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      Treatment Outcomes and Roles of Transplantation and Maintenance Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma: Results From Large Real-World Cohorts

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          PURPOSE

          Commonly used first-line (1L) treatments for mantle cell lymphoma include high-dose cytarabine-based induction followed by autologous stem-cell transplant (ASCT) for younger patients and several chemoimmunotherapy regimens for older patients. Continuous debates exist on the role of ASCT in younger patients and maintenance rituximab (MR) after bendamustine plus rituximab (BR).

          METHODS

          Retrospective data from 4,216 patients with mantle cell lymphoma in the Flatiron Health electronic record-derived deidentified database diagnosed between 2011 and 2021, mostly in US community oncology settings, were evaluated for treatment patterns and outcomes. The efficacy findings with ASCT and MR were validated in an independent cohort of 1,168 patients from 12 academic centers.

          RESULTS

          Among 3,614 patients with documented 1L treatment, BR was the most used. Among 1,265 patients age < 65 years, 30.5% received cytarabine-based induction and 23.5% received ASCT. There was no significant association between ASCT and real-world time to next treatment (hazard ratio [HR], 0.84; 95% CI, 0.68 to 1.03; P = .10) or overall survival (HR, 0.86; 95% CI, 0.63 to 1.18; P = .4) among ASCT-eligible patients. Among MR-eligible patients, MR after BR versus BR alone was associated with a longer real-world time to next treatment (HR, 1.96; 95% CI, 1.61 to 2.38; P < .001) and overall survival (HR, 1.51; 95% CI, 1.19 to 1.92; P < .001). The efficacy findings were consistent in the validation cohort.

          CONCLUSION

          In this large cohort of patients treated primarily in the US community setting, only one in four young patients received cytarabine or ASCT consolidation, suggesting the need to develop treatments that can be delivered effectively in routine clinical practice. Together with the validation cohort, data support future clinical trials exploring regimens without ASCT consolidation in young patients, whereas MR should be considered for patients after 1L BR and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

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          Most cited references33

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          A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma.

          There is no generally established prognostic index for patients with mantle cell lymphoma (MCL), because the International Prognostic Index (IPI) and Follicular Lymphoma International Prognostic Index (FLIPI) have been developed for diffuse large cell and follicular lymphoma patients, respectively. Using data of 455 advanced stage MCL patients treated within 3 clinical trials, we examined the prognostic relevance of IPI and FLIPI and derived a new prognostic index (MCL international prognostic index, MIPI) of overall survival (OS). Statistical methods included Kaplan-Meier estimates and the log-rank test for evaluating IPI and FLIPI and multiple Cox regression for developing the MIPI. IPI and FLIPI showed poor separation of survival curves. According to the MIPI, patients were classified into low risk (44% of patients, median OS not reached), intermediate risk (35%, 51 months), and high risk groups (21%, 29 months), based on the 4 independent prognostic factors: age, performance status, lactate dehydrogenase (LDH), and leukocyte count. Cell proliferation (Ki-67) was exploratively analyzed as an important biologic marker and showed strong additional prognostic relevance. The MIPI is the first prognostic index particularly suited for MCL patients and may serve as an important tool to facilitate risk-adapted treatment decisions in patients with advanced stage MCL.
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            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.

