Bendamustine Plus Rituximab Versus R-Minichop as First-Line Treatment in Unfit Patients with Diffuse Large B-Cell Lymphoma

Bendamustine Plus Rituximab Versus R-Minichop as First-Line Treatment in Unfit Patients with Diffuse Large B-Cell Lymphoma | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Bendamustine Plus Rituximab Versus R-Minichop as First-Line Treatment in Unfit Patients with Diffuse Large B-Cell Lymphoma Dongdong Zhang, Tao Liu, Natasha Kaweme, Youhong Dong, Liling Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-580186/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective : To evaluate the efficacy and safety of bendamustine plus rituximab (BR) and low-does CHOP chemotherapy regimen-rituximab combination (R-miniCHOP) in elderly patients with diffuse large-B cell lymphoma, unfit for full dose immunochemotherapy. Method : Patients over 70 years with diffuse larger B-cell lymphoma or follicular lymphoma grade 3B, defined as unfit according to Comprehensive Geriatric Assessment (CGA), were included in our study. BR or R-miniCHOP was individualized according to the patients’ performance status and the presence of comorbidities. All the patients were received 4-6 cycles of immunochemotherapy at three-week intervals. Objective remission rate and adverse reaction were evaluated between the two groups. Result: This study included thirty-two patients enrolled between January 2020 and November 2020. The median age was 74 years (range 70-82). Twelve patients received BR, whereas twenty patients were treated with R-miniCHOP. The objective remission rate in the BR group was a slightly higher than the R-miniCHOP group (83.3% vs 75%), but with no statistical significance ( P = 0.581). Furthermore, the objective remission rate was influenced by a serum beta 2 microglobulin concentration of 3 mg/L or less. The BR group showed a lower incidence of leukopenia than the R-miniCHOP group ( P = 0.029), but had a higher incidence of fever ( P = 0.036). Conclusion: BR showed equivalent efficacy but more improved safety in unfit patients with diffuse large-B cell lymphoma compared to R-miniCHOP. BR should be considered as an alternative treatment in this subgroup of patients. Oncology Diffuse large-B cell lymphoma Bendamustine plus rituximab R-miniCHOP Unfit Objective remission rate. Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, with 40% incidence in patients age over 70 years old [ 1 ]. The chimeric anti-CD20 monoclonal antibody rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy (R-CHOP) has dramatically improved the overall survival in patients with DLBCL in the last two decades. R-CHOP was recommended as a standard treatment for patients with DLBCL by the Groupe d’Etudes des Lymphomes de l’Adulte (GELA), depending on patients’ age. Full dose R-CHOP was initially preferred in adult patients and elderly patients aged 60–80 [ 2 , 3 ]. An attenuated immunochemotherapy regimen, R-miniCHOP, was identified and showed favorable efficacy and safety in patients over 80 years old [ 4 ]. However, the presence of comorbidities and concomitant infections often led to reduced tolerability to treatment-related toxicities, resulting in treatment discontinuation and treatment failure in older patients [ 5 ]. In lymphoma, the cut-off age 65 was defined as a watershed between younger and older patients [ 6 ]. The R-miniCHOP regimen recommended by GELA for the treatment of DLBCL is also based on whether the patients is 80 years or older. Nevertheless, treatment should be individualized while incorporating individual life expectancy, functional reserve and social support into consideration [ 7 ]. A complete comprehensive geriatric assessment (CGA) should be undertaken to determine if older patients can tolerate intensive therapy with curative intent. CGA divides older patients into three categories: fit, unfit and frail, according to age, comorbidities and functional abilities of daily living [ 8 ]. CGA has proved to be an efficacy tool to identify fit patients who can benefit from intensive curative approach [ 9 ]. To date, there are few studies on therapeutic regimens applied in unfit patients except R-miniCHOP. Previously, studies had shown that treatment failure of R-miniCHOP in older patients (> 80) with DLBCL was associated with treatment-related toxicities and pre-existing medical comorbidities other than advanced age and relatively-low dose intensity [ 5 ]. Thus, more efficacious and low-toxicity regimens need to be exploited. Bendamustine is a unique bifunctional alkylating agent with antimetabolic properties and antitumor effects [ 10 ]. The rebirth of bendamustine was in that it exhibited synergistic antitumor effects combined with rituximab (BR) for the treatment of lymphoid malignancies [ 11 , 12 ]. Previous clinical trials reported that BR improved survival outcome in indolent non-Hodgkin lymphoma (NHL) and relapsed/refractory DLBCL patients [ 13 , 14 ]. There are currently limited clinical data available to rationalize therapeutic regimens for unfit patients with newly diagnosed DLBCL. A prospective phase II study showed anti-CD20 monoclonal antibody obinutuzumab plus CHOP was efficacious and safe for treating unfit patients with DLBCL [ 15 ]. Recently, a phase II clinical trial demonstrated that the BR regimen was a promising first-line treatment for frail patients with DLBCL due to its promising activity and manageable toxicity profile [ 16 ]. There is no prospective study comparing BR and R-miniCHOP as frontline treatment in unfit patients at present. Our study investigated the efficacy, safety, toxicity profile, and overall remission rate (ORR) of BR compared to R-miniCHOP as first-line treatment in unfit patients with newly diagnosed DLBCL or follicular lymphoma (FL) grade 3B in China. Materials And Methods Study design and patient eligibility FL grade 3B is closely related to DLBCL and may transform to DLBCL. Therefore, the standard treatment regimens used in FL grade 3B are similar to that of DLBCL in routine clinical practice [17]. In this study, patients newly diagnosed with DLBCL or FL grade 3B were enrolled from January 2020 to December 2020. Diagnosis of DLBCL or FL grade 3B based on histopathologic morphology, immunohistology and clinical feature recommended by WHO 2016 [18]. Patients were classified as unfit according to simple CGA. Table 1 illustrates the inclusion criteria for this study [9]. Patients considered to be unfit included in this study met the following criteria: (a) Age≥70; (b) White blood cells≥3.0×10 9 /L or granulocytes ≥1.5×10 9 /L, hemoglobin≥90.0×10 12 /L, platelets≥100×10 9 /L; (c) Normal sinus rhythm, ejection fraction 50-70% on echocardiography; (d) ALT and AST levels below the 2×upper limit of normal, serum albumin≥30.0 g/L, serum creatinine below the 1.5×upper limit of normal; (e) HIV/AIDS negative. Clinical staging was based on modified Lugano 2014 staging criteria. The risk stratification was identified using International Prognostic Index (IPI). All the patients were received at least 2 cycles of R-miniCHOP or BR, depending on patients’ performance status and the presence of comorbidities. Clinical features of R-miniCHOP and BR regimens are summarized in Table 2. In patients presenting with potential worsening cardiac function, doxorubicin was replaced by the liposome Adriamycin. This study was approved by the Ethics and Scientific Committee of Union Hospital of Tongji Medical College, Huazhong University of Science and Technology with approval number 2020211. All the patients were given written informed consent before immunochemotherapy and the data were collected from electronic medical record of Union hospital, Tongji Medical college. Response evaluation Treatment responses were evaluated by computed tomography scans or positron emission tomography (PET) scan after at least 2-cycles of immunochemotherapy. Bone marrow aspiration and immunotyping were also routinely performed to determine bone marrow invasion at initial diagnosis. Therapeutic evaluation based on Lugano 2014 classification and divided into imaging remission and metabolic remission, including complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD) [19]. Adverse reactions assessment Routine physical examination, hematological and biochemistry tests, electrocardiogram and electrocardiograph, were done before and after every cycle of immunochemotherapy. Adverse effects were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [20]. Statistical analysis The laboratory and clinical date, response rates and adverse reactions between R-miniCHOP and BR groups were analyzed by using chi-square test and Mann Whitney U test. Statistical analyses were performed by using GraphPad 7.0 and the Statistical Package for the Social Sciences version 24.0. P -value < 0.05 was regarded as statistically significant. Results Baseline characteristics of patients Thirty-two patients were included from Union hospital of Wuhan and Xiangyang No.1 hospital between January 2020 and November 2020. The median age was 74 years (range 70 to 82), and the male to female ratio was 0.88:1. Twenty-five patients were diagnosed as DLBCL, seven patients with FL grade 3B. Eighteen patients (56.25%) were diagnosed at Stage IV. BR regimen was selected when patients presented with with medical comorbidities. Twenty patients were treated with R-miniCHOP, and twelve patients received BR instead. There were no significance in Age, Sex, Stage between two groups. The baseline characteristics are listed in Table 3 . Treatment and Response Two patients received 2 cycles of R-miniCHOP and one patient received 2 cycles of BR because of tumor progression and severe infection caused by myelosuppression. Three patients received 3-cycles of BR before this study was terminated. The rest of patients received 4-6 cycles of immunochemotherapy. The percentage CR rate was similar between both groups (35% vs 33.3%). The objective remission rate (ORR) in the BR group was minimally improved compared to the R-miniCHOP group (83.3% vs 75%), but with no statistical significance ( P = 0.581) as shown in Table. 