractory aggressive B-cell lymphomas may be sensitive to RT. 10 – 12 Preclinical data also suggest that RT can potentially enhance the efficacy of immunotherapy via antigen exposure (abscopal effect). 13 , 14 Moreover, using RT instead of drugs can minimize the impact on blood counts, organ function, and performance status of bridging therapy. However, comparative clinical data on RT versus CT as a bridging regimen to CAR-T are still scant. Based on these premises, we retrospectively evaluated the potential impact of different bridging strategies in terms of efficacy and toxicity. PATIENTS AND METHODS Setting and design We retrospectively collected consecutive patient candidates for CAR-T treatment for relapsed/refractory DLBCL from September 2019 to April 2022 in a real-life setting. The enrolment was multicentric, involving three Italian referral centers: IRCCS Humanitas Research Hospital (Rozzano, Italy), IRCCS Fondazione Istituto Nazionale dei Tumori (Milan, Italy), and Istituto Seràgnoli Policlinico Sant’Orsola, Bologna, Italy. The protocol was written, and the study was conducted according to the International Guideline for Good Clinical Practice. The protocol and its annexes were approved by the competent Independent Ethics Committees (“IEC”) of the enrolling Centers (ONC/OSS-18/2021, ICH-3068). Patients All patients diagnosed with DLBCL relapsed or refractory to at least two lines of therapy who underwent leukapheresis for CAR-T manufacturing (tisagenlecleucel (tisa-cel), or axicabtagene ciloleucel (axi-cel)) were included. Patients receiving CAR-T treatment within an investigational study were excluded. Treatment Bridging therapy is defined as any treatment (CT, RT, steroids, other) administered from the date after the apheresis to the start of lymphodepleting therapy. All patients received a lymphodepleting regimen according to the standard guidelines for any CAR-T product. The decision to treat a patient with a bridging regimen was made in case of symptomatic or rapidly progressive disease. Among the patients needing a bridge, the criteria for choosing RT alone over a CT-containing regimen were the presence of localized disease or disseminated disease with a main symptomatic site. The cohort was divided into three groups: patients who did not receive any bridge (no-bridge group), patients who received RT-based bridge alone (RT group), and patients who received any other CT-based bridge (CT group). According to Lugano criteria, disease evaluation with CT/PET scan was performed after bridging therapy and CAR-T therapy at day + 30 and + 90 after infusion. 15 Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were diagnosed and classified according to autologous stem cell transplantation (ASTCT) criteria 16 and were managed according to local guidelines. Objective and endpoints The study’s objective was to evaluate the outcome of all patients who were candidates for CAR-T treatment across the three groups. Firstly, we analyzed the direct response to bridging therapy in terms of the treatment’s ability to ensure disease control during the manufacturing period. Subsequently, we comparatively analyzed PFS (defined as the time from CAR-T infusion to disease progression, death, or loss to follow-up, whatever occurred first) and overall survival (OS; defined as the time from CAR-T infusion to death or loss to follow-up, whatever occurred first) after CAR-T infusion in the different groups. Other endpoints were the incidence of CRS, ICANS, and infections after CAR-T infusion. Statistical analysis Data were summarized as frequencies and proportions or medians, and range and differences were estimated by the Chi-square test (the Fisher exact test when appropriate) for categorical variables. The Logistic regression methods were used to estimate the odds ratio and their corresponding 95% confidence intervals (CI) in univariate and multivariate analysis. Survival curves were estimated by the Kaplan-Meier method, and the log-rank test assessed the differences between groups. The multivariate Cox model was used to estimate the hazard ratio (HR) and their corresponding 95% CI. Statistical significance was set at 0.05 level. All analyses were performed using SAS version 9.4. RESULTS Study population We enrolled 148 DLBCL patients (136 DLBCL, 12 transformed from low-grade B-cell lymphoma). Of them, 92 (62.2%) were males; the median age was 60 years (range 21–73) (Table 1 ). Most patients (60.1%) received two previous lines before CAR-T indication, 23.6% three previous lines, and 14.9% four or more lines. Only 14.2% had relapsed after responding to previous treatment, whereas most patients (85.8%) had a primary refractory disease. About one out of four patients (24.2%) had received ASCT. Double/triple-hit lymphoma was reported in 16.2% of cases. Table 1 Patient characteristics at baseline. CT group (n = 84) RT group (n = 31) No-bridge group (n = 33) Total (n = 148) CAR-T Infused 75 (89.2%) 30 (96.8%) 26 (78.8%) 131 (88.5%) Dead before infusion 8 (9.5%) 1 (3.2%) 5 (15.1%) 14 (9.5%) Alive but not infused 1 (1.3%) - 2 (6.1%) 3 (2%) Age Mean (range) 58 (21–73) 57 (21–70) 60 (29–71) 58 (21–73) p = 0.83 Sex Male 49 (58.3%) 21 (67.7%) 22 (66.7%) 92 (62.2%) p = 0.54 Female 35 (41.7%) 10 (32.3%) 11 (33.3%) 56 (37.8%) Diagnosis DLBCL 77 (91.7%) 29 (93.5%) 30 (90.9%) 136 (91.9%) p = 1 .00 t-DLBCL 7 (8.3%) 2 (6.5%) 3 (9.1%) 12 (8.1%) Previous lines 2 50 (59.5%) 20 (64.5%) 19 (57.6%) 89 (60.1%) p = 0.44 3 18 (21.4%) 8 (25.8%) 9 (27.3%) 35 (23.6%) 4 9 (10.7%) 1 (3.2%) 0 (-) 10 (6.7%) 5 or more 6 (7.1%) 2 (6.5%) 4 (12.1%) 12 (8.1%) Missing 1 (1.2%) 1 (3.0%) 2 (1.4%) Double-hit phenotype Yes 12 (14.3%) 10 (32.3%) 2 (6.1%) 24 (16.2%) p = 0.02 No 72 (85.7%) 21 (67.7%) 31 (93.9%) 124 (83.8%) Double-expressor phenotype Yes 22 (26.2%) 10 (32.2%) 9 (27.2%) 41 (27.7%) p = 0.84 No 41 (48.8%) 14 (45.2%) 16 (8.6%) 71 (48%) Not available 21 (25%) 7 (22.6%) 8 (24.2%) 36 (24.3%) Stage at diagnosis I 3 (4.8%) 1 (3.2%) 0 (-) 4 (2.7%) p = 0.55 1 II 14 (16.7%) 7 (22.6%) 3 (9.1%) 24 (16.3%) III 11 (13.1%) 4 (12.9%) 8 (24.2%) 23 (15.4%) IV 55 (65.5%) 19 (61.3%) 22 (66.7%) 96 (64.9%) Missing 1 (1.2%) 1 (0.7) Relapsed/refractory to last treatment Relapsed 11 (13.1%) 4 (12.9%) 6 (18.2%) 21 (14.2%) p = 0 .76 Refractory 73 (86.9%) 27 (87.1%) 27 (81.8%) 127 (85.8%) Prior ASCT Yes 19 (22.6%) 12 (38.7%) 5 (18.2%) 36 (24.3%) p = 0 .08 No 65 (77.4%) 19 (61.3%) 28 (81.8%) 112 (75.7%) CAR-T product Tisa-cel 61 (72.6%) 15 (48.4%) 17 (51.5%) 93 (62.8%) p = 0.02 Axi-cel 23 (27.4%) 16 (51.6%) 16 (48.5%) 55 (37.2%) Stage at leukapheresis I 2 (2.4%) 2 (6.5%) 0 (-) 4 (2.7%) p = 0.77 1 II 14 (16.7%) 5 (16.1%) 6 (18.2%) 25 (16.9%) III 13 (15.4%) 2 (6.5%) 6 (18.2%) 21 (14.2%) IV 55 (65.5%) 22 (70.9%) 21 (63.6%) 98 (66.2%) Apheresis-to-infusion time Median (range) 47 (21–96) 49 (21–96) 47 (30–80) 41 (31–90) ECOG performance status 0 54 (64.3%) 25 (80.6%) 25 (75.7%) 104 (70.3%) p = 0.17 1 30 (35.7%) 6 (19.4%) 8 (24.3%) 44 (29.7%) LDH at leukapheresis IU/L Mean 425 325 330 383 p = 0.09 3 LDH at lymphodepletion IU/L Mean 405 254 329 356 p = 0.21 3 p value 2 p = 0.42 p = 0.05 p = 0.84 p = 0.22 Ferritin at leukapheresis mg/dl Mean 588 492 423 534 p = 0.34 3 Ferritin at lymphodepletion mg/dl Mean 734 713 750 733 p = 0.97 3 p value 2 p = 0.12 p = 0.80 p = 0.01 p = 0.49 CRP at leukapheresis mg/dl Mean 9.8 10.1 2.1 8.2 p = 0.09 3 CRP at lymphodepletion mg/dl Mean 11 8.8 6.5 9.6 p = 0.21 3 p value 2 p = 0.69 p = 0.71 p = 0.03 p = 0.49 1 p value for III-IV vs I-II 2 paired t-test (pre-bridge vs post-bridge) 3 t-test between bridge groups Thirty-one patients were treated with RT alone, 33 did not receive any bridge (or received steroid-only), and 84 received various drug combinations (Table 2 ). No differences across the study groups were disclosed in terms of baseline characteristics. Table 2 Bridging strategies Group Type of bridge N of patients CT bridge Chemo-immunotherapy 71 Chemo-immunotherapy + local RT 8 Lenalidomide 2 Anti-CD3-CD20 bispecific andibody 2 Anti-CD19 immunoconjugate 1 RT bridge Single-site radiotherapy 31 Mean dose: 28 Gy (Range 17,5–36 Gy) Mean n. of fractions: 11 (range 5–20) Administration of CAR-T infusion Of the 148 enrolled patients, 17 (11.5%) could not receive the infusion, and 131 (88.5%) underwent CAR-T therapy: 82 patients received tisa-cel and 49 axi-cel. CAR-T products were axi-cel for 37.2% of patients and tisa-cel for 62.8%. The reasons for not receiving CAR-T were disease progression in 12 of 17 cases (70.5%), COVID-19 infection in three of 17 cases (17.5%), psychiatric disturbance in one of 17 cases (6%); one patient was not infused because of complete remission (CR) after bridging therapy. The probability of receiving CAR-T infusion was 96.8% in the RT group (30/31), 89.2% in the CT group (75/84), and 78.8% in the no-bridge group (26/33), respectively (p = 0.079). Mortality among patients who did not receive CAR-T infusion was 82% (14/17), and the cause was disease progression in 12/14 cases, Covid19 in 2/14 cases. Before CAR-T infusion, most patients (90%) in the no-bridge group (including steroid-only) showed disease progression. A disease evaluation after bridging therapy was available immediately before CAR-T infusion for 126 of 148 patients. Disease progression had a similar rate across the study groups (76.7% in the RT group, 73.7% in the CT group, and 90% in the no-bridge group; p = 0.332). The analysis of biomarkers, such as LDH, ferritin, and C-reactive protein (CRP), showed no statistically significant difference across the bridge groups. We observed a significant decrease in LDH between leukapheresis and post-bridging time within the RT group and a significant increase in ferritin and CRP levels in the group not receiving any bridge (Table 1 ). CAR-T efficacy At day 30 after CAR-T infusion, CR was achieved in 43.5% of patients: 50% of patients in the RT group, 38.7% of those in the CT group, and 50% of those in the no-bridge group (p = 0.469) [Table 3 ]. At day 90 after CAR-T infusion, CR was reached in 53.2% of evaluable patients (n = 109): 59.3% of patients in the RT group, 45.8% of those in the CT group, and 65.2% of those in the no-bridge group (p = 0.218 for CR vs no CR). Table 3 Response at day 30 after CAR-T by group in 131 