            Rituximab plus chemotherapy, most often CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), is the first-line standard of care for patients with advanced indolent lymphoma, and for elderly patients with mantle-cell lymphoma. Bendamustine plus rituximab is effective for relapsed or refractory disease. We compared bendamustine plus rituximab with CHOP plus rituximab (R-CHOP) as first-line treatment for patients with indolent and mantle-cell lymphomas. We did a prospective, multicentre, randomised, open-label, non-inferiority trial at 81 centres in Germany between Sept 1, 2003, and Aug 31, 2008. Patients aged 18 years or older with a WHO performance status of 2 or less were eligible if they had newly diagnosed stage III or IV indolent or mantle-cell lymphoma. Patients were stratified by histological lymphoma subtype, then randomly assigned according to a prespecified randomisation list to receive either intravenous bendamustine (90 mg/m(2) on days 1 and 2 of a 4-week cycle) or CHOP (cycles every 3 weeks of cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and vincristine 1.4 mg/m(2) on day 1, and prednisone 100 mg/day for 5 days) for a maximum of six cycles. Patients in both groups received rituximab 375 mg/m(2) on day 1 of each cycle. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival, with a non-inferiority margin of 10%. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00991211, and the Federal Institute for Drugs and Medical Devices of Germany, BfArM 4021335. 274 patients were assigned to bendamustine plus rituximab (261 assessed) and 275 to R-CHOP (253 assessed). At median follow-up of 45 months (IQR 25-57), median progression-free survival was significantly longer in the bendamustine plus rituximab group than in the R-CHOP group (69.5 months [26.1 to not yet reached] vs 31.2 months [15.2-65.7]; hazard ratio 0.58, 95% CI 0.44-0.74; p<0.0001). Bendamustine plus rituximab was better tolerated than R-CHOP, with lower rates of alopecia (0 patients vs 245 (100%) of 245 patients who recieved ≥3 cycles; p<0.0001), haematological toxicity (77 [30%] vs 173 [68%]; p<0.0001), infections (96 [37%] vs 127 [50%]); p=0.0025), peripheral neuropathy (18 [7%] vs 73 [29%]; p<0.0001), and stomatitis (16 [6%] vs 47 [19%]; p<0.0001). Erythematous skin reactions were more common in patients in the bendamustine plus rituximab group than in those in the R-CHOP group (42 [16%] vs 23 [9%]; p=0.024). In patients with previously untreated indolent lymphoma, bendamustine plus rituximab can be considered as a preferred first-line treatment approach to R-CHOP because of increased progression-free survival and fewer toxic effects. Roche Pharma AG, Ribosepharm/Mundipharma GmbH. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Rituximab after Autologous Stem-Cell Transplantation in Mantle-Cell Lymphoma.

              Mantle-cell lymphoma is generally incurable. Despite high rates of complete response after initial immunochemotherapy followed by autologous stem-cell transplantation, patients have relapses. We investigated whether rituximab maintenance therapy at a dose of 375 mg per square meter of body-surface area administered every 2 months for 3 years after transplantation would prolong the duration of response.
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                Author and article information

                Journal
                J Clin Oncol
                J Clin Oncol
                jco
                JCO
                Journal of Clinical Oncology
                Wolters Kluwer Health
                0732-183X
                1527-7755
                20 January 2023
                28 June 2022
                28 June 2022
                : 41
                : 3
                : 541-554
                Affiliations
                [ 1 ]Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY
                [ 2 ]Department of Hematology, Winship Cancer Institute, Emory University, Atlanta, GA
                [ 3 ]Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
                [ 4 ]Memorial Sloan Kettering Cancer Center, New York, NY
                [ 5 ]Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
                [ 6 ]BC Cancer Centre for Lymphoid Cancer and University of British Columbia, Vancouver, British Columbia, Canada
                [ 7 ]Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA
                [ 8 ]Division of Oncology, Department of Medicine, Washington University School of Medicine, St Louis, MO
                [ 9 ]Arthur G James Comprehensive Cancer Center, The Ohio State University, Columbus, OH
                [ 10 ]Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
                [ 11 ]Janssen Research and Development, Titusville, NJ
                [ 12 ]Janssen Research and Development, Oncology, Raritan, NJ
                Author notes
                Peter Martin, MD, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY 10065; e-mail: pem9019@ 123456med.cornell.edu .
                Author information
                https://orcid.org/0000-0001-7813-1551
                https://orcid.org/0000-0002-2723-6481
                https://orcid.org/0000-0001-9748-5486
                https://orcid.org/0000-0002-1381-5810
                https://orcid.org/0000-0002-4625-3009
                https://orcid.org/0000-0002-5563-9325
                https://orcid.org/0000-0003-0459-6609
                https://orcid.org/0000-0002-1346-3157
                https://orcid.org/0000-0002-8942-2888
                https://orcid.org/0000-0002-9541-8666
                Article
                JCO.21.02698 00016
                10.1200/JCO.21.02698
                9870229
                35763708
                5b59ef2f-5bdb-43fe-bfd3-bc080fdba62b
                © 2022 by American Society of Clinical Oncology

                Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/

                History
                : 18 November 2021
                : 27 April 2022
                : 19 May 2022
                Page count
                Figures: 6, Tables: 3, Equations: 0, References: 34, Pages: 0
                Categories
                ORIGINAL REPORTS
                Hematologic Malignancy
                Custom metadata
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