4 . Adverse reactions Adverse events were classified as hematological and non-hematologic adverse reactions ( Table 5 ). The R-miniCHOP group had a higher incidence of leukopenia ( P = 0.029) compared to the BR group. Furthermore, six patients were reported to have an occurrence of infection, and four patients reported with cardiac events in the R-miniCHOP group. However, the BR group had a higher incidence of transient fever ( P = 0.036). Sensitivity analysis Univariate analyses were performed to clarify the relationship between prognostic factors and ORR of the 32 patients. In the univariate analysis, ECOG 0-1, no extranodal sites, LDH and ESR level, tumor mass <10 cm were unrelated with ORR. However, β2-microglobulin<3.0 mg/L maybe predictive of higher ORR ( P = 0.022) ( Table. S1 ). Discussion The Surveillance, Epidemiology and End Results (SEER) program predicted that the incidence of NHL would be estimated at around 4% of all cancer cases worldwide in 2024, with a median age at 66 years [21]. DLBCL accounts for about 31% of NHL cases, with the majority of DLBCL patients being over 60 years [6, 22]. Therefore, measures to improve patient outcomes, individual life expectancy, and survival for this category of patients must be enhanced. In the recent past, R-CHOP was the recommended standard regimen for the treatment DLBCL in older patients below the age of 80 years. Older patients aged 60-80 years with DLBCL could achieve a relatively high CR rate and prolonged median survival after 4-6 cycles of R-CHOP [3]. R-miniCHOP offered an improved comprise between safety and efficiency in patients aged 80 years and older as a substantial number of older people could be cured [4]. However, complications and adverse treatment reactions were reported to increase in patients aged 70 years and older [23]. Several risk factors, including comorbidity, functional impairment, cognitive decline, poor performance score and social isolation, contributed to the treatment-related toxicity [24]. Despite having R-CHOP or R-miniCHOP as treatment options in older patients, the presence of comorbidities and treatment-related toxicity, to some extent, contributes to limited available therapeutic options in real-world practice. Thus, promising regimens need to be exploited and in order to provide an optimal balance between efficiency and safety in older patients. Several studies demonstrated that the BR regimen was a promising prospect in both indolent and aggressive lymphomas because of its modest activity and manageable toxicity profile. The BRIGHT study reported that the BR regimen had a better long-term disease control than R-CHOP regimen and therefore, should be recommended as the first-line treatment in indolent and mantel-cell lymphoma [25]. Furthermore, a multicenter, retrospective study reported that the BR regimen was less toxic and more efficient compared to the R-CHOP regimen in patients with FL grade 3A [26]. BR regimen demonstrated a low rate of nonhematologic adverse events in older patients with chronic lymphocytic leukemia [27]. Moreover, BR regimen was well-tolerated and safety in indolent NHL patients with renal impairment [28]. In 2011, an exploratory clinical study suggested that BR may be an alternative treatment for aggressive lymphomas in older patients 80 years and older ineligible for R-CHOP therapy [29]. To date, a few studies have demonstrated BR was a feasible option for the first-line treatment of DLBCL in elderly patients [16, 30-32]. Table 6 illustrates the different ranges of ORR, CRR and median PFS in BR groups; ORR 50-83.3%, CRR 20-54% and median progression-free survival ranged 7.7-33 months. On the contrary, results obtained by the GELA analysis, ORR in the R-miniCHOP group was 75% [4]. BR showed nearly equivalent efficacy in this category of patients. Our study further verified the findings of the GELA analysis, the ORR was 83.3% and 75% in the BR group and R-miniCHOP group, respectively, with no statistical significance. Furthermore, in 32 patients, β2-microglobulin <3.0 mg/L was predictive of higher ORR in our univariate analyses of prognostic factors. In the previous study, nausea and vomiting were frequently reported in older patients after BR treatment. This adverse reaction was equally commonly reported in our study (50%) [26]. However, it was not of significance compared to R-miniCHOP group ( P =0.581). Importantly, the BR group had a lower rate of leukopenia compared to the R-miniCHOP group. This result showed that BR is likely to reduce the risk of infection and febrile neutropenia. Additionally, BR had a relative low rate of cardiac events due to the absence of anthracyclines, showing that BR is safer and tolerable for unfit older patients. It's worth noting that BR had a higher incidence of transient fever which could be attributed to drug-induced fever as the inflammatory indicators such as C-reaction protein and procalcitonin maintained within normal range. Generally, the body temperature could be quickly reduced to normal after auxiliary antipyretic treatment. However, when this symptom arises at the initiation of treatment, it is difficult for physicians to determine the cause of fever which may preclude treatment. The limitation of our study was that it was a small cohort size and short follow-up (eleven month) duration study. Bendamustine was brought to market in China on May 2019. So far, it was only used in part of first-ties cities. Furthermore, it is relatively expensive with the cost of bendamustine not being reimbursed by the national health insurance system in China. The number of elderly patients newly diagnosed with DLBCL and defined as unfit was small. Thus, it is a challenge to recruit enough unfit participants in such a short time. that was also the reason why overall survival and median progression-free survival were not analyzed in our study. For this reason, our study could not analyze overall survival and median progression-free survival. We believe that a large-scale and long-term follow-up prospective study will provide better insight into the future. The emergence of new targeted drugs also provides more options for the treatment of DLBCL. A recent clinical trial showed that the anti-CD79b antibody polatuzumab vedotin combined with BR could reduce the risk of death in relapsed/refractory DLBCL [33]. The novel histone deacetylases inhibitor chidamide could synergize with rituximab by upregulating CD20 expression in DLBCL and significantly inhibited the tumor growth in vitro and in vivo [34]. The phosphoinositide 3-kinase (PI3K) inhibitor copanlisib showed high cytotoxicity in vivo and could improve survival in DLBCL model [35]. Moreover, the Bcl-2 inhibitor venetoclax and Bruton's tyrosine kinase inhibitor ibrutinib could enhancing the sensitivity of PI3K inhibitor in actived B-cell like DLBCL [35, 36]. Thus, more clinical trials should be conducted to explore new therapeutic regimens for DLBCL. Conclusion Currently, the treatment for unfit older patients with DLBCL remains a daunting challenge for physicians. The choice of treatment should be individualized, with an accurate assessment of the risk-benefit ratio undertaken for each patient before treatment. As such, considering our results, BR is a promising regimen with lesser toxicity and higher efficacy for older patients with DLBCL. Therefore, BR is recommended as an alternative regimen of R-miniCHOP and a first-line regimen in unfit patients with DLBCL. Declarations Funding This study was supported by grant from the National Natural Science Foundation of China (No. 81672940) and the Clinical Research Physician Program of Tongji Medical College, Huazhong University of Science and Technology (No.5001530053). Authors’ contributions YHD and LLZ provided the direction of study. DDZ collected and analyzed the data, wrote the manuscript, NMK revised the manuscript. All authors read and approved the final manuscript. Conflict of interests The authors declare that they have no competing interests. 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Inhibition of SYK or BTK augments venetoclax sensitivity in SHP1-negative/BCL-2-positive diffuse large B-cell lymphoma. Leukemia. 