Efficacy and Safety Analysis of CAR-T Cell Salvage Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma After Failure of Bispecific Antibody Treatment

Efficacy and Safety Analysis of CAR-T Cell Salvage Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma After Failure of Bispecific Antibody Treatment | 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 Research Article Efficacy and Safety Analysis of CAR-T Cell Salvage Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma After Failure of Bispecific Antibody Treatment Fuli Li, Henan Wang, Yuanzheng Liang, Xindi Liu, Jin Ye, Na Yao, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8473352/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Mar, 2026 Read the published version in Journal of Translational Medicine → Version 1 posted 4 You are reading this latest preprint version Abstract Background Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who failed bispecific antibody (BsAb) therapy face an extremely poor prognosis, necessitating exploration of effective salvage strategies. This study aimed to evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in this population. Methods We retrospectively enrolled 12 consecutive R/R DLBCL patients who received CAR-T therapy after BsAb failure at Beijing Tongren Hospital, Capital Medical University, between July 2023 and February 2025.Clinical data were reviewed to evaluate efficacy and safety outcomes. Results The 12 patients (M:F = 6:6) had a median age of 53 years (range: 34–65), a median IPI of 3 (range: 1–5), and with a median of 5 prior lines of therapy (range: 1–8). The majority (91.7%, 11/12) had ≥ 2 extranodal sites, and 25% (3/12) had bulky disease (> 7.5 cm). Prior to CAR-T, 33.3% (4/12) were bispecific antibody-relapsed and 66.7% (8/12) were bispecific antibody-refractory. BsAb targets included CD3/CD20 (n = 9; commercial glofitamab n = 7, investigational n = 2) and CD3/CD19 (n = 3, investigational). CAR-T products were CD19/CD22 dual-target (n = 10) and CD19 single-target (n = 2). The median washout period from last BsAb to lymphapheresis was 42 days (range: 8–172).With a median follow-up of 9.3 months (range: 5.3–14), the best overall response rate was 100% (complete response 50%, partial response 50%).Median progression-free survival (PFS) and overall survival (OS) were not reached. The Kaplan-Meier estimates showed 12-month PFS and OS rates were 54.5% and 50.5%, respectively.Cytokine release syndrome occurred in 83.3% (all grade 1–2) and ICANS in 8.3%(all grade 1). Hematologic toxicities were frequent, with grade ≥ 3 neutropenia (100%), anemia (33.3%), and thrombocytopenia (33.3%). Non-hematologic toxicities included grade 1 AST/ALT elevations (33.3%) and coagulation abnormalities (elevated D-dimer 41.7%; grade ≥ 3 hypofibrinogenemia 16.7%). All adverse events were manageable with standard interventions, and no treatment-related deaths occurred. Conclusion CAR-T salvage therapy demonstrated high response rates (ORR 100%) and manageable safety in BsAb R/R DLBCL patients. Early survival data suggest significant clinical benefit, though extended follow-up is needed to confirm durability. This study provides critical evidence supporting CAR-T as a preferred salvage strategy for BsAb-resistant patients. Diffuse large B-cell lymphoma Bispecific antibodies CAR-T cell therapy Salvage therapy Survival analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Diffuse large B-cell lymphoma (DLBCL), the most common aggressive non-Hodgkin lymphoma, is primarily treated with first-line R-CHOP therapy, though 30%-40% of patients develop relapsed/refractory (R/R) disease with poor prognosis[ 1 , 2 ]. T-cell redirection strategies have transformed R/R DLBCL treatment: CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy (e.g., axicabtagene ciloleucel, tisagenlecleucel) achieves ORRs of 53%-82% and CR rates of 53%-54% in pivotal trials[ 3 – 5 ], becoming a standard second-line + option, while bispecific antibodies (BsAbs, e.g., glofitamab, epcoritamab) act as "off-the-shelf" CD3/CD19/CD20-targeted agents with ORRs of 34%-53% and CR rates of 14%-30% in heavily pretreated patients, including 30% of CAR-T failures[ 6 – 7 ]. In contrast, clinical data on salvage CAR-T therapy after BsAb failure remain scarce. Shared antigen-dependent mechanisms, potential antigen loss/tumor microenvironment suppression post-BsAb, unclear optimal washout periods, and overlapping toxicities (e.g., cytokine release syndrome) raise critical concerns about subsequent CAR-T efficacy and safety[ 8 – 11 ]. With BsAbs increasingly used in earlier lines, investigating salvage CAR-T in BsAb-relapsed/refractory R/R DLBCL is vital. This retrospective study analyzed 12 such patients to evaluate response rates, survival, and safety, providing real-world evidence for this highly refractory population. Materials and Methods I. Materials Inclusion Criteria: Patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) treated in the Department of Hematology, Beijing Tongren Hospital, Capital Medical University, between July 2023 and February 2025 were retrospectively enrolled. Inclusion criteria were: ① Histopathologically confirmed LBCL (according to the 2016 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues); ②Prior bsAb treatment failure was defined as follows: bsAb-relapsed disease indicated loss of response after achieving a partial or complete response (PR/CR), while primary bsAb-refractory disease indicated failure to achieve at least a partial response (PR) at any point during treatment; ③ Receipt of chimeric antigen receptor T-cell (CAR-T) therapy; ④ Availability of complete clinical data for efficacy and safety assessment. Efficacy Evaluation:Efficacy was assessed according to the Lugano 2014 classification for lymphoma response criteria at 1 month, 3 months, 6 months post-CAR-T infusion, and subsequently every 3 months[ 12 – 14 ].We defined the best overall response rate as the proportion of patients achieving their best treatment response within 3 months, encompassing all response categories (including complete response and partial response).We defined PFS as the time from CAR-T cells infusion to disease progression or death from any cause.We defined OS as the time from CAR-T cell infusion to death from any cause. Adverse Event Management:Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were managed according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria (2019)[ 15 ]. Safety Evaluation:Adverse events (AEs) were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Incidence and severity (Grades 1–5) of hematologic toxicities (neutropenia, thrombocytopenia, anemia) and non-hematologic toxicities were recorded[ 16 ]. II. Statistical Analysis Statistical analysis was performed using R software.Descriptive Statistics: Continuous variables (e.g., age, number of prior lines, washout period, follow-up time) were described using median (range). Categorical variables (e.g., gender ratio, proportion with extranodal involvement, BsAb/CAR-T targets, response rates, AE incidence) were described using frequency counts and percentages.Survival Analysis:Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and survival curves were generated. The PFS and OS rates were reported with their 95% confidence intervals (CI) to reflect the statistical reliability of survival outcomes.All statistical analyses were based on the data from the 12 enrolled patients. Results I. Baseline Characteristics The summarized baseline characteristics and treatment history for the 12 patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), were as follows(Table 1 , 2 ):Demographics: Male-to-female ratio was 6(50%):6(50%); median age was 53 years (range: 34–65 years).Disease Characteristics: Eleven patients (91.7%) had ≥ 2 extranodal sites of involvement; 3 patients (25%) had bulky disease (> 7.5 cm);Median IPI was 3 (range, 1–5);median number of prior lines of therapy was 5 (range: 1–8).BsAb Therapy: Nine patients (75%) received CD3/CD20-targeting BsAbs (7 treated with glofitamab, 2 with an investigational agent); 3 patients (25%) received CD3/CD19-targeting BsAbs. 