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      Up-front rituximab maintenance improves outcome in patients with follicular lymphoma: a collaborative Nordic study

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          Abstract

          <p id="d10907359e285"> <div class="list"> <a class="named-anchor" id="d10907359e287"> <!-- named anchor --> </a> <ul class="so-custom-list"> <li id="d10907359e288"> <div class="so-custom-list-content so-ol"> <p class="first" id="d10907359e289">Patients who received R-chemo followed by MR had an improved 5-year PFS and OS independent of prognostic factors. </p> </div> </li> <li id="d10907359e291"> <div class="so-custom-list-content so-ol"> <p class="first" id="d10907359e292">A reduction of the risk of HT was observed among the MR patients of the training, but not of the validation, cohort. </p> </div> </li> </ul> </div> </p><p class="first" id="d10907359e296">The introduction of the anti-CD20 antibody rituximab in combination with chemotherapy (R-chemo) has improved the prognosis of patients with follicular lymphoma (FL). During the last decade, the addition of a maintenance treatment with rituximab (MR) after R-chemo has been tested with the hope of further improving the outcome of these patients. Using 2 independent population-based cohorts, we investigated the effect of up-front MR on time related end points as well as the risk of histological transformation (HT). FL patients were included if they: (1) completed first-line induction treatment with R-chemo, (2) were alive after induction treatment and eligible for MR, and (3) had no evidence of HT at this time point. The training cohort consisted of 733 Danish patients of whom 364 were consolidated with MR; 369 were not. Patients receiving MR more often had advanced clinical stage (90% vs 78%), high Follicular Lymphoma International Prognostic Index (FLIPI) score (64% vs 55%), and bone marrow infiltration (49% vs 40%). Those consolidated with MR had an improved 5-year overall survival (OS; 89% vs 81%; <i>P</i> = .001) and progression-free survival (PFS; 72% vs 60%; <i>P</i> &lt; .001). In the training cohort, MR was associated with a reduction of HT risk ( <i>P</i> = .049). Analyses of an independent validation cohort of 190 Finnish patients confirmed the favorable impact of MR on 5-year OS (89% vs 81%; <i>P</i> = .046) and PFS (70% vs 57%; <i>P</i> = .005) but did not find a reduced risk of HT. The present population-based data suggest that the outcome of patients with FL has improved after consolidation of R-chemo with MR. </p><p id="d10907359e317"> <div class="fig panel" id="absf1"> <a class="named-anchor" id="absf1"> <!-- named anchor --> </a> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/064aa3e6-39ce-49ae-a318-84eb8c7795bc/PubMedCentral/image/advances017673absf1"/> </div> <div class="panel-content"/> </div> </p>

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          Most cited references35

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          Obinutuzumab for the First-Line Treatment of Follicular Lymphoma

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            Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study.

            This randomized, noninferiority (NI), global, phase 3 study evaluated the efficacy and safety of bendamustine plus rituximab (BR) vs a standard rituximab-chemotherapy regimen (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP] or rituximab plus cyclophosphamide, vincristine, and prednisone [R-CVP]) for treatment-naive patients with indolent non-Hodgkin's lymphoma or mantle cell lymphoma. Investigators preassigned the standard treatment regimen they considered most appropriate for each patient; patients were randomized to receive BR (n = 224) or standard therapy (R-CHOP/R-CVP, n = 223) for 6 cycles; 2 additional cycles were permitted at investigator discretion. Response was assessed by a blinded independent review committee. BR was noninferior to R-CHOP/R-CVP, as assessed by the primary end point of complete response rate (31% vs 25%, respectively; P = .0225 for NI [0.88 margin]). The overall response rates for BR and R-CHOP/R-CVP were 97% and 91%, respectively (P = .0102). Incidences of vomiting and drug-hypersensitivity reactions were significantly higher in patients treated with BR (P < .05), and incidences of peripheral neuropathy/paresthesia and alopecia were significantly higher in patients treated with standard-therapy regimens (P < .05). These data indicate BR is noninferior to standard therapy with regard to clinical response with an acceptable safety profile. This trial was registered at www.clinicaltrials.gov as #NCT00877006.
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              The Danish Pathology Register.

              The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established. DPR contains patient, pathology, and workload data. All records are subject to error tracing. The DPR covers all pathology data in Denmark. The data is used by the pathologists in the daily diagnostic process. The National Board of Health uses the data in the Danish Cancer Registry and DPR is unique for research as data can be linked to tissue biobanks and clinical databases.
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                Author and article information

                Journal
                Blood Advances
                Blood Adv
                American Society of Hematology
                2473-9529
                2473-9537
                July 05 2018
                July 10 2018
                July 05 2018
                July 10 2018
                : 2
                : 13
                : 1562-1571
                Article
                10.1182/bloodadvances.2018017673
                6039650
                29976619
                f34c6ec2-a151-4c56-8770-71bc4e48d7e7
                © 2018
                History

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