2019; 33: 2416-28. Tables Table 1. Definition of unfit according to CGA Unfit Age ADL score IADL score CIRS-G >79 6 8 no grade-3/4 comorbidities and < 5 grade-2 comorbidities <80 5 6-7 no grade-3/4 comorbidities and 5-8 grade-2 comorbidities Note: ADL, activity of daily living; IADL, instrumental activity of daily living; CIRS-, Cumulative Illness Rating Score for Geriatrics; CGA, comprehensive geriatric assessment. Table 2. The R-miniCHOP and BR rigimens Agents Does Route Time R-miniCHOP Rituximab 375 mg/m 2 IV Day 1 Cyclophosphamide 375-562.5 mg/m 2 IV Day 2 Vincristine Vindesine 1.4 mg/ m 2 （D max ≤2 mg） 2-3 mg/m 2 (D max ≤3 mg) IV Day 2 Doxorubicin (liposome adriamycin) 25-35 mg/m 2 (10-15 mg/m 2 ) IV Day 2 Prednisone 100 mg PO Day 1-5 BR Rituximab 375 mg/m 2 IV Day 1 Bendamustine 60-90 mg/m 2 IV Day 2-3 Note: Both R-miniCHOP and BR regimen were repeated every 21 days. When elderly patients appeared with cardiac insufficiency, doxorubicin were often replaced with liposome adriamycin. IV, intravenously; PO, per os. Table 3. Characteristics of patients enrolled in the study Variables Number of patients (n=32) P R-miniCHOP (n=20) BR (n=12) Age 0.273 Range 70-81 70-82 Median 73 76 ≥70, 80 1 2 Sex 0.647 Male 10 5 Female 10 7 Pathology 0.740 FL, grade 3B 4 3 DLBCL 16 9 Stage (Lugano) 0.991 Ⅰ 3 2 Ⅱ 5 3 Ⅲ 2 1 Ⅳ 12 6 IPI 0.241 1 2 4 2 6 2 3 or more 12 6 ECOG 0.043 0 2 1 1 7 4 2 11 7 Note: P , Chi-square. Abbreviations: IPI, International Prognostic Index; ECOG: Eastern Cooperative Oncology Group Performance Status. Table 4. Overall response rates of R-miniCHOP and BR regimens Response R-miniCHOP (n=20) BR (n=12) P value Complete remission rate 35% (7/20) 33.3% (4/12) 0.923 Partial remission rate 40% (8/20) 50% (6/12) 0.580 Stable disease rate 10% (2/20) 8.3% (1/12) 0.875 Progressive disease rate 15% (3/20) 8.3% (1/12) 0.581 Objective remission rate 75% (15/20) 83.3% (10/12) 0.581 Table 5. Hematological and extra-hematological adverse events between R-miniCHOP and BR groups. Toxicity Grade of adverse reaction P value R-miniCHOP (n=20) BR (n=12) Hematologic Leukopenia 12 (60%) 3 (25%) 0.029 * Anemia 13 (65%) 6 (50%) 0.403 Thrombocytopenia 6 (30%) 2 (17%) 0.399 Non-hematologic Nausea and vomiting 8 (40%) 6 (50%) 0.581 ALT/AST elevation 6 (30%) 2 (17%) 0.399 Hypoalbuminemia 3 (15%) 2 (17%) 0.900 Cardiac disorders 4 (20%) 1 (8%) 0.378 Nervous system disorders 3 (15%) 1 (8%) 0.580 Allergy 5 (25%) 2 (17%) 0.581 Transient fever 2 (10%) 5 (42%) 0.036* Electrolyte imbalance 8 (40%) 7 (58%) 0.314 Infection 6 (30%) 1 (8%) 0.151 Table 6. Summary of prospective studies of BR as frontline treatment in elderly patients with newly diagnosed with DLBCL. Author and Year Region Patients Age Bendamustine ORR% CRR% mPFS Weidmann et al , 2011 Germany 13 85(80-95) 120 mg/m 2 /q3w 69% 54% 7.7 Horn et al , 2012 Germany 20 72 (51-86) 90 mg/m 2 /q4w 55% 20% 19.4 Park et al , 2016 USA 23 80 (>65) 120 mg/m 2 /q3w 78% 52% 10.2 Storti et al , 2018 Italy 49 81 (>70) 90 mg/m 2 /q4w 62% 53% 33 Cheng et al , 2018 Taiwan 26 81(75-93) 90 mg/m 2 /q3w 50% 42.3% 11.2 Current report, 2020 China 12 70 (70-82) 60-90 mg/m 2 /q3w 85.3% 33.3% NA Note: CRR: complete remission rate; ORR: overall response rate; mPFS: median progression-free survival; NA, not available Supplementary Files TableS1.docx Cite Share Download PDF Status: Posted Version 1 posted 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies 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-580186","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":35687523,"identity":"9cded6c7-0a00-4c79-9f3e-1109fc1f1753","order_by":0,"name":"Dongdong Zhang","email":"","orcid":"https://orcid.org/0000-0001-7611-3114","institution":"Hubei University of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dongdong","middleName":"","lastName":"Zhang","suffix":""},{"id":35687524,"identity":"a72c14f9-ce01-448a-87a9-95b9606f45d7","order_by":1,"name":"Tao Liu","email":"","orcid":"","institution":"Huazhong University of Science and Technology Tongji Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Liu","suffix":""},{"id":35687525,"identity":"a3019c38-2d6d-48d9-abaf-cd0377e33ce9","order_by":2,"name":"Natasha Kaweme","email":"","orcid":"","institution":"Wuhan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Natasha","middleName":"","lastName":"Kaweme","suffix":""},{"id":35687526,"identity":"1645e347-727c-4503-98a8-5b0eae49b770","order_by":3,"name":"Youhong Dong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/klEQVRIiWNgGAWjYDCCAxAqAYgZHyQY/JNjY28/QLQWZoMPFQeM+XjOJBCthU1yxpkDifMkHAzw6uA73nv4NU/F4Tx+6fYL0rxtd9LbJID6f1Rsw6lF8sy5NGueM4eLJeecKTDmbXuW2ybdeICx58xtnFoMbuSYAVUeTtxwIychmbeNObdN5kACM2MbkVoOA7Wks0kkGBDSYvwYoiX9YOOMM4cTCGqRPHPGjHHOmfTEmTNymBk+VKQZtgED+SA+v/Ad7zH+8KbCOrFfIv35jwQDG3n59vaDD35U4NYCBGxSPGCaBxEdB/CpBwLmjz/ANPsDAgpHwSgYBaNgpAIAobxk0sX/BKwAAAAASUVORK5CYII=","orcid":"","institution":"xiangyangshi diyi renmin yiyuan: Xiangyang No 1 People's Hospital Affiliated to Hubei University of Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Youhong","middleName":"","lastName":"Dong","suffix":""},{"id":35687527,"identity":"0adbda8b-cbc5-4c62-9728-4e992f47c8bb","order_by":4,"name":"Liling Zhang","email":"","orcid":"","institution":"Huazhong University of Science and Technology Tongji Medical College","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Liling","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2021-06-01 14:43:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-580186/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-580186/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":13701623,"identity":"42b07812-7f6e-411c-845d-1778fd12b90f","added_by":"auto","created_at":"2021-09-17 13:30:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":371903,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-580186/v1/b629e74e-2f40-4474-9867-24415c0e730c.pdf"},{"id":10882110,"identity":"84842e2f-9551-4fa4-abf3-6469e71d53f2","added_by":"auto","created_at":"2021-06-28 19:59:42","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":14355,"visible":true,"origin":"","legend":"","description":"","filename":"TableS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-580186/v1/146c4f39f6183f1bee1592a0.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003eBendamustine Plus Rituximab Versus R-Minichop as First-Line Treatment in Unfit Patients with Diffuse Large B-Cell Lymphoma\u003c/p\u003e","fulltext":[{"header":"Introduction","content":" \u003cp\u003eDiffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, with 40% incidence in patients age over 70 years old [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The chimeric anti-CD20 monoclonal antibody rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy (R-CHOP) has dramatically improved the overall survival in patients with DLBCL in the last two decades. R-CHOP was recommended as a standard treatment for patients with DLBCL by the Groupe d\u0026rsquo;Etudes des Lymphomes de l\u0026rsquo;Adulte (GELA), depending on patients\u0026rsquo; age. Full dose R-CHOP was initially preferred in adult patients and elderly patients aged 60\u0026ndash;80 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. An attenuated immunochemotherapy regimen, R-miniCHOP, was identified and showed favorable efficacy and safety in patients over 80 years old [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, the presence of comorbidities and concomitant infections often led to reduced tolerability to treatment-related toxicities, resulting in treatment discontinuation and treatment failure in older patients [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn lymphoma, the cut-off age 65 was defined as a watershed between younger and older patients [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The R-miniCHOP regimen recommended by GELA for the treatment of DLBCL is also based on whether the patients is 80 years or older. Nevertheless, treatment should be individualized while incorporating individual life expectancy, functional reserve and social support into consideration [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. A complete comprehensive geriatric assessment (CGA) should be undertaken to determine if older patients can tolerate intensive therapy with curative intent. CGA divides older patients into three categories: fit, unfit and frail, according to age, comorbidities and functional abilities of daily living [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. CGA has proved to be an efficacy tool to identify fit patients who can benefit from intensive curative approach [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. To date, there are few studies on therapeutic regimens applied in unfit patients except R-miniCHOP. Previously, studies had shown that treatment failure of R-miniCHOP in older patients (\u0026gt;\u0026thinsp;80) with DLBCL was associated with treatment-related toxicities and pre-existing medical comorbidities other than advanced age and relatively-low dose intensity [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Thus, more efficacious and low-toxicity regimens need to be exploited.\u003c/p\u003e \u003cp\u003eBendamustine is a unique bifunctional alkylating agent with antimetabolic properties and antitumor effects [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The rebirth of bendamustine was in that it exhibited synergistic antitumor effects combined with rituximab (BR) for the treatment of lymphoid malignancies [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Previous clinical trials reported that BR improved survival outcome in indolent non-Hodgkin lymphoma (NHL) and relapsed/refractory DLBCL patients [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. There are currently limited clinical data available to rationalize therapeutic regimens for unfit patients with newly diagnosed DLBCL. A prospective phase II study showed anti-CD20 monoclonal antibody obinutuzumab plus CHOP was efficacious and safe for treating unfit patients with DLBCL [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Recently, a phase II clinical trial demonstrated that the BR regimen was a promising first-line treatment for frail patients with DLBCL due to its promising activity and manageable toxicity profile [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere is no prospective study comparing BR and R-miniCHOP as frontline treatment in unfit patients at present. Our study investigated the efficacy, safety, toxicity profile, and overall remission rate (ORR) of BR compared to R-miniCHOP as first-line treatment in unfit patients with newly diagnosed DLBCL or follicular lymphoma (FL) grade 3B in China.