33.3%(4/12)were bispecific antibody-relapsed and 66.7%༈8/12༉were bispecific antibody-refractory. All 12 (100%) patients received bridging therapy, with outcomes as follows: 4 achieved partial response༈PR༉, 1 had progressive disease༈PD༉, 1 had stable disease༈SD༉, and 6 were not evaluated.The median washout period from the last BsAb dose to lymphapheresis was 42 days (range:8-172 days).The median time from lymphapheresis to infusion CAR-T cell was 17 days (range:11-73days).CAR-T Therapy: Ten patients (83.3%) received CD19/CD22 dual-target CAR-T cells;2 patients (16.7%) received CD19 single-target CAR-T cell therapy, both of whom were treated with academic CAR-T products. Table 1 Summary of Baseline Characteristics Characteristic All patinents, n (%) 12 (100) Sex, n (%) Male 6 (50) Female 6 (50) Age(years), n (%) > 60 4 (33.3) <=60 8 (66.7) Disease stage, n (%) Stage I-II 0 (0) Stage III-IV 12 (100) Pathological Features, n (%) GCB 5 (41.7) ABC 7 (58.3) IPI score, n (%) 2 10 (83.3) Extranodal sites =2 11 (91.7) Tumor Bulk (largest diamteter), n (%) >=7.5cm 3 (25) < 7.5cm 9 (75) Lines of therapy, n (%) 2 10 (83.3) Table 2 Individual Patient Clinical Characteristics Variables Gender Age Ann Arbor staging IPI Extranodal Sites Bulky Disease Prior Lines BsAb Target BsAb Best Response Pre-CAR-T Status Washout (days) CAR-T Target CAR-T Best Response Last Status PFS (m) OS (m) 1 M 48 4 3 7 No 8 CD3/CD20 PD Refractory 90 CD19 PR Died 2.0 10.1 2 F 61 3 3 1 No 5 CD3/CD20 PD Refractory 35 CD19 CR Died 6.0 10.9 3 M 51 4 1 3 No 5 CD3/CD19 PD Refractory 172 CD19/CD22 CR Alive 1.0 14.0 4 F 55 4 4 4 Yes 5 CD3/CD19 PD Refractory 154 CD19/CD22 PR Alive 12.4 12.4 5 F 61 4 4 4 No 2 CD3/CD20 PD Refractory 22 CD19/CD22 CR Alive 10.3 10.3 6 M 56 4 3 2 No 5 CD3/CD20 PR relapsed 49 CD19/CD22 PR Alive 10.2 10.2 7 M 47 4 3 2 No 7 CD3/CD20 PD Refractory 99 CD19/CD22 PR Died 5.6 5.6 8 F 45 4 2 2 No 1 CD3/CD20 CR relapsed 63 CD19/CD22 CR Alive 8.4 8.4 9 F 48 4 3 2 No 7 CD3/CD20 PD Refractory 15 CD19/CD22 CR Alive 7.6 7.6 10 F 62 3 3 4 No 3 CD3/CD19 PR relapsed 8 CD19/CD22 CR Alive 6.5 6.5 11 M 34 4 4 4 Yes 5 CD3/CD20 PD Refractory 13 CD19/CD22 PR Alive 4.3 6.1 12 M 65 4 5 3 Yes 4 CD3/CD20 PR relapsed 20 CD19/CD22 PR Alive 5.3 5.3 II. Efficacy All patients achieved an objective response, yielding a best objective response rate (ORR) of 100%. Six patients (50%) achieved a complete response (CR), and 6 patients (50%) achieved a partial response (PR).The median follow-up duration was 9.3 months.Median PFS and OS were not reached. Kaplan-Meier estimates showed 12-month PFS and OS rates of 54.5% and 50.5%, respectively (Fig. 1). At the 1-month post-CAR-T response assessment, 75% (9/12) of patients commenced maintenance therapy, which primarily included PD-1 inhibitors (88.9%), XPO1 inhibitors (66.7%), HDAC inhibitors (11.1%), BKT inhibitors (11.1%), and a CD30-directed antibody-drug conjugate (11.1%).The survival outcomes were illustrated with distinct response patterns and event statuses among patients(Fig. 2). III. Safety Cytokine Release Syndrome (CRS): Ten patients (83.3%) experienced grade 1–2 CRS. No grade ≥ 3 CRS events occurred.Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): One patient (8.3%) experienced grade 1 ICANS. No grade ≥ 3 ICANS events occurred.Hematologic and laboratory toxicities were prominent. Grade ≥ 3 hematologic toxicities were universal, including neutropenia in all 12 patients (100%), with concurrent febrile neutropenia in 8 (66.7%), as well as thrombocytopenia and anemia each in 4 patients (33.3%). Among non-hematologic toxicities, grade 1 elevations in AST or ALT were observed in 4 patients (33.3%). Coagulation abnormalities were also noted, with D-dimer levels exceeding 2×ULN in 5 patients (41.7%) and grade ≥ 3 hypofibrinogenemia in 2 patients (16.7%).No unexpected adverse events occurred(Table 3 ). Table 3 Safety Safety Events N = 12(100%) CRS (Grade 1–2); no ≥ Grade 3 10 (83.3%) ICANS (Grade 1); no ≥ Grade 3 1 (8.3%) hematologic toxicities Grade ≥ 3 Neutropenia 12 (100%) febrile neutropenia 8 (66.7%) Grade ≥ 3 Thrombocytopenia 4 (33.3%) Grade ≥ 3 Anemia 4 (33.3%) non-hematologic toxicities grade 1 elevations in AST or ALT 4 (33.3%) D-dimer levels exceeding 2×ULN 5(41.7%) grade ≥ 3 hypofibrinogenemia 2(16.7%) IV. The impact of bispecific antibody efficacy on CAR-T therapy This study enrolled a total of 12 patients who received CAR-T cell therapy. Based on their response status to prior bispecific antibody (bsAb) treatment before CAR-T infusion, they were stratified into two groups: the bsAb-relapsed group (Group A, n = 4, 33.3%) and the bsAb-refractory group (Group B, n = 8, 66.7%). Efficacy evaluation revealed that the best overall response rate (ORR) after CAR-T therapy reached 100% in both groups, with identical depth of response: complete response (CR) rates were 50% and partial response (PR) rates were 50% in each group, indicating excellent and comparable initial therapeutic efficacy.Survival outcome analysis demonstrated no statistically significant differences in progression-free survival (PFS) or overall survival (OS) between the two groups. The comparative results for PFS were: hazard ratio (HR) = 0.4297, P = 0.3553; and for OS: HR = 0.2717, P = 0.4493 (both P > 0.05)(Fig. 3). V. The impact of bispecific antibody washout time on CAR-T therapy This study utilized a median washout period of 42 days as the cutoff value to stratify subjects into Group A (washout period 42 days), aiming to analyze the impact of washout duration on treatment efficacy. Regarding the best response to CAR-T therapy, the objective response rate (ORR) reached 100% in both groups. Specifically, Group A achieved a complete response (CR) rate of 66.7% and a partial response (PR) rate of 33.3%, while Group B showed a CR rate of 33.3% and a PR rate of 66.7%.Analysis of survival outcomes demonstrated no statistically significant differences between the groups. For progression-free survival (PFS), the hazard ratio (HR) was 1.203 (P = 0.8374); for overall survival (OS), the HR was 0.8394 (P = 0.8842)(Fig. 4). Discussion Despite the extremely poor prognosis of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) patients failing bispecific antibody (BsAb) therapy and the paucity of data on subsequent salvage strategies, our study provides valuable evidence for chimeric antigen receptor T-cell (CAR-T) therapy. With a 100% overall response rate (50% complete response, 50% partial response) and manageable safety profiles (predominantly grade 1–2 adverse events without treatment-related deaths), CAR-T emerges as a promising salvage option for this high-risk population. Current CAR-T therapy demonstrates superior efficacy and safety in R/R large B-cell lymphomas compared to three landmark trials (ZUMA-1, TRANSCEND NHL 001, JULIET)[ 4 , 5 , 17 ]. All 12 patients achieved ORR (100%), including 50% CR and 50% PR—surpassing ZUMA-1 (82% ORR), TRANSCEND NHL 001 (73% ORR), and JULIET (52% ORR). Median PFS and OS were not reached; 12-month PFS and OS rates were 54.5% and 50.5%, exceeding ZUMA-1 (5.8-month median PFS; 52% 18-month OS), TRANSCEND NHL 001 (6.8-month median PFS; 58% 12-month OS), and JULIET (12-month median OS). Safety was favorable: 83.3% had grade 1 CRS (no ≥ grade 3, vs. 13%, 2%, and 22% ≥grade 3 in the trials) and 8.3% had grade 1 ICANS (no ≥ grade 3, vs. 28%, 10%, and 12%).All 12 patients (100%) had grade ≥ 3 neutropenia—higher than classic trials (78% in ZUMA-1, 60% in TRANSCEND NHL 001, 34% [any grade] in JULIET)—but grade ≥ 3 thrombocytopenia (33.3%) and anemia (33.3%) were comparable to or lower than those studies (e.g., 38% and 43% for ≥ 3 grade thrombocytopenia and anemia in ZUMA-1, respectively). The most compelling explanation provided is the distinct antigen targeting. Most patients received CD20/CD3 BsAbs followed by CD19 or CD19/CD22-directed CAR T-cells. Resistance to BsAbs, potentially through CD20 downregulation or loss, does not impair the ability of CD19/CD22-targeting CAR T-cells to recognize and eliminate tumor cells. This demonstrates a lack of