Dexamethasone, rituximab and cyclophosphamide for relapsed and/or refractory and treatment-naïve patients with Waldenstrom macroglobulinemia.
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.
['Paludo|Jonas|J|0000-0002-7350-5531', 'Abeykoon|Jithma P|JP|', 'Kumar|Shaji|S|0000-0001-5392-9284', 'Shreders|Amanda|A|0000-0002-2602-1358', 'Ailawadhi|Sikander|S|', 'Gertz|Morie A|MA|', 'Kourelis|Taxiarchis|T|', 'King|Rebecca L|RL|', 'Reeder|Craig B|CB|', 'Leung|Nelson|N|', 'Kyle|Robert A|RA|', 'Buadi|Francis K|FK|', 'Habermann|Thomas M|TM|', 'Dingli|David|D|', 'Witzig|Thomas E|TE|', 'Dispenzieri|Angela|A|', 'Lacy|Martha Q|MQ|', 'Go|Ronald S|RS|', 'Lin|Yi|Y|', 'Gonsalves|Wilson I|WI|0000-0001-6890-969X', 'Warsame|Rahma|R|', 'Lust|John A|JA|', 'Rajkumar|S Vincent|SV|', 'Ansell|Stephen M|SM|', 'Kapoor|Prashant|P|']
D000328:Adult D000368:Aged D000369:Aged, 80 and over D000971:Antineoplastic Combined Chemotherapy Protocols D015415:Biomarkers D003520:Cyclophosphamide D003907:Dexamethasone D019468:Disease Management D019008:Drug Resistance, Neoplasm D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D009154:Mutation D053594:Myeloid Differentiation Factor 88 D012008:Recurrence D019233:Retreatment D000069283:Rituximab D016879:Salvage Therapy D016019:Survival Analysis D016896:Treatment Outcome D008258:Waldenstrom Macroglobulinemia
MYD88 IgM monoclonal gammopathy indolent lymphoma