\u003c/p\u003e "},{"header":"Materials And Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design and patient eligibility\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFL grade 3B is closely related to DLBCL and may transform to DLBCL. Therefore, the standard treatment regimens used in FL grade 3B are similar to that of DLBCL in routine clinical practice\u0026nbsp;[17]. In this study, patients newly diagnosed with DLBCL or FL grade 3B were enrolled from January 2020 to December 2020. Diagnosis of DLBCL or FL grade 3B based on histopathologic morphology, immunohistology and clinical feature recommended by WHO 2016\u0026nbsp;[18].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Patients were classified as unfit according to simple CGA. \u003cstrong\u003eTable 1\u003c/strong\u003e illustrates the inclusion criteria for this study\u0026nbsp;[9]. Patients considered to be unfit included in this study met the following criteria: (a) Age\u0026ge;70; (b) White blood cells\u0026ge;3.0\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u0026nbsp;or granulocytes\u0026nbsp;\u0026ge;1.5\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L, hemoglobin\u0026ge;90.0\u0026times;10\u003csup\u003e12\u003c/sup\u003e/L, platelets\u0026ge;100\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L; (c) Normal sinus rhythm, ejection fraction 50-70% on echocardiography; (d) ALT and AST levels below the 2\u0026times;upper limit of normal, serum albumin\u0026ge;30.0 g/L, serum creatinine below the 1.5\u0026times;upper limit of normal; (e) HIV/AIDS negative.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eClinical staging was based on\u0026nbsp;modified Lugano 2014 staging criteria. The risk stratification was identified using International Prognostic Index (IPI). All the patients were received at least 2 cycles of R-miniCHOP or BR, depending on patients\u0026rsquo; performance status and the presence of comorbidities. Clinical features of R-miniCHOP and BR regimens are summarized in \u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eIn patients presenting with potential worsening cardiac function, doxorubicin was replaced by the liposome Adriamycin.\u003c/p\u003e\n\u003cp\u003eThis study\u0026nbsp;was approved by the Ethics and Scientific Committee of\u0026nbsp;Union Hospital of Tongji Medical College, Huazhong University of Science and Technology with approval number\u0026nbsp;2020211. All the patients were given written informed consent before immunochemotherapy and the data were collected from electronic medical record of Union hospital, Tongji Medical college.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResponse evaluation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTreatment responses were evaluated by computed tomography scans or positron emission tomography (PET) scan after at least 2-cycles of immunochemotherapy. Bone marrow aspiration and immunotyping were also routinely performed to determine bone marrow invasion at initial diagnosis. Therapeutic evaluation based on Lugano 2014 classification and divided into imaging remission and metabolic remission, including complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD)\u0026nbsp;[19]. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdverse reactions assessment \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRoutine physical examination, hematological and biochemistry tests, electrocardiogram and\u0026nbsp;electrocardiograph, were done before and after every cycle of immunochemotherapy. Adverse effects were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0\u0026nbsp;[20].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe laboratory and clinical date, response rates and adverse reactions between R-miniCHOP and BR groups were analyzed by using chi-square test and Mann Whitney U test. Statistical analyses were performed by using GraphPad 7.0 and the Statistical Package for the Social Sciences version 24.0. \u003cem\u003eP\u003c/em\u003e-value \u0026lt; 0.05 was regarded as statistically significant.\u003c/p\u003e"},{"header":"Results","content":" \u003cp\u003e\u003cstrong\u003eBaseline characteristics of patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThirty-two patients were included from Union hospital of Wuhan and Xiangyang No.1 hospital between January 2020 and November 2020. The median age was 74 years (range 70 to 82), and the male to female ratio was 0.88:1. Twenty-five patients were diagnosed as DLBCL, seven patients with FL grade 3B. Eighteen patients (56.25%) were diagnosed at Stage IV. BR regimen was selected when patients presented with with medical comorbidities. Twenty patients were treated with R-miniCHOP, and twelve patients received BR instead. There were no significance in Age, Sex, Stage between two groups. The baseline characteristics are listed in \u003cstrong\u003eTable 3\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTreatment and Response\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo patients received 2 cycles of R-miniCHOP and one patient received 2 cycles of BR because of tumor progression and severe infection caused by myelosuppression. Three patients received 3-cycles of BR before this study was terminated. The rest of patients received 4-6 cycles of immunochemotherapy. The percentage CR rate was similar between both groups (35% vs 33.3%). The objective remission rate (ORR) in the BR group was minimally improved compared to the R-miniCHOP group (83.3% vs 75%), but with no statistical significance (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.581) as shown in \u003cstrong\u003eTable. 4\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdverse reactions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAdverse events were classified as hematological and non-hematologic adverse reactions (\u003cstrong\u003eTable 5\u003c/strong\u003e). The R-miniCHOP group had a higher incidence of leukopenia (\u003cem\u003eP\u003c/em\u003e = 0.029) compared to the BR group. Furthermore, six patients were reported to have an occurrence of infection, and four patients reported with\u0026nbsp;cardiac events in the R-miniCHOP group. However, the BR group had a higher incidence of transient fever\u0026nbsp;(\u003cem\u003eP\u003c/em\u003e = 0.036).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSensitivity analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUnivariate analyses were performed to clarify the relationship between prognostic factors and ORR of the 32 patients. In the univariate analysis,\u0026nbsp;ECOG 0-1, no extranodal sites, LDH and ESR level, tumor mass \u0026lt;10 cm were unrelated with ORR. However, \u0026beta;2-microglobulin\u0026lt;3.0 mg/L maybe predictive of higher ORR (\u003cem\u003eP\u003c/em\u003e = 0.022) (\u003cstrong\u003eTable. S1\u003c/strong\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe Surveillance, Epidemiology and End Results (SEER) program predicted that the incidence of NHL would be estimated at around 4% of all cancer cases worldwide in 2024, with a median age at 66 years\u0026nbsp;[21]. DLBCL accounts for about 31% of NHL cases, with the majority of DLBCL patients being over 60 years\u0026nbsp;[6, 22]. Therefore, measures to improve patient outcomes, individual life expectancy, and survival for this category of patients must be enhanced.\u003c/p\u003e\n\u003cp\u003eIn the recent past, R-CHOP was the recommended standard regimen for the treatment DLBCL in older patients below the age of 80 years. Older patients aged 60-80 years with DLBCL could achieve a relatively high CR rate and prolonged median survival after 4-6 cycles of R-CHOP\u0026nbsp;[3]. R-miniCHOP offered an improved comprise between safety and efficiency in patients aged 80 years and older as a substantial number of older people could be cured\u0026nbsp;[4]. However, complications and adverse treatment reactions were reported to increase in patients aged 70 years and older\u0026nbsp;[23]. Several risk factors, including comorbidity, functional impairment, cognitive decline, poor performance score and social isolation, contributed to the treatment-related toxicity\u0026nbsp;[24]. Despite having R-CHOP or R-miniCHOP as treatment options in older patients, the presence of comorbidities and treatment-related toxicity, to some extent, contributes to limited available therapeutic options in real-world practice. Thus, promising regimens need to be exploited and in order to provide an optimal balance between efficiency and safety in older patients.\u003c/p\u003e\n\u003cp\u003eSeveral studies demonstrated that the BR regimen was a promising prospect in both indolent and aggressive lymphomas because of its modest activity and manageable toxicity profile. The BRIGHT study reported that the BR regimen had a better long-term disease control than R-CHOP regimen and therefore, should be recommended as the first-line treatment in indolent and mantel-cell lymphoma\u0026nbsp;[25]. Furthermore, a multicenter, retrospective study reported that the BR regimen was less toxic and more efficient compared to the R-CHOP regimen in patients with FL grade 3A\u0026nbsp;[26]. BR regimen demonstrated a low rate of nonhematologic adverse events in older patients with chronic lymphocytic leukemia\u0026nbsp;[27]. Moreover, BR regimen was well-tolerated and safety in indolent NHL patients with renal impairment\u0026nbsp;[28].