overlapping antigen escape mechanisms.The study infers that the mechanisms leading to BsAb failure (e.g., transient T-cell exhaustion, pharmacokinetic issues) may not permanently damage the endogenous T-cell repertoire to the extent that it compromises the manufacture or function of a completely new, genetically engineered, and ex vivo expanded CAR T-cell product. CAR-T therapy demonstrated consistent and robust efficacy in 12 patients with prior bsAb exposure, regardless of whether they were bsAb-relapsed (Group A, n = 4, 33.3%) or bsAb-refractory (Group B, n = 8, 66.7%). Both groups achieved 100% ORR with identical response depth (50% CR, 50% PR). No significant differences were observed in PFS (HR = 0.4297, P = 0.3553) or OS (HR = 0.2717, P = 0.4493), confirming prior bsAb failure pattern does not affect long-term CAR-T outcomes.The clinical data shows nearly identical response rates to CAR T-cells between prior BsAb responders and non-responders. This key finding strongly suggests that the factors causing primary resistance to BsAbs (e.g., the tumor microenvironment, insufficient native T-cell activation) are effectively bypassed or overcome by the unique properties of CAR T-cells.CAR T-cells are potent, autologous "live drugs" that are less dependent on the patient's immediate immune status at the time of infusion compared to a continuously administered biologic like a BsAb. In this study of 12 patients stratified by a 42-day washout cutoff (Group A: 42 days, n = 6), both groups achieved 100% ORR. Group A showed a higher CR rate (66.7% vs. 33.3%) and lower PR rate (33.3% vs. 66.7%). Survival outcomes were comparable: PFS HR = 1.203 (P = 0.8374) and OS HR = 0.8394 (P = 0.8842), indicating no significant impact of washout duration on long-term efficacy.The 42-day washout period far exceeds 5–6 half-lives based on the glofitamab half-life of 6–11 days[ 18 ], which was sufficient to facilitate near-complete drug clearance.Our analysis hypothesized that this drug-free interval may provide a window for the recovery of T-cell fitness, as continuous BsAb exposure had been associated with T-cell exhaustion. The washout period was thus thought to provide a critical window for endogenous T-cells to recover from an activated/exhausted state, with the aim of yielding a higher-quality T-cell population for apheresis and subsequent CAR-T product manufacturing. This finding aligns remarkably with the data from the retrospective multicenter study by Crochet et al. (2024) published in Blood, which evaluated 47 patients with relapsed/refractory large B-cell lymphoma (R/R LBCL) who received CD19-targeted CAR-T therapy after prior exposure to BsAbs (primarily CD20/CD3 BsAbs, with 91% of patients exposed to this subtype). In this study, the best ORR and CR rate to subsequent CAR-T therapy reached 85% and 43%, respectively. Notably, when compared with a 1:1 propensity score-matched (PSM) control group of 42 BsAb-naïve patients who received axi-cel or tisagenlecleucel, the BsAb-pretreated group demonstrated a higher ORR (86% vs. 55%; P = .02), while CR rate (43% vs. 38%; P = .5), 1-year PFS (42% vs. 29%; P = .13), and 1-year OS (55% vs. 37%; P = .08) were comparable. This indicates that prior BsAb exposure not only did not impair CAR-T efficacy but also was associated with superior objective response rates in subsequent CAR-T therapy, a trend consistent with the aforementioned current study[ 19 ].​ Although limited by a modest sample size (n = 12) and a relatively short follow-up—and considering that CAR-T was administered as an investigational product in clinical trials whereas BsAb treatment was not exclusively trial-based—our study suggested that prior resistance to BsAbs did not appear to preclude a subsequent robust response to CAR-T therapy.Both BsAb-relapsed and BsAb-refractory patients achieved a remarkable 100% ORR, with no significant differences in survival outcomes. These findings indicate that the mechanisms of resistance to BsAbs may not inherently cross-impair the function of subsequently administered CAR T-cells, highlighting a potential asymmetric resistance profile between these two immunotherapies. Conclusion Our small-sample retrospective study preliminarily indicates that salvage CAR-T therapy demonstrates favorable efficacy and safety in DLBCL patients who have failed prior bispecific antibody treatment. While these initial findings are promising, long-term follow-up and larger prospective studies are warranted for further validation. Declarations Patient consent for publication Consent obtained directly from patients. Ethics approval The Institutional Review Board of Beijing Tongren Hospital approved the study (TREC2022-KY103) and we conducted the study in accordance with the Declaration of Helsinki. Informed consent from patients was obtained. Contributors Data acquisition: FL, HW, YL,XL, JYe, NY, LYang,YW and JC. Data analysis and interpretation: FL and JC. Statistical analysis: FL and JC. Manuscript preparation: FL and JC. Manuscript editing: FL, JYe, NY and LYang. Manuscript review: JC and LW. All authors read and approved the final article. LW is the guarantor of the study. Competing interests None declared. Provenance and peer review Not commissioned; externally peer reviewed. Fundings This work was supported by grants from National Science and Technology Major Project of China (2025ZD0544300) and the National Natural Science Foundation of China (Nos. 82170181 and 82370188) to LW. Data availability statement The data supporting the findings of this study are available from the corresponding authors (Liang Wang or Jia Cong) upon reasonable request, in accordance with the ethical approval and patient privacy regulations of Beijing Tongren Hospital. References Sabattini E et al. WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview. Pathologica vol. 102,3 (2010): 83 – 7. Poletto S, et al. Treatment strategies for patients with diffuse large B-cell lymphoma. Cancer Treat Rev. 2022;110:102443. Lamure S et al. 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New Engl J Med vol. 2019;380(1):45–56. Minson A, Dickinson M. Glofitamab CD20-TCB bispecific antibody. Leuk lymphoma vol. 2021;62(13):3098–108. Crochet G, et al. Efficacy of CAR T-cell therapy is not impaired by previous bispecific antibody treatment in large B-cell lymphoma. Blood vol. 2024;144(3):334–3381. Cite Share Download PDF Status: Published Journal Publication published 19 Mar, 2026 Read the published version in Journal of Translational Medicine → Version 1 posted Reviewers agreed at journal 09 Feb, 2026 Reviewers invited by journal 08 Feb, 2026 Editor assigned by journal 22 Jan, 2026 First submitted to journal 21 Jan, 2026 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-8473352","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":587769536,"identity":"708b7b73-7a86-429a-ac18-803b8d261e00","order_by":0,"name":"Fuli Li","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYBACNvnnBx8kGEjwsDEzAxkVNYS18DHkJBt8qLCR42NnSzZ4cOYYYS1yDAlmkjPOpBnL8fOYST5sYSbCYQwHEqR52w4ntjGzpVUkNrAx8Ld3J+DXwth4wBiihfnYjcQdMgwSZ85uwK+FmSEhGWbLjcQzbAwGErkEtADVHIZo4TErAJJEaOFhMGwEeZ8NqIWBOC0SPMkMoEBmY2ZLlkg4c4yHoF/kZ7Af/wGKSvn+wwc//qiokeNv78WvBQPwkKZ8FIyCUTAKRgFWAACJ40TDt3b6ewAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0009-0001-6835-103X","institution":"Beijing Tongren Hospital CMU","correspondingAuthor":true,"prefix":"","firstName":"Fuli","middleName":"","lastName":"Li","suffix":""},{"id":587769537,"identity":"bc07051d-dba8-479c-9643-ca70066094ba","order_by":1,"name":"Henan Wang","email":"","orcid":"","institution":"Beijing Tongren Hospital 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CMU","correspondingAuthor":false,"prefix":"","firstName":"Jin","middleName":"","lastName":"Ye","suffix":""},{"id":587769541,"identity":"d7260ab5-b643-4988-b108-fb289b541d91","order_by":5,"name":"Na Yao","email":"","orcid":"","institution":"Beijing Tongren Hospital CMU","correspondingAuthor":false,"prefix":"","firstName":"Na","middleName":"","lastName":"Yao","suffix":""},{"id":587769542,"identity":"f7a13173-8b57-4388-acac-d375e02540f9","order_by":6,"name":"Lei