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      Systematic review of therapy used in relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma


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          To identify real-world evidence on outcomes from therapies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), we systematically reviewed literature in Medline/Embase for DLBCL/FL-related articles on real-world results published during January 2012–May 2016. Among 33 included articles, therapies included stem cell transplant (SCT) and chemotherapy, including experimental regimens. The highest overall survival rates were observed for SCT, long considered an optimal strategy following initial relapse. Prognoses were inferior among DLBCL patients receiving rituximab-based regimens rather than SCT, particularly among studies that exclusively focused on those ineligible for SCT due to age or co-morbidity. A lack of viable treatment options for DLBCL/FL patients ineligible for SCT after relapse remains a significant gap in care.

          Lay abstract

          Non-Hodgkin lymphoma is the most prevalent blood cancer. Diffuse large B-cell lymphoma and follicular lymphoma account for nearly two-thirds of all non-Hodgkin lymphomas. One-third of patients with diffuse large B-cell lymphoma continue on to relapsed or refractory disease. While follicular lymphoma tends to be less aggressive, relapses do occur. Stem cell transplant and chemotherapy/immunotherapy are the current treatment options for relapsed or refractory patients. However, many patients are ineligible for stem cell transplant, due to age or preexisting medical conditions, so safe and effective treatment choices for these patients are a must. The lack of viable treatment options highlights this unmet need.

          Most cited references40

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          An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era.

          The International Prognostic Index (IPI) has been the basis for determining prognosis in patients with aggressive non-Hodgkin lymphoma (NHL) for the past 20 years. Using raw clinical data from the National Comprehensive Cancer Network (NCCN) database collected during the rituximab era, we built an enhanced IPI with the goal of improving risk stratification. Clinical features from 1650 adults with de novo diffuse large B-cell lymphoma (DLBCL) diagnosed from 2000-2010 at 7 NCCN cancer centers were assessed for their prognostic significance, with statistical efforts to further refine the categorization of age and normalized LDH. Five predictors (age, lactate dehydrogenase (LDH), sites of involvement, Ann Arbor stage, ECOG performance status) were identified and a maximum of 8 points assigned. Four risk groups were formed: low (0-1), low-intermediate (2-3), high-intermediate (4-5), and high (6-8). Compared with the IPI, the NCCN-IPI better discriminated low- and high-risk subgroups (5-year overall survival [OS]: 96% vs 33%) than the IPI (5 year OS: 90% vs 54%), respectively. When validated using an independent cohort from the British Columbia Cancer Agency (n = 1138), it also demonstrated enhanced discrimination for both low- and high-risk patients. The NCCN-IPI is easy to apply and more powerful than the IPI for predicting survival in the rituximab era.
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            Non-Hodgkin lymphoma.

            Lymphomas can affect any organ in the body, present with a wide range of symptoms, and be seen by primary care physicians and physicians from most specialties. They are traditionally divided into Hodgkin's lymphoma (which accounts for about 10% of all lymphomas) and non-Hodgkin lymphoma, which is the topic of this Seminar. Non-Hodgkin lymphoma represents a wide spectrum of illnesses that vary from the most indolent to the most aggressive malignancies. They arise from lymphocytes that are at various stages of development, and the characteristics of the specific lymphoma subtype reflect those of the cell from which they originated. Since this topic was last reviewed in The Lancet in 2012, advances in understanding the biology and genetics of non-Hodgkin lymphoma and the availability of new diagnostic methods and therapies have improved our ability to manage patients with this disorder.
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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.

                Author and article information

                Future Sci OA
                Future Sci OA
                Future Science OA
                Future Science Ltd (London, UK )
                July 2018
                19 July 2018
                : 4
                : 7
                : FSO322
                [1 ]Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, 40 Landsdowne Street, Cambridge, MA 02139, USA
                [2 ]Meta Research, Evidera, 500 Totten Pond Road, Fifth Floor, Waltham, MA 02451, USA
                [3 ]Data Analytics, Evidera, 7575 Trans-Canada Highway, Suite 404, St-Laurent, Quebec H4T 1V6, Canada
                [4 ]Meta Research, Evidera, Metro Building, 6 th Floor, 1 Butterwick, London W6 8DL, United Kingdom
                [5 ]Modelling and Simulation, Evidera, 7101 Wisconsin Avenue, Suite 1400, Bethesda, MD 20814, USA
                [6 ]Data Analytics, Evidera, 500 Totten Pond Road, Fifth Floor, Waltham, MA 02451, USA
                Author notes
                *Author for correspondence: Tel.: +1 617 444 4404; aaron.galaznik@ 123456takeda.com
                © 2018 Genomics Institute of the Novartis Research Foundation

                This work is licensed under a Creative Commons Attribution 4.0 License

                : 08 February 2018
                : 23 May 2018
                : 19 July 2018
                Systematic Review

                chemotherapy,dlbcl,fl,overall survival,refractory,relapse,response,rituximab,stem cell therapy,systematic literature review


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