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn 2011, an exploratory clinical study suggested that BR may be an alternative treatment for aggressive lymphomas in older patients 80 years and older ineligible for R-CHOP therapy\u0026nbsp;[29]. To date, a few studies have demonstrated BR was a feasible option for the first-line treatment of DLBCL in elderly patients\u0026nbsp;[16, 30-32]. \u003cstrong\u003eTable 6\u003c/strong\u003e illustrates the different ranges of ORR, CRR and median PFS in BR groups; ORR 50-83.3%, CRR 20-54% and median progression-free survival ranged 7.7-33 months. On the contrary, results obtained by the GELA analysis, ORR in the R-miniCHOP group was 75%\u0026nbsp;[4]. BR showed nearly equivalent efficacy in this category of patients. Our study further verified the findings of the GELA analysis, the ORR was 83.3% and 75% in the BR group and R-miniCHOP group, respectively, with no statistical significance. Furthermore, in 32 patients, \u0026beta;2-microglobulin \u0026lt;3.0 mg/L was predictive of higher ORR in our univariate analyses of prognostic factors.\u003c/p\u003e\n\u003cp\u003eIn the previous study, nausea and vomiting were frequently reported in older patients after BR treatment. This adverse reaction was equally commonly reported in our study (50%)\u0026nbsp;[26]. However, it was not of significance compared to R-miniCHOP group (\u003cem\u003eP\u003c/em\u003e =0.581). Importantly, the BR group had a lower rate of leukopenia compared to the R-miniCHOP group. This result showed that BR is likely to reduce the risk of infection and febrile neutropenia. Additionally, BR had a relative low rate of cardiac events due to the absence of anthracyclines, showing that BR is safer and tolerable for unfit older patients. It\u0026apos;s worth noting that BR had a higher incidence of transient fever which could be attributed to drug-induced fever as the inflammatory indicators such as C-reaction protein and procalcitonin maintained within normal range. Generally, the body temperature could be quickly reduced to normal after auxiliary antipyretic treatment. However, when this symptom arises at the initiation of treatment, it is difficult for physicians to determine the cause of fever which may preclude treatment.\u003c/p\u003e\n\u003cp\u003eThe limitation of our study was that it was a small cohort size and short follow-up (eleven month) duration study. Bendamustine was brought to market in China on May 2019. So far, it was only used in part of first-ties cities. Furthermore, it is relatively expensive with the cost of bendamustine not being reimbursed by the national health insurance system in China. The number of elderly patients newly diagnosed with DLBCL and defined as unfit was small. Thus, it is a challenge to recruit enough unfit participants in such a short time. that was also the reason why overall survival and median progression-free survival were not analyzed in our study. For this reason, our study could not analyze overall survival and median progression-free survival. We believe that a large-scale and long-term follow-up prospective study will provide better insight into the future.\u003c/p\u003e\n\u003cp\u003eThe emergence of new targeted drugs also provides more options for the treatment of DLBCL. A recent clinical trial showed that the anti-CD79b antibody polatuzumab vedotin combined with BR could reduce the risk of death in relapsed/refractory DLBCL\u0026nbsp;[33]. The novel histone deacetylases inhibitor chidamide could synergize with rituximab by upregulating CD20 expression in DLBCL and significantly inhibited the tumor growth \u003cem\u003ein vitro\u003c/em\u003e and \u003cem\u003ein vivo\u003c/em\u003e [34]. The phosphoinositide 3-kinase (PI3K) inhibitor copanlisib showed high cytotoxicity in vivo and could improve survival in DLBCL model [35]. Moreover, the Bcl-2 inhibitor venetoclax and Bruton\u0026apos;s tyrosine kinase inhibitor ibrutinib could enhancing the sensitivity of PI3K inhibitor in actived B-cell like DLBCL [35, 36]. Thus, more clinical trials should be conducted to explore new therapeutic regimens for DLBCL.\u003c/p\u003e"},{"header":"Conclusion","content":" \u003cp\u003eCurrently, the treatment for unfit older patients with DLBCL remains a daunting challenge for physicians. The choice of treatment should be individualized, with an accurate assessment of the risk-benefit ratio undertaken for each patient before treatment. As such, considering our results, BR is a promising regimen with lesser toxicity and higher efficacy for older patients with DLBCL. Therefore, BR is recommended as an alternative regimen of R-miniCHOP and a first-line regimen in unfit patients with DLBCL.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by grant from the National Natural Science Foundation of China (No. 81672940) and the Clinical Research Physician Program of Tongji Medical College, Huazhong University of Science and Technology (No.5001530053).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYHD and LLZ provided the direction of study. DDZ collected and analyzed the data, wrote the manuscript, NMK revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe clinical data supporting the conclusions of this manuscript will be made available by the authors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003ed\u0026apos;Amore F, Brincker H, Christensen BE, Thorling K, Pedersen M, Nielsen JL, et al. Non-Hodgkin\u0026apos;s lymphoma in the elderly. A study of 602 patients aged 70 or older from a Danish population-based registry. The Danish LYEO-Study Group. Annals of oncology : official journal of the European Society for Medical Oncology. 1992; 3: 379-86.\u003c/li\u003e\n \u003cli\u003eFeugier P, Van Hoof A, Sebban C, Solal-Celigny P, Bouabdallah R, Ferm\u0026eacute; C, et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d\u0026apos;Etude des Lymphomes de l\u0026apos;Adulte. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2005; 23: 4117-26.\u003c/li\u003e\n \u003cli\u003eCoiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, et al. Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d\u0026apos;Etudes des Lymphomes de l\u0026apos;Adulte. Blood. 2010; 116: 2040-5.\u003c/li\u003e\n \u003cli\u003ePeyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S, et al. Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. The Lancet Oncology. 2011; 12: 460-8.\u003c/li\u003e\n \u003cli\u003eKobayashi Y, Miura K, Hojo A, Hatta Y, Tanaka T, Kurita D, et al. Charlson Comorbidity Index is an independent prognostic factor among elderly patients with diffuse large B-cell lymphoma. Journal of cancer research and clinical oncology. 2011; 137: 1079-84.\u003c/li\u003e\n \u003cli\u003eFields PA, Linch DC. Treatment of the elderly patient with diffuse large B cell lymphoma. British journal of haematology. 2012; 157: 159-70.\u003c/li\u003e\n \u003cli\u003eBalducci L, Extermann M. Management of cancer in the older person: a practical approach. 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Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2009; 27: 1492-501.\u003c/li\u003e\n \u003cli\u003eRummel MJ, Niederle N, Maschmeyer G, Banat GA, von Gr\u0026uuml;nhagen U, Losem C, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet (London, England). 2013; 381: 1203-10.\u003c/li\u003e\n \u003cli\u003eFlinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, et al. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014; 123: 2944-52.\u003c/li\u003e\n \u003cli\u003eHong JY, Yoon DH, Suh C, Kim WS, Kim SJ, Jo JC, et al. Bendamustine plus rituximab for relapsed or refractory diffuse large B cell lymphoma: a multicenter retrospective analysis. Annals of hematology. 2018; 97: 1437-43.\u003c/li\u003e\n \u003cli\u003eOhmachi K, Niitsu N, Uchida T, Kim SJ, Ando K, Takahashi N, et al. Multicenter phase II study of bendamustine plus rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2013; 31: 2103-9.\u003c/li\u003e\n \u003cli\u003eMerli F, Cavallo F, Salvi F, Tucci A, Musuraca G, Nassi L, et al. Obinutuzumab and miniCHOP for unfit patients with diffuse large B-cell lymphoma. A phase II study by Fondazione Italiana Linfomi. Journal of geriatric oncology. 2020; 11: 37-40.\u003c/li\u003e\n \u003cli\u003eStorti S, Spina M, Pesce EA, Salvi F, Merli M, Ruffini A, et al. Rituximab plus bendamustine as front-line treatment in frail elderly (\u0026gt;70 years) patients with diffuse large B-cell non-Hodgkin lymphoma: a phase II multicenter study of the Fondazione Italiana Linfomi. Haematologica. 2018; 103: 1345-50.\u003c/li\u003e\n \u003cli\u003eHorn H, Kohler C, Witzig R, Kreuz M, Leich E, Klapper W, et al. Gene expression profiling reveals a close relationship between follicular lymphoma grade 3A and 3B, but distinct profiles of follicular lymphoma grade 1 and 2. Haematologica. 2018; 103: 1182-90.\u003c/li\u003e\n \u003cli\u003eCazzola M. Introduction to a review series: the 2016 revision of the WHO classification of tumors of hematopoietic and lymphoid tissues. Blood. 2016; 127: 2361-4.\u003c/li\u003e\n \u003cli\u003eCheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014; 32: 3059-68.\u003c/li\u003e\n \u003cli\u003eDueck AC, Mendoza TR, Mitchell SA, Reeve BB, Castro KM, Rogak LJ, et al. Validity and Reliability of the US National Cancer Institute\u0026apos;s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). JAMA oncology. 2015; 1: 1051-9.\u003c/li\u003e\n \u003cli\u003eDeSantis CE, Lin CC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics, 2014. CA: a cancer journal for clinicians. 2014; 64: 252-71.