Bendamustine and rituximab (BR) versus dexamethasone, rituximab, and cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia

Jonas Paludo, Jithma P. Abeykoon, Amanda Shreders, Stephen M. Ansell, Shaji Kumar, Sikander Ailawadhi, Rebecca L. King, Amber B. Koehler, Craig B. Reeder, Francis K. Buadi, Angela Dispenzieri, Martha Q. Lacy, David Dingli, Thomas E. Witzig, Ronald S. Go, Wilson I. Gonsalves, Taxiarchis Kourelis, Rahma Warsame, Nelson Leung, Thomas M. Habermann, Suzanne Hayman, Yi Lin, Robert A. Kyle, S. Vincent Rajkumar, Morie A. Gertz, Prashant Kapoor

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.