evaluable patients Response CT group n = 75 (col %) RT group n = 30 (col %) No-bridge group n = 26 (col %) All infused n = 131 (col %) CR 29 (38.7%) 15 (50%) 13 (50%) 57 (43.5%) PR 15 (20%) 7 (23.3%) 4 (15.4%) 26 (19.8%) SD 5 (6.7%) 1 (3.4%) 2 (7.7%) 8 (6.1%) PD 25 (33.3%) 7 (23.3%) 7 (26.9%) 39 (29.8%) NA 1 (1.3%) - - 1 (0.8%) P value for CR vs no CR: 0.469 With a median follow-up of 17 months from leukapheresis, the 1-year PFS and OS of the entire cohort were 37.6% and 63.6%, respectively. One-year PFS was 51.2% in the RT group, 28.2% in the CT group, and 47.6% in the no-bridge group, while 1-year OS was 86.7% in the RT group, 52.7% in the CT group, and 69% in the no-bridge group, respectively (Figs. 1 – 2 ). Multivariate analysis for factors associated with PFS and OS showed that the type of bridge (CT-based bridge vs RT-based bridge; p = 0.025, p = 0.044, respectively) and stage at leukapheresis (stage IV vs I–III; p = 0.003, p = 0.014, respectively) were associated with poorer outcome (Table 4 ). Performance status was significantly associated only with OS (ECOG 1 vs 0; p = 0.053) (Table 4 ). It should be considered that ECOG 2 before the CAR-T program, is an exclusion criterion of the Ministry of Health in Italy. Table 4 Multivariate models for progression-free survival (PFS) and overall survival (OS). Parameter P value Hazard ratio Hazard Ratio (95% Confidence Limits) Overall Survival No-bridge vs RT-based bridge 0.391 1.46 0.62 3.45 CT-based bridge vs RT-based bridge 0.044 2.07 1.02 4.21 Stage at lymphodepletion IV vs I-III 0.014 2.19 1.17 4.09 Performance status 1 vs 0 0.053 1.69 0.99 2.87 Progression-free Survival NO-bridge vs RT-based bridge 0.521 1.25 0.63 2.49 CT-based bridge vs RT-based bridge 0.025 1.90 1.09 3.32 Stage at lymphodepletion IV vs I-III 0.003 2.08 1.29 3.35 Toxicity Table 5 shows the rate of infections, CRS, and ICANS after CAR-T. CRS occurred in 80.9% of the entire cohort (4.6%; grade 3–4). CRS incidence was not different between the groups (p = 0.92). ICANS occurred in 13.7% of patients. We observed a statistically significantly higher ICANS incidence in patients who received CT-based bridge than in others (20.0% in the CT group, 3.3% in the RT group, and 7.7% in the no-bridge group). In a multivariate model comparing RT with CT groups, axi-cel use (OR = 42.4; 95% CI: 4.0–447; p = 0.004), baseline basal ECOG PS 1 (OR = 33.3; 95% CI: 0.004–0.3; p = 0.004), and CT-based bridge use (OR = 25.1; 95% CI: 1.8–347.6; p = 0.016) were confirmed as independent negative predictive factors for ICANS. We observed no association between the probability of ICANS and the disease stage at the time of leukapheresis. Table 5 Toxicity across the groups with different bridging therapy. CT group n = 75 N (%) RT group n = 30 N (%) No-bridge group n = 26 N (%) All n = 131 N (%) P value Infections 15 (20%) 7 (23.3%) 2 (7.69%) 24 (18.3%) p = 0.273 CRS 60 (80%) 25 (83.33%) 21 (80.77%) 106 (80.9%) p = 0.926 CRS G 3–4 4 (5.33%) 1 (3.33%) 1 (3.85%) 6 (4.6%) p = 1.00 ICANS 15 (20%) 1 (3.33%) 2 (7.69%) 18 (13.7%) p = 0.056 ICANS G3-4 4 (5.33%) 0 (-) 1 (3.85%) 5 (3.8%) p = 0.823 NRM 4 (5.3%) 1 (3.3%) 1 (3.8%) 6 (1.5%) p = 0.848 CRS = cytokine release syndrome; ICANS = immune effector cell associated neurotoxicity syndrome; NRM = non-relapse mortality events. In the entire cohort, 18.3% of patients had at least one infectious complication; no difference in the incidence of infections was disclosed. Six cases of non-relapse mortality were reported: one in the RT group (COVID-19), one in the no-bridge group (second tumor), and four in the CT group (one COVID-19, one septic shock, two severe neurotoxicity). DISCUSSION In the present study, we compared different bridging strategies on a large cohort of relapsed/refractory DLBCL adult patients who were candidates to receive tisa-cel or axi-cel in a real-life setting. The retrospective nature of the study and the selection bias of bridging strategy can affect the interpretation of our data, given that the bridging regimen has been selected for each patient according to disease characteristics and performance status. Nevertheless, homogeneous criteria for choosing RT bridging were adopted for the whole cohort, consisting in the presence of a prevalent bulky or symptomatic disease, independently from disease stage. In fact, no significant difference in baseline stage and LDH level was observed between the three groups, as shown in Table 1 . This finding suggests that the outcome may have not been directly determined by differences in disease distribution and burden. The first relevant finding of our study was the very low drop-out rate (3.2%) among patients treated with RT as a bridge, compared with those receiving a CT-based regimen (10.2%), but also compared with those receiving no bridging therapy (21.2%). Furthermore, our data showed a better outcome for patients not receiving bridging therapy in terms of OS and PFS. On the other hand, among the patients who needed a bridge, the outcome in terms of PFS and OS was more favorable for the RT group than the other regimens. Bridging success has been reported in previous real-world reports of DLBCL as strongly related to CAR-T outcome. In contrast, the advantage of RT seems unrelated to the direct response to the bridge. 17 Indeed, we observed no difference in bridging failure between the groups. Our data are in line with a retrospective study previously published on axi-cel by Pinnix et al, which showed a better outcome for patients not needing a bridge or those undergoing RT-based bridge than those receiving CT-based bridge. 18 The study’s authors speculatively attributed the poorer outcome to a higher disease burden in patients needing bridging therapy for disease control. Furthermore, the study of Pinnix et al. included only patients treated with axi-cel, known to be more frequently associated with ICANS (up to 64% of treated patients), 19 and the authors did not report any difference in terms of CAR-T toxicity between the different bridging groups. 18 Differently, we reported a significantly lower rate of ICANS among patients in the RT group than in the CT group (1/31 vs 15/75), although the proportion of patients treated with axi-cel was higher in the RT group than in the CT group (16/31 vs 23/75). At multivariate analysis, RT-based bridge significantly reduced the risk of ICANS independently from the type of CAR-T and the Ann Arbor disease stage at the time of lymphodepletion. Considering one of the most well-grounded pathogenic mechanisms of ICANS onset, 20 it could be speculated that exposure to additional (poly-)CT cycles only a few weeks before CAR-T infusion may lead to a higher risk of neuroinflammation by increasing blood–brain barrier (BBB) permeability 21 , 22 and facilitating the diffusion of proinflammatory cytokines in the brain; conversely, patients receiving RT regimen might be protected by ICANS. This study was not planned to verify this hypothesis; the prospective collection of biological data on BBB damage biomarkers before and after CAR-T infusion in the different bridging groups should be considered as a future project. We also found that only in the RT group could the LDH level be reduced by bridging, whereas we observed no improvement in inflammatory biomarkers in the other bridging group. Biomarkers, such as LDH, are related to both disease burden and inflammatory status; current evidence strongly suggests that inflammatory biomarkers are associated with CAR-T efficacy and toxicity. 23 , 25 Consistent with a previous report, 26 we hypothesize that RT has a lower impact on inflammation and endothelial damage than other bridging strategies and that this mechanism may explain the apparent lower toxicity of CAR-T after RT. The type of bridging therapy is only one of the multiple patients- and disease-related factors that can influence the final outcome of CAR-T, in addition to age, comorbidities, general conditions, disease volume, and systemic inflammatory status. 27 – 29 Because of limitations arising from the retrospective nature of this study and the bias given by the non-randomized choice of bridging regimen, our findings cannot be conclusive in guiding the selection of the best bridge for each patient. Nonetheless, in our study, the type of bridging therapy was significantly associated with the drop-out rate and CAR-T toxicity. RT can be seen as an effective strategy to maximize the probability of receiving and then tolerating CAR-T infusion. Declarations Acknowledgments Editorial assistance was provided by Luca Giacomelli, PhD, Valentina Attanasio and Massimiliano Pianta; this assistance was supported by internal funds. Authorship contributions SB, DM and AS designed the study. 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Soussain C, Ricard D, Fike JR, Mazeron JJ, Psimaras D, Delattre JY. CNS complications of radiotherapy and chemotherapy. Lancet. 2009;374(9701):1639–1651. Vercellino L, Di Blasi R, Kanoun S, et al. Predictive factors of early progression after CAR T-cell therapy in relapsed/refractory diffuse large B-cell lymphoma. Blood Adv. 2020;4(22):5607–5615. Westin JR, Kersten MJ, Salles G, et al. Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. Am J Hematol. 2021;96(10):1295–1312. Bachanova V, Westin J, Tam C, et al. Correlative analyses of cytokine release syndrome and neurological events in tisagenlecleucel-treated relapsed/refractory diffuse large B‐cell lymphoma patients. Hematol Oncol. 2019;37(S2):308‐310. Hubbeling H, Silverman EA, Michaud L, et al. Bridging Radiation Rapidly and Effectively Cytoreduces High-Risk Relapsed/Refractory Aggressive B Cell Lymphomas Prior to Chimeric Antigen Receptor T Cell Therapy. Transplant Cell Ther . 2023;29(4):259.e1-259.e10. Bethge WA, Martus P, Schmitt M, et al. GLA/DRST real-world outcome analysis of CAR T-cell therapies for large B-cell lymphoma in Germany. Blood. 2022;140(4):349–358. Nastoupil LJ, Jain MD, Feng L, et al. Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium. J Clin Oncol. 