Yang","email":"","orcid":"","institution":"Beijing Tongren Hospital CMU","correspondingAuthor":false,"prefix":"","firstName":"Lei","middleName":"","lastName":"Yang","suffix":""},{"id":587769543,"identity":"acfd0eaf-4eb8-4891-95e4-bec3212725b2","order_by":7,"name":"Yiping Wu","email":"","orcid":"","institution":"Beijing Tongren Hospital CMU","correspondingAuthor":false,"prefix":"","firstName":"Yiping","middleName":"","lastName":"Wu","suffix":""},{"id":587769544,"identity":"f38f7a29-0eb5-4404-a765-801165de0ad4","order_by":8,"name":"Liang Wang","email":"","orcid":"https://orcid.org/0000-0001-6140-914X","institution":"Beijing Tongren Hospital CMU","correspondingAuthor":false,"prefix":"","firstName":"Liang","middleName":"","lastName":"Wang","suffix":""},{"id":587769545,"identity":"c8210b4f-b833-4d97-b9fb-19dfb81606df","order_by":9,"name":"Jia Cong","email":"","orcid":"https://orcid.org/0000-0002-5001-6575","institution":"Beijing Tongren Hospital CMU","correspondingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"Cong","suffix":""}],"badges":[],"createdAt":"2025-12-29 13:14:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8473352/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8473352/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12967-026-08035-y","type":"published","date":"2026-03-19T15:59:18+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":102746561,"identity":"a85e1ca6-c4a7-4b84-927f-fca7b427bb3a","added_by":"auto","created_at":"2026-02-16 08:58:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":20164,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8473352/v1/3a6165f34a08b2d5af2b2dd7.png"},{"id":102538103,"identity":"07030994-1463-499b-ba3b-07e5f3dd1a9b","added_by":"auto","created_at":"2026-02-12 17:59:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":59638,"visible":true,"origin":"","legend":"\u003cp\u003eThe survival outcomes were illustrated with distinct response patterns and event statuses among patients.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8473352/v1/af6bd0e1680a818277bf7d1b.png"},{"id":102538101,"identity":"8a644ff1-d6a1-4e17-a9c2-a4da59c633e7","added_by":"auto","created_at":"2026-02-12 17:59:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":26165,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8473352/v1/13b9613225058cbd55f1d056.png"},{"id":102538104,"identity":"542a5846-2141-4dd8-98a9-7f032004abe8","added_by":"auto","created_at":"2026-02-12 17:59:57","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":21282,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8473352/v1/3df8ac130e09e22de70dfe26.png"},{"id":105224142,"identity":"11657e57-1f84-47ae-9f88-38f2a6cb2de8","added_by":"auto","created_at":"2026-03-23 16:12:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":838166,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8473352/v1/02d16a14-7e83-4013-a8e9-ce25d2a5adb4.pdf"}],"financialInterests":"","formattedTitle":"Efficacy and Safety Analysis of CAR-T Cell Salvage Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma After Failure of Bispecific Antibody Treatment","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDiffuse large B-cell lymphoma (DLBCL), the most common aggressive non-Hodgkin lymphoma, is primarily treated with first-line R-CHOP therapy, though 30%-40% of patients develop relapsed/refractory (R/R) disease with poor prognosis[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. T-cell redirection strategies have transformed R/R DLBCL treatment: CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy (e.g., axicabtagene ciloleucel, tisagenlecleucel) achieves ORRs of 53%-82% and CR rates of 53%-54% in pivotal trials[\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], becoming a standard second-line\u0026thinsp;+\u0026thinsp;option, while bispecific antibodies (BsAbs, e.g., glofitamab, epcoritamab) act as \"off-the-shelf\" CD3/CD19/CD20-targeted agents with ORRs of 34%-53% and CR rates of 14%-30% in heavily pretreated patients, including 30% of CAR-T failures[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In contrast, clinical data on salvage CAR-T therapy after BsAb failure remain scarce. Shared antigen-dependent mechanisms, potential antigen loss/tumor microenvironment suppression post-BsAb, unclear optimal washout periods, and overlapping toxicities (e.g., cytokine release syndrome) raise critical concerns about subsequent CAR-T efficacy and safety[\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. With BsAbs increasingly used in earlier lines, investigating salvage CAR-T in BsAb-relapsed/refractory R/R DLBCL is vital. This retrospective study analyzed 12 such patients to evaluate response rates, survival, and safety, providing real-world evidence for this highly refractory population.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\n\u003ch3\u003eI. Materials\u003c/h3\u003e\n\u003cp\u003eInclusion Criteria:\u003c/p\u003e\u003cp\u003ePatients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL) treated in the Department of Hematology, Beijing Tongren Hospital, Capital Medical University, between July 2023 and February 2025 were retrospectively enrolled. Inclusion criteria were: ① Histopathologically confirmed LBCL (according to the 2016 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues); ②Prior bsAb treatment failure was defined as follows: bsAb-relapsed disease indicated loss of response after achieving a partial or complete response (PR/CR), while primary bsAb-refractory disease indicated failure to achieve at least a partial response (PR) at any point during treatment; ③ Receipt of chimeric antigen receptor T-cell (CAR-T) therapy; ④ Availability of complete clinical data for efficacy and safety assessment.\u003c/p\u003e \u003cp\u003eEfficacy Evaluation:Efficacy was assessed according to the Lugano 2014 classification for lymphoma response criteria at 1 month, 3 months, 6 months post-CAR-T infusion, and subsequently every 3 months[\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].We defined the best overall response rate as the proportion of patients achieving their best treatment response within 3 months, encompassing all response categories (including complete response and partial response).We defined PFS as the time from CAR-T cells infusion to disease progression or death from any cause.We defined OS as the time from CAR-T cell infusion to death from any cause.\u003c/p\u003e \u003cp\u003eAdverse Event Management:Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were managed according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria (2019)[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSafety Evaluation:Adverse events (AEs) were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Incidence and severity (Grades 1\u0026ndash;5) of hematologic toxicities (neutropenia, thrombocytopenia, anemia) and non-hematologic toxicities were recorded[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eII. Statistical Analysis\u003c/h3\u003e\n\u003cp\u003eStatistical analysis was performed using R software.Descriptive Statistics: Continuous variables (e.g., age, number of prior lines, washout period, follow-up time) were described using median (range). Categorical variables (e.g., gender ratio, proportion with extranodal involvement, BsAb/CAR-T targets, response rates, AE incidence) were described using frequency counts and percentages.Survival Analysis:Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and survival curves were generated. The PFS and OS rates were reported with their 95% confidence intervals (CI) to reflect the statistical reliability of survival outcomes.All statistical analyses were based on the data from the 12 enrolled patients.