British Journal of Haematology
British Journal of Haematology
5 years ago

Dexamethasone, rituximab and cyclophosphamide for relapsed and/or refractory and treatment-naïve patients with Waldenstrom macroglobulinemia

Morie A. Gertz, John A. Lust, Angela Dispenzieri, Jonas Paludo, Rebecca L. King, Nelson Leung, Stephen M. Ansell, Robert A. Kyle, Martha Q. Lacy, Wilson I. Gonsalves, Yi Lin, Prashant Kapoor, S. Vincent Rajkumar, Amanda Shreders, Ronald S. Go, Thomas M. Habermann, Sikander Ailawadhi, Rahma Warsame, Craig B. Reeder, Taxiarchis Kourelis, Jithma P. Abeykoon, David Dingli, Francis K. Buadi, Thomas E. Witzig, Shaji Kumar
The management of Waldenström macroglobulinaemia (WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide (DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88WT genotype. Herein, we additionally report on the activity of DRC based on the MYD88L265P mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate (ORR) was 87%. The median progression-free survival (PFS) and time-to-next-therapy (TTNT) were 32 (95% confidence interval [CI]: 15–51) and 50 (95% CI: 35–60) months, respectively. In the previously untreated cohort (n = 50), the ORR was 96%, and the median PFS and TTNT were 34 months (95% CI: 23–not reached [NR]) and NR (95% CI: 37–NR), respectively. Twenty-five (86%) of 29 genotyped patients harbored MYD88L265P. The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Similar to the frontline setting, DRC is an effective and well-tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed-duration option, with preliminary data suggesting efficacy independent of the patients’ MYD88 status.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/bjh.14826

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