\u003c/li\u003e\n \u003cli\u003eMartelli M, Ferreri AJ, Agostinelli C, Di Rocco A, Pfreundschuh M, Pileri SA. Diffuse large B-cell lymphoma. Critical reviews in oncology/hematology. 2013; 87: 146-71.\u003c/li\u003e\n \u003cli\u003eAdvani RH, Chen H, Habermann TM, Morrison VA, Weller EA, Fisher RI, et al. Comparison of conventional prognostic indices in patients older than 60 years with diffuse large B-cell lymphoma treated with R-CHOP in the US Intergroup Study (ECOG 4494, CALGB 9793): consideration of age greater than 70 years in an elderly prognostic index (E-IPI). British journal of haematology. 2010; 151: 143-51.\u003c/li\u003e\n \u003cli\u003ePal SK, Katheria V, Hurria A. Evaluating the older patient with cancer: understanding frailty and the geriatric assessment. CA: a cancer journal for clinicians. 2010; 60: 120-32.\u003c/li\u003e\n \u003cli\u003eFlinn IW, van der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, et al. First-Line Treatment of Patients With Indolent Non-Hodgkin Lymphoma or Mantle-Cell Lymphoma With Bendamustine Plus Rituximab Versus R-CHOP or R-CVP: Results of the BRIGHT 5-Year Follow-Up Study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019; 37: 984-91.\u003c/li\u003e\n \u003cli\u003eMondello P, Steiner N, Willenbacher W, Cerchione C, Nappi D, Mauro E, et al. Bendamustine plus Rituximab Versus R-CHOP as First-Line Treatment for Patients with Follicular Lymphoma Grade 3A: Evidence from a Multicenter, Retrospective Study. The oncologist. 2018; 23: 454-60.\u003c/li\u003e\n \u003cli\u003eWoyach JA, Ruppert AS, Heerema NA, Zhao W, Booth AM, Ding W, et al. Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL. The New England journal of medicine. 2018; 379: 2517-28.\u003c/li\u003e\n \u003cli\u003eRibes D, Hachem HEL, Oberic L, Vergez F, Delas A, Belliere J, et al. Bendamustine plus rituximab for indolent B-cell lymphoma of renal significance. American journal of hematology. 2018; 93: 356-62.\u003c/li\u003e\n \u003cli\u003eWeidmann E, Neumann A, Fauth F, Atmaca A, Al-Batran SE, Pauligk C, et al. Phase II study of bendamustine in combination with rituximab as first-line treatment in patients 80 years or older with aggressive B-cell lymphomas. Annals of oncology : official journal of the European Society for Medical Oncology. 2011; 22: 1839-44.\u003c/li\u003e\n \u003cli\u003eHorn J, Kleber M, Hieke S, Schmitt-Gr\u0026auml;ff A, W\u0026auml;sch R, Engelhardt M. Treatment option of bendamustine in combination with rituximab in elderly and frail patients with aggressive B-non-Hodgkin lymphoma: rational, efficacy, and tolerance. Annals of hematology. 2012; 91: 1579-86.\u003c/li\u003e\n \u003cli\u003eCheng CL, Liu JH, Chou SC, Yao M, Tang JL, Tien HF. Retrospective analysis of frontline treatment efficacy in elderly patients with diffuse large B-cell lymphoma. European journal of haematology. 2018; 101: 28-37.\u003c/li\u003e\n \u003cli\u003ePark SI, Grover NS, Olajide O, Asch AS, Wall JG, Richards KL, et al. A phase II trial of bendamustine in combination with rituximab in older patients with previously untreated diffuse large B-cell lymphoma. British journal of haematology. 2016; 175: 281-9.\u003c/li\u003e\n \u003cli\u003eSehn LH, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, et al. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2020; 38: 155-65.\u003c/li\u003e\n \u003cli\u003eGuan XW, Wang HQ, Ban WW, Chang Z, Chen HZ, Jia L, et al. Novel HDAC inhibitor Chidamide synergizes with Rituximab to inhibit diffuse large B-cell lymphoma tumour growth by upregulating CD20. Cell death \u0026amp; disease. 2020; 11: 20.\u003c/li\u003e\n \u003cli\u003eBojarczuk K, Wienand K, Ryan JA, Chen L, Villalobos-Ortiz M, Mandato E, et al. Targeted inhibition of PI3K\u0026alpha;/\u0026delta; is synergistic with BCL-2 blockade in genetically defined subtypes of DLBCL. Blood. 2019; 133: 70-80.\u003c/li\u003e\n \u003cli\u003eSasi BK, Martines C, Xerxa E, Porro F, Kalkan H, Fazio R, et al. Inhibition of SYK or BTK augments venetoclax sensitivity in SHP1-negative/BCL-2-positive diffuse large B-cell lymphoma. Leukemia. 2019; 33: 2416-28.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Definition of unfit according to CGA\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" width=\"19.971056439942114%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eUnfit\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"14.47178002894356%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.35311143270622%\"\u003e\n \u003cp\u003e\u003cstrong\u003eADL score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.050651230101302%\"\u003e\n \u003cp\u003e\u003cstrong\u003eIADL score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"34.153400868306804%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCIRS-G\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.083182640144667%\"\u003e\n \u003cp\u003e\u0026gt;79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.43399638336347%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.806509945750452%\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"42.67631103074141%\"\u003e\n \u003cp\u003eno grade-3/4 comorbidities\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eand \u0026lt; 5 grade-2 comorbidities\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"18.083182640144667%\"\u003e\n \u003cp\u003e\u0026lt;80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.43399638336347%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.806509945750452%\"\u003e\n \u003cp\u003e6-7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"42.67631103074141%\"\u003e\n \u003cp\u003eno grade-3/4 comorbidities\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eand 5-8 grade-2 comorbidities\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: ADL, activity of daily living; IADL, instrumental activity of daily living; CIRS-, Cumulative Illness Rating Score for Geriatrics; CGA, comprehensive geriatric assessment.\u003c/p\u003e\n\u003cp\u003eTable 2. The R-miniCHOP and BR rigimens\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.392739273927393%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAgents\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.042904290429043%\"\u003e\n \u003cp\u003e\u003cstrong\u003eDoes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.646864686468646%\"\u003e\n \u003cp\u003e\u003cstrong\u003eRoute\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.917491749174918%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" width=\"75.04132231404958%\"\u003e\n \u003cp\u003e\u003cstrong\u003eR-miniCHOP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.958677685950413%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.392739273927393%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.042904290429043%\"\u003e\n \u003cp\u003e375 mg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.646864686468646%\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.917491749174918%\"\u003e\n \u003cp\u003eDay 1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.392739273927393%\"\u003e\n \u003cp\u003eCyclophosphamide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.042904290429043%\"\u003e\n \u003cp\u003e375-562.5 mg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.646864686468646%\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.917491749174918%\"\u003e\n \u003cp\u003eDay 2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.392739273927393%\"\u003e\n \u003cp\u003eVincristine\u003c/p\u003e\n \u003cp\u003e\u003cem\u003eVindesine\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.042904290429043%\"\u003e\n \u003cp\u003e1.4 mg/ m\u003csup\u003e2\u003c/sup\u003e （D\u003csub\u003emax\u003c/sub\u003e\u0026le;2 mg）\u003c/p\u003e\n \u003cp\u003e2-3 mg/m\u003csup\u003e2\u0026nbsp;\u003c/sup\u003e(D\u003csub\u003emax\u003c/sub\u003e\u0026le;3 mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.646864686468646%\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.917491749174918%\"\u003e\n \u003cp\u003eDay 2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.392739273927393%\"\u003e\n \u003cp\u003eDoxorubicin\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(liposome adriamycin)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.042904290429043%\"\u003e\n \u003cp\u003e25-35 mg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(10-15 mg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.646864686468646%\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.917491749174918%\"\u003e\n \u003cp\u003eDay 2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.392739273927393%\"\u003e\n \u003cp\u003ePrednisone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.042904290429043%\"\u003e\n \u003cp\u003e100 mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.646864686468646%\"\u003e\n \u003cp\u003ePO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.917491749174918%\"\u003e\n \u003cp\u003eDay 1-5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.392739273927393%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.042904290429043%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.646864686468646%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.917491749174918%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.392739273927393%\"\u003e\n \u003cp\u003eRituximab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.042904290429043%\"\u003e\n \u003cp\u003e375 mg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.646864686468646%\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.917491749174918%\"\u003e\n \u003cp\u003eDay 1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.392739273927393%\"\u003e\n \u003cp\u003eBendamustine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.042904290429043%\"\u003e\n \u003cp\u003e60-90 mg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"18.646864686468646%\"\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.917491749174918%\"\u003e\n \u003cp\u003eDay 2-3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: Both R-miniCHOP and BR regimen were repeated every 21 days. When elderly patients appeared with cardiac insufficiency,\u0026nbsp;doxorubicin were often replaced with liposome adriamycin.