\u003c/p\u003e"},{"header":"Results","content":"\n\u003ch3\u003eI. Baseline Characteristics\u003c/h3\u003e\n\u003cp\u003eThe summarized baseline characteristics and treatment history for the 12 patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), were as follows(Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e,\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e):Demographics: Male-to-female ratio was 6(50%):6(50%); median age was 53 years (range: 34\u0026ndash;65 years).Disease Characteristics: Eleven patients (91.7%) had\u0026thinsp;\u0026ge;\u0026thinsp;2 extranodal sites of involvement; 3 patients (25%) had bulky disease (\u0026gt;\u0026thinsp;7.5 cm);Median IPI was 3 (range, 1\u0026ndash;5);median number of prior lines of therapy was 5 (range: 1\u0026ndash;8).BsAb Therapy: Nine patients (75%) received CD3/CD20-targeting BsAbs (7 treated with glofitamab, 2 with an investigational agent); 3 patients (25%) received CD3/CD19-targeting BsAbs. 33.3%(4/12)were bispecific antibody-relapsed and 66.7%༈8/12༉were bispecific antibody-refractory. All 12 (100%) patients received bridging therapy, with outcomes as follows: 4 achieved partial response༈PR༉, 1 had progressive disease༈PD༉, 1 had stable disease༈SD༉, and 6 were not evaluated.The median washout period from the last BsAb dose to lymphapheresis was 42 days (range:8-172 days).The median time from lymphapheresis to infusion CAR-T cell was 17 days (range:11-73days).CAR-T Therapy: Ten patients (83.3%) received CD19/CD22 dual-target CAR-T cells;2 patients (16.7%) received CD19 single-target CAR-T cell therapy, both of whom were treated with academic CAR-T products.\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\u003eSummary of Baseline Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll patinents, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(years), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (33.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;=60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (66.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease stage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage I-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStage III-IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathological Features, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGCB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (41.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eABC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (58.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIPI score, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;=2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (16.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (83.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtranodal sites\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;=2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (91.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor Bulk (largest diamteter), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;=7.5cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;7.5cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLines of therapy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;=2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (16.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (83.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \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\u003eIndividual Patient Clinical Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"17\"\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 \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=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c17\" colnum=\"17\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnn Arbor staging\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIPI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eExtranodal Sites\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBulky Disease\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003ePrior Lines\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eBsAb Target\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eBsAb Best Response\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003ePre-CAR-T Status\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eWashout\u003c/p\u003e \u003cp\u003e(days)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCAR-T Target\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCAR-T Best Response\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c15\"\u003e \u003cp\u003eLast Status\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c16\"\u003e \u003cp\u003ePFS\u003c/p\u003e \u003cp\u003e(m)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c17\"\u003e \u003cp\u003eOS\u003c/p\u003e \u003cp\u003e(m)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCD3/CD20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRefractory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCD19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eDied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e10.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCD3/CD20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRefractory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCD19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eDied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e6.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e10.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCD3/CD19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRefractory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e172\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCD19/CD22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e14.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCD3/CD19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRefractory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e154\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCD19/CD22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e12.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e12.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCD3/CD20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRefractory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCD19/CD22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e10.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e10.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCD3/CD20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003erelapsed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCD19/CD22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e10.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e10.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCD3/CD20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRefractory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCD19/CD22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eDied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e5.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCD3/CD20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003erelapsed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCD19/CD22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e8.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e8.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCD3/CD20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRefractory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCD19/CD22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e7.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e7.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCD3/CD19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003erelapsed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCD19/CD22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCD3/CD20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eRefractory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCD19/CD22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eCD3/CD20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003erelapsed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c12\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eCD19/CD22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c16\"\u003e \u003cp\u003e5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c17\"\u003e \u003cp\u003e5.