2020;38(27):3119–3128. Ghafouri S, Fenerty K, Schiller G, et al. Real-World Experience of Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed or Refractory Aggressive B-cell Lymphomas: A Single-Institution Experience. Clin Lymphoma Myeloma Leuk. 2021;21(12):861–872. Additional Declarations The authors have declared there is NO conflict of interest to disclose. Cite Share Download PDF Status: Published Journal Publication published 09 Oct, 2024 Read the published version in Bone Marrow Transplantation → Version 1 posted Editorial decision: revise 15 Dec, 2023 Review # 1 received at journal 08 Dec, 2023 Review # 2 received at journal 04 Dec, 2023 Reviewer # 2 agreed at journal 22 Nov, 2023 Reviewer # 1 agreed at journal 18 Nov, 2023 Reviewers invited by journal 17 Nov, 2023 Submission checks completed at journal 09 Nov, 2023 First submitted to journal 08 Nov, 2023 Unknown event 08 Nov, 2023 Editor assigned by journal 07 Nov, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3573162","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":247568098,"identity":"76b6a27c-0a7f-4483-bf5f-a5e195a28422","order_by":0,"name":"Daniele Mannina","email":"data:image/png;base64,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","orcid":"","institution":"IRCCS Humanitas Research Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Daniele","middleName":"","lastName":"Mannina","suffix":""},{"id":247568099,"identity":"dd76e33d-cb22-488f-b45f-505a341e9f73","order_by":1,"name":"Stefania Bramanti","email":"","orcid":"https://orcid.org/0000-0002-4117-7991","institution":"Istituto Clinico Humanitas","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Stefania","middleName":"","lastName":"Bramanti","suffix":""},{"id":247568100,"identity":"43296380-208f-4aa1-b601-1de573c0bf81","order_by":2,"name":"Annalisa Chiappella","email":"","orcid":"https://orcid.org/0000-0002-2977-0098","institution":"Fondazione IRCSS Istituto Nazionale dei Tumori","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Annalisa","middleName":"","lastName":"Chiappella","suffix":""},{"id":247568101,"identity":"419e3172-a2c9-4cda-b808-07cd25d23c4d","order_by":3,"name":"Beatrice Casadei","email":"","orcid":"","institution":"IRCCS Azienda Ospedaliero-Universitaria di Bologna","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Beatrice","middleName":"","lastName":"Casadei","suffix":""},{"id":247568102,"identity":"2fc1ad4d-0b87-4866-b2dc-de7d19334e83","order_by":4,"name":"Chiara De Philippis","email":"","orcid":"https://orcid.org/0000-0002-7738-997X","institution":"Humanitas Clinical and Research Center – IRCCS","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chiara","middleName":"","lastName":"De Philippis","suffix":""},{"id":247568103,"identity":"d778abb7-f09e-4462-9ca8-d5daea2c5979","order_by":5,"name":"Laura Giordano","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Laura","middleName":"","lastName":"Giordano","suffix":""},{"id":247568104,"identity":"78c91c31-a20c-4020-83b3-fbc9139e0143","order_by":6,"name":"Pierina Navarria","email":"","orcid":"","institution":"IRCCS Humanitas Research Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Pierina","middleName":"","lastName":"Navarria","suffix":""},{"id":247568105,"identity":"a5c0363c-0b9a-48ca-84b0-4702effbe76c","order_by":7,"name":"Pietro Mancosu","email":"","orcid":"","institution":"Humanitas Clinical and Research Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Pietro","middleName":"","lastName":"Mancosu","suffix":""},{"id":247568106,"identity":"62f1b5f3-5618-44f5-a4c6-847de7934b60","order_by":8,"name":"Daniela Taurino","email":"","orcid":"","institution":"Humanitas Cancer Center","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Daniela","middleName":"","lastName":"Taurino","suffix":""},{"id":247568107,"identity":"7cc47670-a051-4abc-94da-f59cd5e80252","order_by":9,"name":"Marta Scorsetti","email":"","orcid":"","institution":"IRCCS Humanitas Research Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Marta","middleName":"","lastName":"Scorsetti","suffix":""},{"id":247568108,"identity":"8c9521f5-627c-48b9-ab22-d2f6f1dbbb80","order_by":10,"name":"Carmelo Carlo-Stella","email":"","orcid":"https://orcid.org/0000-0003-3144-0124","institution":"Humanitas Research Center - IRCCS","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Carmelo","middleName":"","lastName":"Carlo-Stella","suffix":""},{"id":247568109,"identity":"84d61c1d-1c24-4f8a-b1a4-5880b45857e2","order_by":11,"name":"Pier Luigi Zinzani","email":"","orcid":"https://orcid.org/0000-0002-2112-2651","institution":"University of Bologna","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Pier","middleName":"Luigi","lastName":"Zinzani","suffix":""},{"id":247568110,"identity":"b7d8b6c8-0424-4907-90c0-cc1cb8c63b0c","order_by":12,"name":"Armando Santoro","email":"","orcid":"","institution":"IRCCS Humanitas Research Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Armando","middleName":"","lastName":"Santoro","suffix":""},{"id":247568111,"identity":"7fca06b2-15b4-4b37-8ba9-7172fa26378a","order_by":13,"name":"Paolo Corradini","email":"","orcid":"https://orcid.org/0000-0002-9186-1353","institution":"Department of Oncology and Hemato-Oncology, University of Milan, Milan","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Paolo","middleName":"","lastName":"Corradini","suffix":""}],"badges":[],"createdAt":"2023-11-07 09:17:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3573162/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3573162/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41409-024-02427-8","type":"published","date":"2024-10-09T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":46804011,"identity":"b4e765e8-1e4a-4564-91de-215307312c0b","added_by":"auto","created_at":"2023-11-20 20:00:00","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":120664,"visible":true,"origin":"","legend":"\u003cp\u003eProgression-free survival by type of bridge.\u003c/p\u003e","description":"","filename":"Figure1OS.png","url":"https://assets-eu.researchsquare.com/files/rs-3573162/v1/1ad7ad561fa9247fc04dc5a2.png"},{"id":46804010,"identity":"79fa6a51-9be4-402f-a7d5-b193c6569c38","added_by":"auto","created_at":"2023-11-20 20:00:00","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":124081,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival by type of bridge.\u003c/p\u003e","description":"","filename":"Figure2PFS.png","url":"https://assets-eu.researchsquare.com/files/rs-3573162/v1/19dcfaca3d77ecf540241584.png"},{"id":66304517,"identity":"a3fbb653-c3fc-4e29-a620-d006f9a8f0d6","added_by":"auto","created_at":"2024-10-10 07:10:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1235093,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3573162/v1/9cbe1ae8-8a53-4be2-8e27-552ff761f371.pdf"}],"financialInterests":"The authors have declared there is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Role of bridging RT in relapsed/refractory diffuse large B-cell lymphoma undergoing CAR-T therapy: a multicenter study","fulltext":[{"header":"KEY POINTS","content":"\u003cul\u003e\n \u003cli\u003eIn relapsed/refractory diffuse large B-cell lymphoma, RT-based bridge can be associated with reduced drop-out rate and CAR-T toxicity.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003eAnti-CD19 chimeric antigen receptor (CAR)-T cell therapy is an effective treatment option for relapsed/refractory diffuse large B-cell lymphoma (DLBCL).\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e CAR-T manufacturing and delivery usually requires 3\u0026ndash;4 weeks. Because of the disease\u0026rsquo;s aggressive nature, in the period between lymphocyte collection and lymphodepleting chemotherapy (CT), DLBCL can be highly symptomatic or life-threatening, limiting the possibility of administering CAR-T infusion.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Therefore, a bridging regimen is required for most patients during the manufacturing of CAR-T to control disease progression and potentially reduce disease burden without adding toxicity, with the aim of bringing all the candidates to the CAR-T infusion. The bridging strategy is not standardized and ranges from steroids only to CT, targeted therapy, immunotherapy, or radiotherapy (RT).\u003csup\u003e\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e The efficacy of the bridging regimen can significantly impact the efficacy and toxicity of CAR-T treatment.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e Real-life registry data show that patients who do not need bridging therapy have a better outcome.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e Furthermore, a large disease volume is negatively associated with post-CAR-T progression-free survival (PFS) and is also a risk factor for cytokine-release syndrome (CRS).\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Therefore, strategy optimization for patients needing bridging therapy may be important to improve CAR-T efficacy and toxicity.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eCT-resistant, relapsed/refractory aggressive B-cell lymphomas may be sensitive to RT.\u003csup\u003e\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Preclinical data also suggest that RT can potentially enhance the efficacy of immunotherapy via antigen exposure (abscopal effect).\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e Moreover, using RT instead of drugs can minimize the impact on blood counts, organ function, and performance status of bridging therapy. However, comparative clinical data on RT versus CT as a bridging regimen to CAR-T are still scant.\u003c/p\u003e \u003cp\u003eBased on these premises, we retrospectively evaluated the potential impact of different bridging strategies in terms of efficacy and toxicity.\u003c/p\u003e"},{"header":"PATIENTS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSetting and design\u003c/h2\u003e \u003cp\u003eWe retrospectively collected consecutive patient candidates for CAR-T treatment for relapsed/refractory DLBCL from September 2019 to April 2022 in a real-life setting. The enrolment was multicentric, involving three Italian referral centers: IRCCS Humanitas Research Hospital (Rozzano, Italy), IRCCS Fondazione Istituto Nazionale dei Tumori (Milan, Italy), and Istituto Ser\u0026agrave;gnoli Policlinico Sant\u0026rsquo;Orsola, Bologna, Italy.