\u0026nbsp;IV, intravenously; PO, per os.\u003c/p\u003e\n\u003cp\u003eTable 3. Characteristics of patients enrolled in the study\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"52.604166666666664%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of patients (n=32)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"49.834983498349835%\"\u003e\n \u003cp\u003e\u003cstrong\u003eR-miniCHOP\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=20) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"50.165016501650165%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBR\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=12)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e0.273\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e\u0026nbsp;Range\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e70-81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e70-82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003eMedian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e\u0026ge;70, \u0026lt;80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e\u0026gt;80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e0.647\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003ePathology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e0.740\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e\u0026nbsp;FL, grade 3B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e\u0026nbsp;DLBCL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003eStage (Lugano)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e0.991\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003eⅠ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003eⅡ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003eⅢ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003eⅣ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003eIPI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e0.241\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e3 or more\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003eECOG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e0.043\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.21527777777778%\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.38888888888889%\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"21.180555555555557%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: \u003cem\u003eP\u003c/em\u003e, Chi-square. Abbreviations: IPI, International Prognostic Index; ECOG: Eastern Cooperative Oncology Group Performance Status.\u003c/p\u003e\n\u003cp\u003eTable 4. Overall response rates of R-miniCHOP and BR regimens\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e\u003cstrong\u003eResponse\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e\u003cstrong\u003eR-miniCHOP (n=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBR (n=12)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.822429906542055%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP value\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.822429906542055%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003eComplete remission rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e35% (7/20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e33.3% (4/12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.822429906542055%\"\u003e\n \u003cp\u003e0.923\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003ePartial remission rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e40% (8/20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e50% (6/12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.822429906542055%\"\u003e\n \u003cp\u003e0.580\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003eStable disease rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e10% (2/20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e8.3% (1/12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.822429906542055%\"\u003e\n \u003cp\u003e0.875\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003eProgressive disease rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e15% (3/20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e8.3% (1/12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.822429906542055%\"\u003e\n \u003cp\u003e0.581\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003eObjective remission rate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e75% (15/20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.725856697819314%\"\u003e\n \u003cp\u003e83.3% (10/12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"16.822429906542055%\"\u003e\n \u003cp\u003e0.581\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 5. Hematological and extra-hematological adverse events between R-miniCHOP and BR groups.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003e\u003cstrong\u003eToxicity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"52.72459499263623%\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade of adverse reaction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"47.486033519553075%\"\u003e\n \u003cp\u003e\u003cstrong\u003eR-miniCHOP (n=20)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"52.513966480446925%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBR (n=12)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003e\u003cstrong\u003eHematologic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"52.72459499263623%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003eLeukopenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.03681885125184%\"\u003e\n \u003cp\u003e12 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.68777614138439%\"\u003e\n \u003cp\u003e3 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e0.029\u003cstrong\u003e*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003eAnemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.03681885125184%\"\u003e\n \u003cp\u003e13 (65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.68777614138439%\"\u003e\n \u003cp\u003e6 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e0.403\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003eThrombocytopenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.03681885125184%\"\u003e\n \u003cp\u003e6 (30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.68777614138439%\"\u003e\n \u003cp\u003e2 (17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e0.399\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-hematologic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"52.72459499263623%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003eNausea and vomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.03681885125184%\"\u003e\n \u003cp\u003e8 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.68777614138439%\"\u003e\n \u003cp\u003e6 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e0.581\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003eALT/AST elevation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.03681885125184%\"\u003e\n \u003cp\u003e6 (30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.68777614138439%\"\u003e\n \u003cp\u003e2 (17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e0.399\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003eHypoalbuminemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.03681885125184%\"\u003e\n \u003cp\u003e3 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.68777614138439%\"\u003e\n \u003cp\u003e2 (17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e0.900\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003eCardiac disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.03681885125184%\"\u003e\n \u003cp\u003e4 (20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.68777614138439%\"\u003e\n \u003cp\u003e1 (8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e0.378\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003eNervous system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.03681885125184%\"\u003e\n \u003cp\u003e3 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.68777614138439%\"\u003e\n \u003cp\u003e1 (8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e0.580\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003eAllergy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.03681885125184%\"\u003e\n \u003cp\u003e5 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.68777614138439%\"\u003e\n \u003cp\u003e2 (17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e0.581\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003eTransient fever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.03681885125184%\"\u003e\n \u003cp\u003e2 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.68777614138439%\"\u003e\n \u003cp\u003e5 (42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e0.036*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003eElectrolyte imbalance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.03681885125184%\"\u003e\n \u003cp\u003e8 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.68777614138439%\"\u003e\n \u003cp\u003e7 (58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e0.314\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"31.95876288659794%\"\u003e\n \u003cp\u003eInfection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"25.03681885125184%\"\u003e\n \u003cp\u003e6 (30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"27.68777614138439%\"\u003e\n \u003cp\u003e1 (8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"15.316642120765833%\"\u003e\n \u003cp\u003e0.151\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 6. Summary of prospective studies of BR as frontline treatment in elderly patients with newly diagnosed with DLBCL.