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eII. Efficacy\u003c/h3\u003e\n\u003cp\u003eAll patients achieved an objective response, yielding a best objective response rate (ORR) of 100%. Six patients (50%) achieved a complete response (CR), and 6 patients (50%) achieved a partial response (PR).The median follow-up duration was 9.3 months.Median PFS and OS were not reached. Kaplan-Meier estimates showed 12-month PFS and OS rates of 54.5% and 50.5%, respectively (Fig.\u0026nbsp;1). At the 1-month post-CAR-T response assessment, 75% (9/12) of patients commenced maintenance therapy, which primarily included PD-1 inhibitors (88.9%), XPO1 inhibitors (66.7%), HDAC inhibitors (11.1%), BKT inhibitors (11.1%), and a CD30-directed antibody-drug conjugate (11.1%).The survival outcomes were illustrated with distinct response patterns and event statuses among patients(Fig.\u0026nbsp;2).\u003c/p\u003e\n\u003ch3\u003eIII. Safety\u003c/h3\u003e\n\u003cp\u003eCytokine Release Syndrome (CRS): Ten patients (83.3%) experienced grade 1\u0026ndash;2 CRS. No grade\u0026thinsp;\u0026ge;\u0026thinsp;3 CRS events occurred.Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): One patient (8.3%) experienced grade 1 ICANS. No grade\u0026thinsp;\u0026ge;\u0026thinsp;3 ICANS events occurred.Hematologic and laboratory toxicities were prominent. Grade\u0026thinsp;\u0026ge;\u0026thinsp;3 hematologic toxicities were universal, including neutropenia in all 12 patients (100%), with concurrent febrile neutropenia in 8 (66.7%), as well as thrombocytopenia and anemia each in 4 patients (33.3%). Among non-hematologic toxicities, grade 1 elevations in AST or ALT were observed in 4 patients (33.3%). Coagulation abnormalities were also noted, with D-dimer levels exceeding 2\u0026times;ULN in 5 patients (41.7%) and grade\u0026thinsp;\u0026ge;\u0026thinsp;3 hypofibrinogenemia in 2 patients (16.7%).No unexpected adverse events occurred(Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\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\u003eSafety\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSafety Events\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;12(100%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRS (Grade 1\u0026ndash;2); no\u0026thinsp;\u0026ge;\u0026thinsp;Grade 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (83.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICANS (Grade 1); no\u0026thinsp;\u0026ge;\u0026thinsp;Grade 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ehematologic toxicities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade\u0026thinsp;\u0026ge;\u0026thinsp;3 Neutropenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003efebrile neutropenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade\u0026thinsp;\u0026ge;\u0026thinsp;3 Thrombocytopenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrade\u0026thinsp;\u0026ge;\u0026thinsp;3 Anemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enon-hematologic toxicities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003egrade 1 elevations in AST or ALT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (33.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD-dimer levels exceeding 2\u0026times;ULN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(41.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003egrade\u0026thinsp;\u0026ge;\u0026thinsp;3 hypofibrinogenemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(16.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eIV. The impact of bispecific antibody efficacy on CAR-T therapy\u003c/h3\u003e\n\u003cp\u003eThis study enrolled a total of 12 patients who received CAR-T cell therapy. Based on their response status to prior bispecific antibody (bsAb) treatment before CAR-T infusion, they were stratified into two groups: the bsAb-relapsed group (Group A, n\u0026thinsp;=\u0026thinsp;4, 33.3%) and the bsAb-refractory group (Group B, n\u0026thinsp;=\u0026thinsp;8, 66.7%). Efficacy evaluation revealed that the best overall response rate (ORR) after CAR-T therapy reached 100% in both groups, with identical depth of response: complete response (CR) rates were 50% and partial response (PR) rates were 50% in each group, indicating excellent and comparable initial therapeutic efficacy.Survival outcome analysis demonstrated no statistically significant differences in progression-free survival (PFS) or overall survival (OS) between the two groups. The comparative results for PFS were: hazard ratio (HR)\u0026thinsp;=\u0026thinsp;0.4297, P\u0026thinsp;=\u0026thinsp;0.3553; and for OS: HR\u0026thinsp;=\u0026thinsp;0.2717, P\u0026thinsp;=\u0026thinsp;0.4493 (both P\u0026thinsp;\u0026gt;\u0026thinsp;0.05)(Fig.\u0026nbsp;3).\u003c/p\u003e\n\u003ch3\u003eV. The impact of bispecific antibody washout time on CAR-T therapy\u003c/h3\u003e\n\u003cp\u003eThis study utilized a median washout period of 42 days as the cutoff value to stratify subjects into Group A (washout period\u0026thinsp;\u0026lt;\u0026thinsp;42 days) and Group B (washout period\u0026thinsp;\u0026gt;\u0026thinsp;42 days), aiming to analyze the impact of washout duration on treatment efficacy. Regarding the best response to CAR-T therapy, the objective response rate (ORR) reached 100% in both groups. Specifically, Group A achieved a complete response (CR) rate of 66.7% and a partial response (PR) rate of 33.3%, while Group B showed a CR rate of 33.3% and a PR rate of 66.7%.Analysis of survival outcomes demonstrated no statistically significant differences between the groups. For progression-free survival (PFS), the hazard ratio (HR) was 1.203 (P\u0026thinsp;=\u0026thinsp;0.8374); for overall survival (OS), the HR was 0.8394 (P\u0026thinsp;=\u0026thinsp;0.8842)(Fig.\u0026nbsp;4).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDespite the extremely poor prognosis of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) patients failing bispecific antibody (BsAb) therapy and the paucity of data on subsequent salvage strategies, our study provides valuable evidence for chimeric antigen receptor T-cell (CAR-T) therapy. With a 100% overall response rate (50% complete response, 50% partial response) and manageable safety profiles (predominantly grade 1\u0026ndash;2 adverse events without treatment-related deaths), CAR-T emerges as a promising salvage option for this high-risk population.\u003c/p\u003e \u003cp\u003eCurrent CAR-T therapy demonstrates superior efficacy and safety in R/R large B-cell lymphomas compared to three landmark trials (ZUMA-1, TRANSCEND NHL 001, JULIET)[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. All 12 patients achieved ORR (100%), including 50% CR and 50% PR\u0026mdash;surpassing ZUMA-1 (82% ORR), TRANSCEND NHL 001 (73% ORR), and JULIET (52% ORR). Median PFS and OS were not reached; 12-month PFS and OS rates were 54.5% and 50.5%, exceeding ZUMA-1 (5.8-month median PFS; 52% 18-month OS), TRANSCEND NHL 001 (6.8-month median PFS; 58% 12-month OS), and JULIET (12-month median OS). Safety was favorable: 83.3% had grade 1 CRS (no\u0026thinsp;\u0026ge;\u0026thinsp;grade 3, vs. 13%, 2%, and 22% \u0026ge;grade 3 in the trials) and 8.3% had grade 1 ICANS (no\u0026thinsp;\u0026ge;\u0026thinsp;grade 3, vs. 28%, 10%, and 12%).All 12 patients (100%) had grade\u0026thinsp;\u0026ge;\u0026thinsp;3 neutropenia\u0026mdash;higher than classic trials (78% in ZUMA-1, 60% in TRANSCEND NHL 001, 34% [any grade] in JULIET)\u0026mdash;but grade\u0026thinsp;\u0026ge;\u0026thinsp;3 thrombocytopenia (33.3%) and anemia (33.3%) were comparable to or lower than those studies (e.g., 38% and 43% for \u0026ge;\u0026thinsp;3 grade thrombocytopenia and anemia in ZUMA-1, respectively). The most compelling explanation provided is the distinct antigen targeting. Most patients received CD20/CD3 BsAbs followed by CD19 or CD19/CD22-directed CAR T-cells. Resistance to BsAbs, potentially through CD20 downregulation or loss, does not impair the ability of CD19/CD22-targeting CAR T-cells to recognize and eliminate tumor cells. This demonstrates a lack of overlapping antigen escape mechanisms.The study infers that the mechanisms leading to BsAb failure (e.g., transient T-cell exhaustion, pharmacokinetic issues) may not permanently damage the endogenous T-cell repertoire to the extent that it compromises the manufacture or function of a completely new, genetically engineered, and ex vivo expanded CAR T-cell product.