\u003c/p\u003e \u003cp\u003e The protocol was written, and the study was conducted according to the International Guideline for Good Clinical Practice. The protocol and its annexes were approved by the competent Independent Ethics Committees (\u0026ldquo;IEC\u0026rdquo;) of the enrolling Centers (ONC/OSS-18/2021, ICH-3068).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eAll patients diagnosed with DLBCL relapsed or refractory to at least two lines of therapy who underwent leukapheresis for CAR-T manufacturing (tisagenlecleucel (tisa-cel), or axicabtagene ciloleucel (axi-cel)) were included. Patients receiving CAR-T treatment within an investigational study were excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eTreatment\u003c/h2\u003e \u003cp\u003eBridging therapy is defined as any treatment (CT, RT, steroids, other) administered from the date after the apheresis to the start of lymphodepleting therapy. All patients received a lymphodepleting regimen according to the standard guidelines for any CAR-T product. The decision to treat a patient with a bridging regimen was made in case of symptomatic or rapidly progressive disease. Among the patients needing a bridge, the criteria for choosing RT alone over a CT-containing regimen were the presence of localized disease or disseminated disease with a main symptomatic site. The cohort was divided into three groups: patients who did not receive any bridge (no-bridge group), patients who received RT-based bridge alone (RT group), and patients who received any other CT-based bridge (CT group).\u003c/p\u003e \u003cp\u003eAccording to Lugano criteria, disease evaluation with CT/PET scan was performed after bridging therapy and CAR-T therapy at day\u0026thinsp;+\u0026thinsp;30 and +\u0026thinsp;90 after infusion.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were diagnosed and classified according to autologous stem cell transplantation (ASTCT) criteria\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e and were managed according to local guidelines.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eObjective and endpoints\u003c/h2\u003e \u003cp\u003eThe study\u0026rsquo;s objective was to evaluate the outcome of all patients who were candidates for CAR-T treatment across the three groups. Firstly, we analyzed the direct response to bridging therapy in terms of the treatment\u0026rsquo;s ability to ensure disease control during the manufacturing period. Subsequently, we comparatively analyzed PFS (defined as the time from CAR-T infusion to disease progression, death, or loss to follow-up, whatever occurred first) and overall survival (OS; defined as the time from CAR-T infusion to death or loss to follow-up, whatever occurred first) after CAR-T infusion in the different groups. Other endpoints were the incidence of CRS, ICANS, and infections after CAR-T infusion.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData were summarized as frequencies and proportions or medians, and range and differences were estimated by the Chi-square test (the Fisher exact test when appropriate) for categorical variables. The Logistic regression methods were used to estimate the odds ratio and their corresponding 95% confidence intervals (CI) in univariate and multivariate analysis.\u003c/p\u003e \u003cp\u003eSurvival curves were estimated by the Kaplan-Meier method, and the log-rank test assessed the differences between groups. The multivariate Cox model was used to estimate the hazard ratio (HR) and their corresponding 95% CI. Statistical significance was set at 0.05 level.\u003c/p\u003e \u003cp\u003eAll analyses were performed using SAS version 9.4.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eWe enrolled 148 DLBCL patients (136 DLBCL, 12 transformed from low-grade B-cell lymphoma). Of them, 92 (62.2%) were males; the median age was 60 years (range 21\u0026ndash;73) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Most patients (60.1%) received two previous lines before CAR-T indication, 23.6% three previous lines, and 14.9% four or more lines. Only 14.2% had relapsed after responding to previous treatment, whereas most patients (85.8%) had a primary refractory disease. About one out of four patients (24.2%) had received ASCT. Double/triple-hit lymphoma was reported in 16.2% of cases.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient characteristics at baseline.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCT group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;84)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRT group (n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo-bridge group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eTotal\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(n\u0026thinsp;=\u0026thinsp;148)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCAR-T\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eInfused\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75\u003c/p\u003e \u003cp\u003e(89.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003cp\u003e(96.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26\u003c/p\u003e \u003cp\u003e(78.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e131\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(88.5%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eDead before infusion\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e(9.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e(15.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e14\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(9.5%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eAlive but not infused\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(6.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e3\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(2%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(range)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58\u003c/p\u003e \u003cp\u003e(21\u0026ndash;73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57\u003c/p\u003e \u003cp\u003e(21\u0026ndash;70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60\u003c/p\u003e \u003cp\u003e(29\u0026ndash;71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e58\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(21\u0026ndash;73)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.83\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eMale\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49\u003c/p\u003e \u003cp\u003e(58.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003cp\u003e(67.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22\u003c/p\u003e \u003cp\u003e(66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e92\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(62.2%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.54\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eFemale\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003cp\u003e(41.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e(32.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e(33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e56\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(37.8%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDiagnosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eDLBCL\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77\u003c/p\u003e \u003cp\u003e(91.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29\u003c/p\u003e \u003cp\u003e(93.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003cp\u003e(90.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e136\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(91.9%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;1 .00\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003et-DLBCL\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e12\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(8.1%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrevious lines\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e2\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003cp\u003e(59.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20\u003c/p\u003e \u003cp\u003e(64.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19\u003c/p\u003e \u003cp\u003e(57.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e89\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(60.1%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.44\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e3\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003cp\u003e(21.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e(25.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e(27.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e35\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(23.6%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e4\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e(10.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e(-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e10\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(6.7%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e5 or more\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(7.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(12.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e12\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(8.1%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eMissing\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(3.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e2\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(1.4%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDouble-hit phenotype\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eYes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003cp\u003e(14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e(32.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(6.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e24\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(16.2%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalicUnderline\" class=\"BoldItalicUnderline\" name=\"Emphasis\"\u003ep\u0026thinsp;=\u0026thinsp;0.02\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eNo\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72\u003c/p\u003e \u003cp\u003e(85.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003cp\u003e(67.