\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.476510067114095%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAuthor and Year\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.201342281879194%\"\u003e\n \u003cp\u003e\u003cstrong\u003eRegion\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.201342281879194%\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.409395973154362%\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.71812080536913%\"\u003e\n \u003cp\u003e\u003cstrong\u003eBendamustine\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"8.993288590604028%\"\u003e\n \u003cp\u003e\u003cstrong\u003eORR%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.409395973154362%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCRR%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.590604026845638%\"\u003e\n \u003cp\u003e\u003cstrong\u003emPFS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.476510067114095%\"\u003e\n \u003cp\u003eWeidmann \u003cem\u003eet al\u003c/em\u003e, 2011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.201342281879194%\"\u003e\n \u003cp\u003eGermany\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.201342281879194%\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.409395973154362%\"\u003e\n \u003cp\u003e85(80-95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.71812080536913%\"\u003e\n \u003cp\u003e120 mg/m\u003csup\u003e2\u003c/sup\u003e/q3w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.651006711409396%\"\u003e\n \u003cp\u003e69%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"12.751677852348994%\"\u003e\n \u003cp\u003e54%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.590604026845638%\"\u003e\n \u003cp\u003e7.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.476510067114095%\"\u003e\n \u003cp\u003eHorn \u003cem\u003eet al\u003c/em\u003e, 2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.201342281879194%\"\u003e\n \u003cp\u003eGermany\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.201342281879194%\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.409395973154362%\"\u003e\n \u003cp\u003e72 (51-86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.71812080536913%\"\u003e\n \u003cp\u003e90 mg/m\u003csup\u003e2\u003c/sup\u003e/q4w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.651006711409396%\"\u003e\n \u003cp\u003e55%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"12.751677852348994%\"\u003e\n \u003cp\u003e20%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.590604026845638%\"\u003e\n \u003cp\u003e19.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.476510067114095%\"\u003e\n \u003cp\u003ePark \u003cem\u003eet al\u003c/em\u003e, 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.201342281879194%\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.201342281879194%\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.409395973154362%\"\u003e\n \u003cp\u003e80 (\u0026gt;65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.71812080536913%\"\u003e\n \u003cp\u003e120 mg/m\u003csup\u003e2\u003c/sup\u003e/q3w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.651006711409396%\"\u003e\n \u003cp\u003e78%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"12.751677852348994%\"\u003e\n \u003cp\u003e52%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.590604026845638%\"\u003e\n \u003cp\u003e10.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.476510067114095%\"\u003e\n \u003cp\u003eStorti \u003cem\u003eet al\u003c/em\u003e, 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.201342281879194%\"\u003e\n \u003cp\u003eItaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.201342281879194%\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.409395973154362%\"\u003e\n \u003cp\u003e81 (\u0026gt;70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.71812080536913%\"\u003e\n \u003cp\u003e90 mg/m\u003csup\u003e2\u003c/sup\u003e/q4w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.651006711409396%\"\u003e\n \u003cp\u003e62%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"12.751677852348994%\"\u003e\n \u003cp\u003e53%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.590604026845638%\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.476510067114095%\"\u003e\n \u003cp\u003eCheng \u003cem\u003eet al\u003c/em\u003e, 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.201342281879194%\"\u003e\n \u003cp\u003eTaiwan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.201342281879194%\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.409395973154362%\"\u003e\n \u003cp\u003e81(75-93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.71812080536913%\"\u003e\n \u003cp\u003e90 mg/m\u003csup\u003e2\u003c/sup\u003e/q3w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.651006711409396%\"\u003e\n \u003cp\u003e50%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"12.751677852348994%\"\u003e\n \u003cp\u003e42.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.590604026845638%\"\u003e\n \u003cp\u003e11.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"21.476510067114095%\"\u003e\n \u003cp\u003eCurrent report, 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.201342281879194%\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.201342281879194%\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.409395973154362%\"\u003e\n \u003cp\u003e70 (70-82)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"17.71812080536913%\"\u003e\n \u003cp\u003e60-90 mg/m\u003csup\u003e2\u003c/sup\u003e/q3w\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"7.651006711409396%\"\u003e\n \u003cp\u003e85.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" width=\"12.751677852348994%\"\u003e\n \u003cp\u003e33.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.590604026845638%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: CRR: complete remission rate; ORR: overall response rate; mPFS: median progression-free survival; NA, not available\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Diffuse large-B cell lymphoma, Bendamustine plus rituximab, R-miniCHOP, Unfit, Objective remission rate.","lastPublishedDoi":"10.21203/rs.3.rs-580186/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-580186/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: To evaluate the efficacy and safety of bendamustine plus rituximab (BR) and low-does CHOP chemotherapy regimen-rituximab combination (R-miniCHOP) in elderly patients with diffuse large-B cell lymphoma, unfit for full dose immunochemotherapy.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethod\u003c/strong\u003e: Patients over 70 years with diffuse larger B-cell lymphoma or follicular lymphoma grade 3B, defined as unfit according to Comprehensive Geriatric Assessment (CGA), were included in our study. BR or R-miniCHOP was individualized according to the patients’ performance status and the presence of comorbidities. All the patients were received 4-6 cycles of immunochemotherapy at three-week intervals. Objective remission rate and adverse reaction were evaluated between the two groups.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResult:\u003c/strong\u003e This study included thirty-two patients enrolled between January 2020 and November 2020. The median age was 74 years (range 70-82). Twelve patients received BR, whereas twenty patients were treated with R-miniCHOP. The objective remission rate in the BR group was a slightly higher than the R-miniCHOP group (83.3% vs 75%), but with no statistical significance (\u003cem\u003eP \u003c/em\u003e= 0.581). Furthermore, the objective remission rate was influenced by a serum beta 2 microglobulin concentration of 3 mg/L or less. The BR group showed a lower incidence of leukopenia than the R-miniCHOP group (\u003cem\u003eP \u003c/em\u003e= 0.029), but had a higher incidence of fever (\u003cem\u003eP \u003c/em\u003e= 0.036). \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eBR showed equivalent efficacy but more improved safety in unfit patients with diffuse large-B cell lymphoma compared to R-miniCHOP. BR should be considered as an alternative treatment in this subgroup of patients.\u003c/p\u003e","manuscriptTitle":"Bendamustine Plus Rituximab Versus R-Minichop as First-Line Treatment in Unfit Patients with Diffuse Large B-Cell Lymphoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-06-28 19:59:40","doi":"10.21203/rs.3.rs-580186/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2ea69e05-d018-4701-9f86-6dfacd0c7684","owner":[],"postedDate":"June 28th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":5322931,"name":"Oncology"}],"tags":[],"updatedAt":"2021-07-10T18:01:04+00:00","versionOfRecord":[],"versionCreatedAt":"2021-06-28 19:59:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-580186","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-580186","identity":"rs-580186","version":["v1"]},"buildId":"omnImTCwR2MFx8CMYfrG7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}