\u003c/p\u003e \u003cp\u003eCAR-T therapy demonstrated consistent and robust efficacy in 12 patients with prior bsAb exposure, regardless of whether they were bsAb-relapsed (Group A, n\u0026thinsp;=\u0026thinsp;4, 33.3%) or bsAb-refractory (Group B, n\u0026thinsp;=\u0026thinsp;8, 66.7%). Both groups achieved 100% ORR with identical response depth (50% CR, 50% PR). No significant differences were observed in PFS (HR\u0026thinsp;=\u0026thinsp;0.4297, P\u0026thinsp;=\u0026thinsp;0.3553) or OS (HR\u0026thinsp;=\u0026thinsp;0.2717, P\u0026thinsp;=\u0026thinsp;0.4493), confirming prior bsAb failure pattern does not affect long-term CAR-T outcomes.The clinical data shows nearly identical response rates to CAR T-cells between prior BsAb responders and non-responders. This key finding strongly suggests that the factors causing primary resistance to BsAbs (e.g., the tumor microenvironment, insufficient native T-cell activation) are effectively bypassed or overcome by the unique properties of CAR T-cells.CAR T-cells are potent, autologous \"live drugs\" that are less dependent on the patient's immediate immune status at the time of infusion compared to a continuously administered biologic like a BsAb.\u003c/p\u003e \u003cp\u003eIn this study of 12 patients stratified by a 42-day washout cutoff (Group A: \u0026lt;42 days, n\u0026thinsp;=\u0026thinsp;6; Group B: \u0026gt;42 days, n\u0026thinsp;=\u0026thinsp;6), both groups achieved 100% ORR. Group A showed a higher CR rate (66.7% vs. 33.3%) and lower PR rate (33.3% vs. 66.7%). Survival outcomes were comparable: PFS HR\u0026thinsp;=\u0026thinsp;1.203 (P\u0026thinsp;=\u0026thinsp;0.8374) and OS HR\u0026thinsp;=\u0026thinsp;0.8394 (P\u0026thinsp;=\u0026thinsp;0.8842), indicating no significant impact of washout duration on long-term efficacy.The 42-day washout period far exceeds 5\u0026ndash;6 half-lives based on the glofitamab half-life of 6\u0026ndash;11 days[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], which was sufficient to facilitate near-complete drug clearance.Our analysis hypothesized that this drug-free interval may provide a window for the recovery of T-cell fitness, as continuous BsAb exposure had been associated with T-cell exhaustion. The washout period was thus thought to provide a critical window for endogenous T-cells to recover from an activated/exhausted state, with the aim of yielding a higher-quality T-cell population for apheresis and subsequent CAR-T product manufacturing.\u003c/p\u003e \u003cp\u003eThis finding aligns remarkably with the data from the retrospective multicenter study by Crochet et al. (2024) published in Blood, which evaluated 47 patients with relapsed/refractory large B-cell lymphoma (R/R LBCL) who received CD19-targeted CAR-T therapy after prior exposure to BsAbs (primarily CD20/CD3 BsAbs, with 91% of patients exposed to this subtype). In this study, the best ORR and CR rate to subsequent CAR-T therapy reached 85% and 43%, respectively. Notably, when compared with a 1:1 propensity score-matched (PSM) control group of 42 BsAb-na\u0026iuml;ve patients who received axi-cel or tisagenlecleucel, the BsAb-pretreated group demonstrated a higher ORR (86% vs. 55%; P\u0026thinsp;=\u0026thinsp;.02), while CR rate (43% vs. 38%; P\u0026thinsp;=\u0026thinsp;.5), 1-year PFS (42% vs. 29%; P\u0026thinsp;=\u0026thinsp;.13), and 1-year OS (55% vs. 37%; P\u0026thinsp;=\u0026thinsp;.08) were comparable. This indicates that prior BsAb exposure not only did not impair CAR-T efficacy but also was associated with superior objective response rates in subsequent CAR-T therapy, a trend consistent with the aforementioned current study[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].​\u003c/p\u003e \u003cp\u003eAlthough limited by a modest sample size (n\u0026thinsp;=\u0026thinsp;12) and a relatively short follow-up\u0026mdash;and considering that CAR-T was administered as an investigational product in clinical trials whereas BsAb treatment was not exclusively trial-based\u0026mdash;our study suggested that prior resistance to BsAbs did not appear to preclude a subsequent robust response to CAR-T therapy.Both BsAb-relapsed and BsAb-refractory patients achieved a remarkable 100% ORR, with no significant differences in survival outcomes. These findings indicate that the mechanisms of resistance to BsAbs may not inherently cross-impair the function of subsequently administered CAR T-cells, highlighting a potential asymmetric resistance profile between these two immunotherapies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur small-sample retrospective study preliminarily indicates that salvage CAR-T therapy demonstrates favorable efficacy and safety in DLBCL patients who have failed prior bispecific antibody treatment. While these initial findings are promising, long-term follow-up and larger prospective studies are warranted for further validation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cb\u003e Patient consent for publication\u003c/b\u003e\u003c/p\u003e \u003cp\u003eConsent obtained directly from patients.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics approval\u003c/strong\u003e \u003cp\u003e The Institutional Review Board of Beijing Tongren Hospital approved the study (TREC2022-KY103) and we conducted the study in accordance with the Declaration of Helsinki. Informed consent from patients was obtained.\u003c/p\u003e \u003ch2\u003eContributors\u003c/h2\u003e \u003cp\u003eData acquisition: FL, HW, YL,XL, JYe, NY, LYang,YW and JC. Data analysis and interpretation: FL and JC. Statistical analysis: FL and JC. Manuscript preparation: FL and JC. Manuscript editing: FL, JYe, NY and LYang. Manuscript review: JC and LW. All authors read and approved the final article. LW is the guarantor of the study.\u003c/p\u003e \u003ch2\u003eCompeting interests\u003c/h2\u003e \u003cp\u003eNone declared.\u003c/p\u003e \u003ch2\u003eProvenance and peer review\u003c/h2\u003e \u003cp\u003eNot commissioned; externally peer reviewed.\u003c/p\u003e \u003ch2\u003eFundings\u003c/h2\u003e \u003cp\u003eThis work was supported by grants from National Science and Technology Major Project of China (2025ZD0544300) and the National Natural Science Foundation of China (Nos. 82170181 and 82370188) to LW.\u003c/p\u003e\u003ch2\u003eData availability statement\u003c/h2\u003e \u003cp\u003e The data supporting the findings of this study are available from the corresponding authors (Liang Wang or Jia Cong) upon reasonable request, in accordance with the ethical approval and patient privacy regulations of Beijing Tongren Hospital.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSabattini E et al. WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview. Pathologica vol. 102,3 (2010): 83\u0026thinsp;\u0026ndash;\u0026thinsp;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePoletto S, et al. Treatment strategies for patients with diffuse large B-cell lymphoma. Cancer Treat Rev. 2022;110:102443.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLamure S et al. Clinical and Product Features Associated with Outcome of DLBCL Patients to CD19-Targeted CAR T-Cell Therapy. Cancers 13,17 4279. 25 Aug. 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbramson JS et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet (London, England) vol. 396,10254 (2020): 839\u0026ndash;852.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNeelapu, Sattva S, et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. New Engl J Med vol. 2017;377(26):2531\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrooks TR et al. Jul. Real-world outcomes of patients with aggressive B-cell lymphoma treated with epcoritamab or glofitamab. Blood, blood.2025029117. 