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31\u003c/p\u003e \u003cp\u003e(93.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e124\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(83.8%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDouble-expressor phenotype\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eYes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003cp\u003e(26.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003cp\u003e(32.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e(27.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e41\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(27.7%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.84\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eNo\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41\u003c/p\u003e \u003cp\u003e(48.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003cp\u003e(45.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16\u003c/p\u003e \u003cp\u003e(8.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e71\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(48%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eNot available\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003cp\u003e(25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e(24.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e36\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(24.3%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStage at diagnosis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eI\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(4.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e(-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e4\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(2.7%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.55\u003c/em\u003e\u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eII\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003cp\u003e(16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e24\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(16.3%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eIII\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e(13.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(12.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e(24.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e23\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(15.4%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eIV\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003cp\u003e(65.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19\u003c/p\u003e \u003cp\u003e(61.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22\u003c/p\u003e \u003cp\u003e(66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e96\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(64.9%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eMissing\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e1\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(0.7)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRelapsed/refractory to last treatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eRelapsed\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e(13.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(12.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(18.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e21\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(14.2%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0 .76\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eRefractory\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73\u003c/p\u003e \u003cp\u003e(86.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27\u003c/p\u003e \u003cp\u003e(87.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27\u003c/p\u003e \u003cp\u003e(81.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e127\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(85.8%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePrior ASCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eYes\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003cp\u003e(22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003cp\u003e(38.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e(18.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e36\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(24.3%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0 .08\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eNo\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65\u003c/p\u003e \u003cp\u003e(77.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19\u003c/p\u003e \u003cp\u003e(61.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28\u003c/p\u003e \u003cp\u003e(81.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e112\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(75.7%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCAR-T product\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eTisa-cel\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61\u003c/p\u003e \u003cp\u003e(72.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003cp\u003e(48.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17\u003c/p\u003e \u003cp\u003e(51.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e93\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(62.8%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalicUnderline\" class=\"BoldItalicUnderline\" name=\"Emphasis\"\u003ep\u0026thinsp;=\u0026thinsp;0.02\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eAxi-cel\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003cp\u003e(27.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16\u003c/p\u003e \u003cp\u003e(51.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16\u003c/p\u003e \u003cp\u003e(48.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e55\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(37.2%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStage at leukapheresis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eI\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(2.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e(-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e4\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(2.7%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.77\u003c/em\u003e\u003csup\u003e\u003cb\u003e1\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eII\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003cp\u003e(16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e(16.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(18.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e25\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(16.9%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eIII\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13\u003c/p\u003e \u003cp\u003e(15.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(18.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e21\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(14.2%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eIV\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003cp\u003e(65.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003cp\u003e(70.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21\u003c/p\u003e \u003cp\u003e(63.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e98\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(66.2%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eApheresis-to-infusion time\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eMedian\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(range)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003cp\u003e(21\u0026ndash;96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49\u003c/p\u003e \u003cp\u003e(21\u0026ndash;96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e47\u003c/p\u003e \u003cp\u003e(30\u0026ndash;80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e41\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(31\u0026ndash;90)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eECOG performance status\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e0\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54\u003c/p\u003e \u003cp\u003e(64.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003cp\u003e(80.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003cp\u003e(75.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e104\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(70.3%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.17\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003e1\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003cp\u003e(35.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(19.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e(24.