Bendamustine and rituximab (BR) versus dexamethasone, rituximab, and cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia
The treatment approaches for Waldenstrom macroglobulinemia (WM) are largely based upon information from single-arm phase II trials, without comparative data. We compared the efficacy of two commonly used regimens in routine practice (bendamustine-rituximab (BR) and dexamethasone, rituximab plus cyclophosphamide (DRC)) and evaluated their activity with respect to the patients’ MYD88L265P mutation status. Of 160 consecutive patients, 60 received BR (43 with relapsed/refractory WM) and 100 received DRC (50 had relapsed/refractory WM). In the treatment-naïve setting, overall response rate (ORR) was 93% with BR versus 96% with DRC (p = 0.55). Two-year progression-free survival (PFS) with BR and DRC was 88 and 61%, respectively (p = 0.07). In salvage setting, ORR was 95% with BR versus 87% with DRC, p = 0.45; median PFS with BR was 58 versus 32 months with DRC (2-year PFS was 66 versus 53%; p = 0.08). Median disease-specific survival was not reached with BR versus 166 months with DRC (p = 0.51). The time-to-event endpoints and depth of response were independent of the MYD88 mutation status. Grade ≥ 3 adverse events of both regimens were comparable. A trend for longer PFS was observed with BR although the regimens have comparable toxicities. The activity of BR and DRC appears to be unaffected by patients’ MYD88 mutation status.
KeywordsMYD88 Drug therapy Lymphoma Immunoglobulin M Lymphoplasmacytic lymphoma
J.P., P.K., and S.M.A. designed the research. J.P., J.P.A., A.S., S.A., R.K., A.B.H., and P.K. collect and assembled the data. J.P, J.P.A, and P.K. analyzed the data. All authors interpreted the data. J.P., J.P.A., S.K., and P.K. wrote the draft of the paper and all authors contributed in writing and approved the final version of the manuscript.
Compliance with ethical standards
The study was approved by the institutional review board and conducted in accordance with the Declaration of Helsinki.
Informed consent prior to the data collection and analysis for research purposes was obtained from the subjects in the study.
Conflict of interest
Dr. Ansell has received research funding from Bristol-Myers Squibb, Celldex, Merck, Affimed, and Seattle Genetics. Dr. Kumar has received honoraria from Skyline Diagnostics. Research support from Abbvie, Celgene, Novartis, Amgen, Takeda, Sanofi, and Janssen has been provided to Institution for conduct of clinical trials on which Dr. Kumar serves as a principal investigator. Dr. Ailawadhi has served as a consultant for Novartis Pharmaceuticals, Amgen Pharmaceuticals, Pharmacyclics, Inc., and Takeda and has received research funding from Pharmacyclics, Inc. Dr. Reeder has received research support from Celgene, Novartis, and Millennium. No other disclosures are reported. Dr. Dispenzieri has received research support from Celgene, Takeda, Pfizer, Alnylam, Prothena, and Jannsen. Dr. Lacy receives research funding from Celgene. Dr. Dingli has received research funding from Takeda, Karyopharm, and Amgen. Dr. Witzig reports receiving research funding from Celgene (Institution), Novartis (Institution), Spectrum Pharmaceuticals (Institution), and Acerta Pharma (Institution). Dr. Lin receives research funding from Janssen. Dr. Gertz has received research support from Ionis Pharmaceuticals and Prothena and honoraria from Celgene, Millennium Pharmaceuticals, and Novartis. Dr. Kapoor has received research funding from Takeda (Institution), Onyx (Institution), and Celgene (Institution) and consulting fees from Celgene and Sanofi (Institution). The rest of the authors declare that they have no conflict of interest.
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