15 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGurion R, et al. Efficacy and safety of Glofitamab in patients with R/R DLBCL in real life setting- a retrospective study. Annals Hematol vol. 2025;104(7):3821\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFarhat M et al. Sep. From R-CHOP to revolution: How CAR T-Cells, ADCs, and bispecific antibodies are transforming DLBCL treatment. Crit Rev Oncol/Hematol, 215 104917. 1 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim J, Kim SJ. Advances in T-Cell-Directed Immunotherapy for Adult Mature B-Cell Lymphoma: A Comprehensive Review of CAR T-Cell and Bispecific Antibody Therapies. Cancer Res Treat vol. 2025;57(4):905\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrinkmann BJ, et al. CD20-bispecific antibodies improve response to CD19-CAR T cells in lymphoma in vitro and CLL in vivo models. Blood vol. 2024;144(7):784\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchipani M et al. Oct. Bispecific Monoclonal Antibodies in Diffuse Large B-Cell Lymphoma: Dawn of a New Era in Targeted Therapy. Cancers vol. 17,19 3258. 8 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCheson BD et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin oncology: official J Am Soc Clin Oncol 32,27 (2014): 3059\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarrington SF et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the International Conference on Malignant Lymphomas Imaging Working Group. Journal of clinical oncology: official journal of the American Society of Clinical Oncology vol. 32,27 (2014): 3048-58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrganizing Committee of the Lugano Classification Workshop. Current Status of Revisions to the Lugano Classification in Lymphoma. Hematol Oncol vol. 2025;43(4):e70103.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee DW et al. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 25,4 (2019): 625\u0026ndash;38.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFreites-Martinez A et al. Using the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0) to Evaluate the Severity of Adverse Events of Anticancer Therapies. CTCAE versi\u0026oacute;n 5.0. Evaluaci\u0026oacute;n de la gravedad de los eventos adversos dermatol\u0026oacute;gicos de las terapias antineopl\u0026aacute;sicas. Actas dermo-sifiliograficas vol. 112,1 (2021): 90\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchuster SJ, et al. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. New Engl J Med vol. 2019;380(1):45\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMinson A, Dickinson M. Glofitamab CD20-TCB bispecific antibody. Leuk lymphoma vol. 2021;62(13):3098\u0026ndash;108.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCrochet G, et al. Efficacy of CAR T-cell therapy is not impaired by previous bispecific antibody treatment in large B-cell lymphoma. Blood vol. 2024;144(3):334\u0026ndash;3381.\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":"journal-of-translational-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jtrm","sideBox":"Learn more about [Journal of Translational Medicine](http://translational-medicine.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/jtrm/default.aspx","title":"Journal of Translational Medicine","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Diffuse large B-cell lymphoma, Bispecific antibodies, CAR-T cell therapy, Salvage therapy, Survival analysis","lastPublishedDoi":"10.21203/rs.3.rs-8473352/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8473352/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePatients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who failed bispecific antibody (BsAb) therapy face an extremely poor prognosis, necessitating exploration of effective salvage strategies. This study aimed to evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in this population.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e We retrospectively enrolled 12 consecutive R/R DLBCL patients who received CAR-T therapy after BsAb failure at Beijing Tongren Hospital, Capital Medical University, between July 2023 and February 2025.Clinical data were reviewed to evaluate efficacy and safety outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe 12 patients (M:F\u0026thinsp;=\u0026thinsp;6:6) had a median age of 53 years (range: 34\u0026ndash;65), a median IPI of 3 (range: 1\u0026ndash;5), and with a median of 5 prior lines of therapy (range: 1\u0026ndash;8). The majority (91.7%, 11/12) had\u0026thinsp;\u0026ge;\u0026thinsp;2 extranodal sites, and 25% (3/12) had bulky disease (\u0026gt;\u0026thinsp;7.5 cm). Prior to CAR-T, 33.3% (4/12) were bispecific antibody-relapsed and 66.7% (8/12) were bispecific antibody-refractory. BsAb targets included CD3/CD20 (n\u0026thinsp;=\u0026thinsp;9; commercial glofitamab n\u0026thinsp;=\u0026thinsp;7, investigational n\u0026thinsp;=\u0026thinsp;2) and CD3/CD19 (n\u0026thinsp;=\u0026thinsp;3, investigational). CAR-T products were CD19/CD22 dual-target (n\u0026thinsp;=\u0026thinsp;10) and CD19 single-target (n\u0026thinsp;=\u0026thinsp;2). The median washout period from last BsAb to lymphapheresis was 42 days (range: 8\u0026ndash;172).With a median follow-up of 9.3 months (range: 5.3\u0026ndash;14), the best overall response rate was 100% (complete response 50%, partial response 50%).Median progression-free survival (PFS) and overall survival (OS) were not reached. The Kaplan-Meier estimates showed 12-month PFS and OS rates were 54.5% and 50.5%, respectively.Cytokine release syndrome occurred in 83.3% (all grade 1\u0026ndash;2) and ICANS in 8.3%(all grade 1). Hematologic toxicities were frequent, with grade\u0026thinsp;\u0026ge;\u0026thinsp;3 neutropenia (100%), anemia (33.3%), and thrombocytopenia (33.3%). Non-hematologic toxicities included grade 1 AST/ALT elevations (33.3%) and coagulation abnormalities (elevated D-dimer 41.7%; grade\u0026thinsp;\u0026ge;\u0026thinsp;3 hypofibrinogenemia 16.7%). All adverse events were manageable with standard interventions, and no treatment-related deaths occurred.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eCAR-T salvage therapy demonstrated high response rates (ORR 100%) and manageable safety in BsAb R/R DLBCL patients. Early survival data suggest significant clinical benefit, though extended follow-up is needed to confirm durability. This study provides critical evidence supporting CAR-T as a preferred salvage strategy for BsAb-resistant patients.\u003c/p\u003e","manuscriptTitle":"Efficacy and Safety Analysis of CAR-T Cell Salvage Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma After Failure of Bispecific Antibody Treatment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-12 17:59:46","doi":"10.21203/rs.3.rs-8473352/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2026-02-09T15:09:57+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-08T16:58:04+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-23T02:13:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Translational Medicine","date":"2026-01-21T08:23:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-translational-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jtrm","sideBox":"Learn more about [Journal of Translational Medicine](http://translational-medicine.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/jtrm/default.aspx","title":"Journal of Translational Medicine","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8a900ce5-8c20-4109-b339-b99a8d332ab2","owner":[],"postedDate":"February 12th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-23T16:09:09+00:00","versionOfRecord":{"articleIdentity":"rs-8473352","link":"https://doi.org/10.1186/s12967-026-08035-y","journal":{"identity":"journal-of-translational-medicine","isVorOnly":false,"title":"Journal of Translational Medicine"},"publishedOn":"2026-03-19 15:59:18","publishedOnDateReadable":"March 19th, 2026"},"versionCreatedAt":"2026-02-12 17:59:46","video":"","vorDoi":"10.1186/s12967-026-08035-y","vorDoiUrl":"https://doi.org/10.1186/s12967-026-08035-y","workflowStages":[]},"version":"v1","identity":"rs-8473352","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8473352","identity":"rs-8473352","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}