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003e44\u003c/em\u003e\u003c/p\u003e \u003cp\u003e\u003cem\u003e(29.7%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLDH at leukapheresis\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eIU/L\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e425\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e325\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e330\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e383\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.09\u003c/em\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLDH at lymphodepletion\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eIU/L\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e405\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e254\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e329\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e356\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.21\u003c/em\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ep value\u003c/em\u003e\u003csup\u003e\u003cem\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.42\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalicUnderline\" class=\"BoldItalicUnderline\" name=\"Emphasis\"\u003ep\u0026thinsp;=\u0026thinsp;0.05\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.84\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.22\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFerritin at leukapheresis\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003emg/dl\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e588\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e492\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e423\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e534\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.34\u003c/em\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFerritin at lymphodepletion mg/dl\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e734\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e713\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e750\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e733\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.97\u003c/em\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ep value\u003c/em\u003e\u003csup\u003e\u003cem\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.12\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.80\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalicUnderline\" class=\"BoldItalicUnderline\" name=\"Emphasis\"\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.49\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP at leukapheresis\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003emg/dl\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.09\u003c/em\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRP at lymphodepletion mg/dl\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eMean\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.21\u003c/em\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ep value\u003c/em\u003e\u003csup\u003e\u003cem\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.69\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.71\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalicUnderline\" class=\"BoldItalicUnderline\" name=\"Emphasis\"\u003ep\u0026thinsp;=\u0026thinsp;0.03\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e p value for III-IV vs I-II\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e paired t-test (pre-bridge vs post-bridge)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e t-test between bridge groups\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThirty-one patients were treated with RT alone, 33 did not receive any bridge (or received steroid-only), and 84 received various drug combinations (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). No differences across the study groups were disclosed in terms of baseline characteristics.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBridging strategies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eType of bridge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN of patients\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e\u003cb\u003eCT bridge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChemo-immunotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChemo-immunotherapy\u0026thinsp;+\u0026thinsp;local RT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLenalidomide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnti-CD3-CD20 bispecific andibody\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnti-CD19 immunoconjugate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e\u003cb\u003eRT bridge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle-site radiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean dose: 28 Gy (Range 17,5\u0026ndash;36 Gy)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean n. of fractions: 11 (range 5\u0026ndash;20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eAdministration of CAR-T infusion\u003c/h2\u003e \u003cp\u003eOf the 148 enrolled patients, 17 (11.5%) could not receive the infusion, and 131 (88.5%) underwent CAR-T therapy: 82 patients received tisa-cel and 49 axi-cel. CAR-T products were axi-cel for 37.2% of patients and tisa-cel for 62.8%.\u003c/p\u003e \u003cp\u003eThe reasons for not receiving CAR-T were disease progression in 12 of 17 cases (70.5%), COVID-19 infection in three of 17 cases (17.5%), psychiatric disturbance in one of 17 cases (6%); one patient was not infused because of complete remission (CR) after bridging therapy.\u003c/p\u003e \u003cp\u003eThe probability of receiving CAR-T infusion was 96.8% in the RT group (30/31), 89.2% in the CT group (75/84), and 78.8% in the no-bridge group (26/33), respectively (p\u0026thinsp;=\u0026thinsp;0.079). Mortality among patients who did not receive CAR-T infusion was 82% (14/17), and the cause was disease progression in 12/14 cases, Covid19 in 2/14 cases.\u003c/p\u003e \u003cp\u003eBefore CAR-T infusion, most patients (90%) in the no-bridge group (including steroid-only) showed disease progression. A disease evaluation after bridging therapy was available immediately before CAR-T infusion for 126 of 148 patients. Disease progression had a similar rate across the study groups (76.7% in the RT group, 73.7% in the CT group, and 90% in the no-bridge group; p\u0026thinsp;=\u0026thinsp;0.332). The analysis of biomarkers, such as LDH, ferritin, and C-reactive protein (CRP), showed no statistically significant difference across the bridge groups. We observed a significant decrease in LDH between leukapheresis and post-bridging time within the RT group and a significant increase in ferritin and CRP levels in the group not receiving any bridge (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eCAR-T efficacy\u003c/h2\u003e \u003cp\u003eAt day 30 after CAR-T infusion, CR was achieved in 43.5% of patients: 50% of patients in the RT group, 38.7% of those in the CT group, and 50% of those in the no-bridge group (p\u0026thinsp;=\u0026thinsp;0.469) [Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e]. At day 90 after CAR-T infusion, CR was reached in 53.2% of evaluable patients (n\u0026thinsp;=\u0026thinsp;109): 59.3% of patients in the RT group, 45.8% of those in the CT group, and 65.2% of those in the no-bridge group (p\u0026thinsp;=\u0026thinsp;0.218 for CR vs no CR).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eResponse at day 30 after CAR-T by group in 131 evaluable patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResponse\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCT group\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;75\u003c/p\u003e \u003cp\u003e(col %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRT group\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;30\u003c/p\u003e \u003cp\u003e(col %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo-bridge group\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;26\u003c/p\u003e \u003cp\u003e(col %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAll infused\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;131\u003c/p\u003e \u003cp\u003e(col %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29\u003c/p\u003e \u003cp\u003e(38.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003cp\u003e(50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003cp\u003e(50%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e57\u003c/p\u003e \u003cp\u003e(43.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003cp\u003e(20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(23.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(15.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e26\u003c/p\u003e \u003cp\u003e(19.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e(6.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(7.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e8\u003c/p\u003e \u003cp\u003e(6.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25\u003c/p\u003e \u003cp\u003e(33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(23.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(26.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e39\u003c/p\u003e \u003cp\u003e(29.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(0.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eP value for CR vs no CR: 0.469\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWith a median follow-up of 17 months from leukapheresis, the 1-year PFS and OS of the entire cohort were 37.6% and 63.6%, respectively. One-year PFS was 51.2% in the RT group, 28.2% in the CT group, and 47.6% in the no-bridge group, while 1-year OS was 86.7% in the RT group, 52.7% in the CT group, and 69% in the no-bridge group, respectively (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMultivariate analysis for factors associated with PFS and OS showed that the type of bridge (CT-based bridge vs RT-based bridge; p\u0026thinsp;=\u0026thinsp;0.025, p\u0026thinsp;=\u0026thinsp;0.044, respectively) and stage at leukapheresis (stage IV vs I\u0026ndash;III; p\u0026thinsp;=\u0026thinsp;0.003, p\u0026thinsp;=\u0026thinsp;0.014, respectively) were associated with poorer outcome (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Performance status was significantly associated only with OS (ECOG 1 vs 0; p\u0026thinsp;=\u0026thinsp;0.053) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). It should be considered that ECOG 2 before the CAR-T program, is an exclusion criterion of the Ministry of Health in Italy.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate models for progression-free survival (PFS) and overall survival (OS).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHazard ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eHazard Ratio (95% Confidence Limits)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003eOverall Survival\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo-bridge vs RT-based bridge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.391\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCT-based bridge vs RT-based bridge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStage at lymphodepletion IV vs I-III\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePerformance status 1 vs 0\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cspan type=\"BoldUnderline\" class=\"BoldUnderline\" name=\"Emphasis\"\u003eProgression-free Survival\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNO-bridge vs RT-based bridge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.521\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCT-based bridge vs RT-based bridge\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStage at lymphodepletion IV vs I-III\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eToxicity\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e shows the rate of infections, CRS, and ICANS after CAR-T. CRS occurred in 80.9% of the entire cohort (4.6%; grade 3\u0026ndash;4). CRS incidence was not different between the groups (p\u0026thinsp;=\u0026thinsp;0.92). ICANS occurred in 13.7% of patients. We observed a statistically significantly higher ICANS incidence in patients who received CT-based bridge than in others (20.0% in the CT group, 3.3% in the RT group, and 7.7% in the no-bridge group). In a multivariate model comparing RT with CT groups, axi-cel use (OR\u0026thinsp;=\u0026thinsp;42.4; 95% CI: 4.0\u0026ndash;447; p\u0026thinsp;=\u0026thinsp;0.004), baseline basal ECOG PS 1 (OR\u0026thinsp;=\u0026thinsp;33.3; 95% CI: 0.004\u0026ndash;0.3; p\u0026thinsp;=\u0026thinsp;0.004), and CT-based bridge use (OR\u0026thinsp;=\u0026thinsp;25.1; 95% CI: 1.8\u0026ndash;347.6; p\u0026thinsp;=\u0026thinsp;0.016) were confirmed as independent negative predictive factors for ICANS. We observed no association between the probability of ICANS and the disease stage at the time of leukapheresis.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eToxicity across the groups with different bridging therapy.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCT group\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;75\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRT group\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;30\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo-bridge group\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;26\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;131\u003c/p\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInfections\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003cp\u003e(20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(23.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(7.69%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e24\u003c/p\u003e \u003cp\u003e(18.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.273\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e60\u003c/p\u003e \u003cp\u003e(80%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003cp\u003e(83.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003cp\u003e(80.77%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e106\u003c/p\u003e \u003cp\u003e(80.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.926\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCRS G 3\u0026ndash;4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(5.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(3.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(3.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(4.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;1.00\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eICANS\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003cp\u003e(20%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(3.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(7.69%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e18\u003c/p\u003e \u003cp\u003e(13.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalicUnderline\" class=\"BoldItalicUnderline\" name=\"Emphasis\"\u003ep\u0026thinsp;=\u0026thinsp;0.056\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eICANS G3-4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(5.33%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e(-)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(3.85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e(3.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.823\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNRM\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(3.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(3.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(1.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.848\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003cem\u003eCRS\u0026thinsp;=\u0026thinsp;cytokine release syndrome; ICANS\u0026thinsp;=\u0026thinsp;immune effector cell associated neurotoxicity syndrome; NRM\u0026thinsp;=\u0026thinsp;non-relapse mortality events.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn the entire cohort, 18.3% of patients had at least one infectious complication; no difference in the incidence of infections was disclosed.\u003c/p\u003e \u003cp\u003eSix cases of non-relapse mortality were reported: one in the RT group (COVID-19), one in the no-bridge group (second tumor), and four in the CT group (one COVID-19, one septic shock, two severe neurotoxicity).\u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn the present study, we compared different bridging strategies on a large cohort of relapsed/refractory DLBCL adult patients who were candidates to receive tisa-cel or axi-cel in a real-life setting. The retrospective nature of the study and the selection bias of bridging strategy can affect the interpretation of our data, given that the bridging regimen has been selected for each patient according to disease characteristics and performance status. Nevertheless, homogeneous criteria for choosing RT bridging were adopted for the whole cohort, consisting in the presence of a prevalent bulky or symptomatic disease, independently from disease stage. In fact, no significant difference in baseline stage and LDH level was observed between the three groups, as shown in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. This finding suggests that the outcome may have not been directly determined by differences in disease distribution and burden.\u003c/p\u003e \u003cp\u003eThe first relevant finding of our study was the very low drop-out rate (3.2%) among patients treated with RT as a bridge, compared with those receiving a CT-based regimen (10.2%), but also compared with those receiving no bridging therapy (21.2%). Furthermore, our data showed a better outcome for patients not receiving bridging therapy in terms of OS and PFS. On the other hand, among the patients who needed a bridge, the outcome in terms of PFS and OS was more favorable for the RT group than the other regimens.\u003c/p\u003e \u003cp\u003eBridging success has been reported in previous real-world reports of DLBCL as strongly related to CAR-T outcome. In contrast, the advantage of RT seems unrelated to the direct response to the bridge.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Indeed, we observed no difference in bridging failure between the groups.\u003c/p\u003e \u003cp\u003eOur data are in line with a retrospective study previously published on axi-cel by Pinnix et al, which showed a better outcome for patients not needing a bridge or those undergoing RT-based bridge than those receiving CT-based bridge.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e The study\u0026rsquo;s authors speculatively attributed the poorer outcome to a higher disease burden in patients needing bridging therapy for disease control.\u003c/p\u003e \u003cp\u003eFurthermore, the study of Pinnix et al. included only patients treated with axi-cel, known to be more frequently associated with ICANS (up to 64% of treated patients),\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e and the authors did not report any difference in terms of CAR-T toxicity between the different bridging groups.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Differently, we reported a significantly lower rate of ICANS among patients in the RT group than in the CT group (1/31 vs 15/75), although the proportion of patients treated with axi-cel was higher in the RT group than in the CT group (16/31 vs 23/75). At multivariate analysis, RT-based bridge significantly reduced the risk of ICANS independently from the type of CAR-T and the Ann Arbor disease stage at the time of lymphodepletion. Considering one of the most well-grounded pathogenic mechanisms of ICANS onset,\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e it could be speculated that exposure to additional (poly-)CT cycles only a few weeks before CAR-T infusion may lead to a higher risk of neuroinflammation by increasing blood\u0026ndash;brain barrier (BBB) permeability\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e and facilitating the diffusion of proinflammatory cytokines in the brain; conversely, patients receiving RT regimen might be protected by ICANS. This study was not planned to verify this hypothesis; the prospective collection of biological data on BBB damage biomarkers before and after CAR-T infusion in the different bridging groups should be considered as a future project.\u003c/p\u003e \u003cp\u003eWe also found that only in the RT group could the LDH level be reduced by bridging, whereas we observed no improvement in inflammatory biomarkers in the other bridging group. Biomarkers, such as LDH, are related to both disease burden and inflammatory status; current evidence strongly suggests that inflammatory biomarkers are associated with CAR-T efficacy and toxicity.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Consistent with a previous report,\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e we hypothesize that RT has a lower impact on inflammation and endothelial damage than other bridging strategies and that this mechanism may explain the apparent lower toxicity of CAR-T after RT.\u003c/p\u003e \u003cp\u003eThe type of bridging therapy is only one of the multiple patients- and disease-related factors that can influence the final outcome of CAR-T, in addition to age, comorbidities, general conditions, disease volume, and systemic inflammatory status.\u003csup\u003e\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e Because of limitations arising from the retrospective nature of this study and the bias given by the non-randomized choice of bridging regimen, our findings cannot be conclusive in guiding the selection of the best bridge for each patient. Nonetheless, in our study, the type of bridging therapy was significantly associated with the drop-out rate and CAR-T toxicity. RT can be seen as an effective strategy to maximize the probability of receiving and then tolerating CAR-T infusion.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEditorial assistance was provided by Luca Giacomelli, PhD, Valentina Attanasio and Massimiliano Pianta; this assistance was supported by internal funds.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthorship contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSB, DM and AS designed the study. LG analysed the data. DM wrote the manuscript, with the revision and active contribution by SB, AS, PLZ and PC. CDP, DT, AC, BC, PN, MS, PM actively managed the patients and contributed in collecting the data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest disclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWestin JR, Kersten MJ, Salles G, et al. Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. Am J Hematol. 2021;96(10):1295\u0026ndash;1312.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbabneh HS, Abramson JS, Johnson PC, Patel CG. Assessing the role of radiotherapy in patients with refractory or relapsed high-grade B-cell lymphomas treated with CAR T-cell therapy. Radiother Oncol. 2022;175:65\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNastoupil LJ, Jain MD, Feng L, et al. Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium. J Clin Oncol. 2020;38(27):3119\u0026ndash;3128.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmini L, Silbert SK, Maude SL, et al. Preparing for CAR T cell therapy: patient selection, bridging therapies and lymphodepletion. Nat Rev Clin Oncol. 2022;19(5):342\u0026ndash;355.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSim AJ, Jain MD, Figura NB, et al. Radiation Therapy as a Bridging Strategy for CAR T Cell Therapy With Axicabtagene Ciloleucel in Diffuse Large B-Cell Lymphoma. Int J Radiat Oncol Biol Phys. 2019;105(5):1012\u0026ndash;1021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLocke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1\u0026ndash;2 trial. Lancet Oncol. 2019;20(1):31\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchuster SJ, Bishop MR, Tam CS, et al; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019;380(1):45\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBethge WA, Martus P, Schmitt M, et al. GLA/DRST real-world outcome analysis of CAR T-cell therapies for large B-cell lymphoma in Germany. Blood. 2022;140(4):349\u0026ndash;358.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFrey N. Cytokine release syndrome: Who is at risk and how to treat. Best Pract Res Clin Haematol. 2017;30(4):336\u0026ndash;340.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMartens C, Hodgson DC, Wells WA, et al. Outcome of hyperfractionated radiotherapy in chemotherapy-resistant non-Hodgkin's lymphoma. Int J Radiat Oncol Biol Phys. 2006;64(4):1183\u0026ndash;1187.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTseng YD, Chen YH, Catalano PJ, Ng A. Rates and durability of response to salvage radiation therapy among patients with refractory or relapsed aggressive non-Hodgkin lymphoma. Int J Radiat Oncol Biol Phys. 2015;91(1):223\u0026ndash;231.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim A, Stevenson P, Cassaday RD, et al. Impact of Double- or Triple-Hit Pathology on Rates and Durability of Radiation Therapy Response Among Patients With Relapsed or Refractory Large B-Cell Lymphoma. Pract Radiat Oncol. 2020;10(1):44\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDewey WC, Ling CC, Meyn RE. Radiation-induced apoptosis: relevance to radiotherapy. Int J Radiat Oncol Biol Phys. 1995;33(4):781\u0026ndash;796.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Y, Dong Y, Kong L, Shi F, Zhu H, Yu J. Abscopal effect of radiotherapy combined with immune checkpoint inhibitors. J Hematol Oncol. 2018;11(1):104.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheson BD, Fisher RI, Barrington SF, et al; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Espa\u0026ntilde;ol de M\u0026eacute;dula \u0026Oacute;sea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059\u0026ndash;3068.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee DW, Santomasso BD, Locke FL, et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019;25(4):625\u0026ndash;638.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBachy E, Le Gouill S, Di Blasi R, et al. A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma. Nat Med. 2022;28(10):2145\u0026ndash;2154.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePinnix CC, Gunther JR, Dabaja BS, et al. Bridging therapy prior to axicabtagene ciloleucel for relapsed/refractory large B-cell lymphoma. Blood Adv. 2020;4(13):2871\u0026ndash;2883.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017;377(26):2531\u0026ndash;2544.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGust J, Hay KA, Hanafi LA, et al. Endothelial Activation and Blood-Brain Barrier Disruption in Neurotoxicity after Adoptive Immunotherapy with CD19 CAR-T Cells. Cancer Discov. 2017;7(12):1404\u0026ndash;1419.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchultz L, Zurich MG, Culot M, et al. Evaluation of drug-induced neurotoxicity based on metabolomics, proteomics and electrical activity measurements in complementary CNS in vitro models. Toxicol In Vitro. 2015;30(1 Pt A):138\u0026ndash;165.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoussain C, Ricard D, Fike JR, Mazeron JJ, Psimaras D, Delattre JY. CNS complications of radiotherapy and chemotherapy. 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J Clin Oncol. 2020;38(27):3119\u0026ndash;3128.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhafouri S, Fenerty K, Schiller G, et al. Real-World Experience of Axicabtagene Ciloleucel and Tisagenlecleucel for Relapsed or Refractory Aggressive B-cell Lymphomas: A Single-Institution Experience. Clin Lymphoma Myeloma Leuk. 2021;21(12):861\u0026ndash;872.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bone-marrow-transplantation","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"bmt","sideBox":"Learn more about [Bone Marrow Transplantation](http://www.nature.com/bmt/)","snPcode":"41409","submissionUrl":"https://mts-bmt.nature.com/cgi-bin/main.plex","title":"Bone Marrow Transplantation","twitterHandle":"@bmtjournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3573162/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3573162/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe optimization of bridging regimen before chimeric antigen receptor (CAR)-T cell therapy in diffuse large B-cell lymphoma (DLBCL) may impact CAR-T efficacy and outcome. This retrospective study evaluates CAR-T outcome after bridging with radiotherapy (RT) and other bridging strategies. Among 148 patients with relapsed/refractory DLBCL who underwent leukapheresis for CAR-T manufacturing, 31 received RT-bridging, 84 chemotherapy (CT), 33 no-bridging or steroid-only. CAR-T cell were infused in 96.8% of RT-group. 89.2% of CT-group and 78.8% of no-bridge group (p = 0.079). Response to bridging was generally poor, but patients receiving RT had a significant reduction in LDH levels between pre- and post-bridging (p = 0.05). The one-year PFS was 51.2% in the RT group, 28.2% in the CT group, and 47.6% in the no-bridge group (p = 0.044); 1-year OS was 86.7% in the RT group, 52.7% in the CT group and 69% in the no-bridge group (p = 0.025). We observed a higher incidence of ICANS in patients who received CT than in others (20.0% CT group, 3.3% RT group, 7.7% no-bridge group; p = 0.05).\u003c/p\u003e\n\u003cp\u003eIn conclusion, RT-bridging is associated with lower drop-out rate and CAR-T toxicity, and it might be preferred to other bridging strategies for patients with localized disease or for those with one prevalent symptomatic site.\u003c/p\u003e","manuscriptTitle":"Role of bridging RT in relapsed/refractory diffuse large B-cell lymphoma undergoing CAR-T therapy: a multicenter study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-11-20 19:59:55","doi":"10.21203/rs.3.rs-3573162/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2023-12-15T14:32:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2023-12-09T03:46:33+00:00","index":1,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2023-12-04T05:30:51+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2023-11-22T23:48:00+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2023-11-18T15:47:31+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2023-11-17T17:37:23+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-11-09T10:41:05+00:00","index":"","fulltext":""},{"type":"submitted","content":"Bone Marrow Transplantation","date":"2023-11-08T12:02:49+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2023-11-08T11:25:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-11-07T09:13:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bone-marrow-transplantation","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"bmt","sideBox":"Learn more about [Bone Marrow Transplantation](http://www.nature.com/bmt/)","snPcode":"41409","submissionUrl":"https://mts-bmt.nature.com/cgi-bin/main.plex","title":"Bone Marrow Transplantation","twitterHandle":"@bmtjournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"276bf798-31e6-40e4-aacc-2e591ef17d95","owner":[],"postedDate":"November 20th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":26147097,"name":"Health sciences/Diseases/Cancer/Cancer therapy/Cancer immunotherapy"},{"id":26147098,"name":"Health sciences/Diseases/Cancer/Haematological cancer/Lymphoma/Non-hodgkin lymphoma/B-cell lymphoma"}],"tags":[],"updatedAt":"2024-10-10T07:10:33+00:00","versionOfRecord":{"articleIdentity":"rs-3573162","link":"https://doi.org/10.1038/s41409-024-02427-8","journal":{"identity":"bone-marrow-transplantation","isVorOnly":false,"title":"Bone Marrow Transplantation"},"publishedOn":"2024-10-09 04:00:00","publishedOnDateReadable":"October 9th, 2024"},"versionCreatedAt":"2023-11-20 19:59:55","video":"","vorDoi":"10.1038/s41409-024-02427-8","vorDoiUrl":"https://doi.org/10.1038/s41409-024-02427-8","workflowStages":[]},"version":"v1","identity":"rs-3573162","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3573162","identity":"rs-3573162","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}