Carfilzomib, rituximab, and dexamethasone (CaRD) treatment offers a neuropathy-sparing approach for treating Waldenstr?m's macroglobulinemia

摘要

Bortezomib frequently produces severe treatment-related peripheral neuropathy (PN) in Waldenstr?m's macroglobulinemia (WM). Carfilzomib is a neuropathy-sparing proteasome inhibitor. We examined carfilzomib, rituximab, and dexamethasone (CaRD) in symptomatic WM patients na?ve to bortezomib and rituximab. Protocol therapy consisted of intravenous carfilzomib, 20mg/m 2(cycle 1) and 36 mg/m2 (cycles 2-6), with in travenous dexamethasone, 20 mg, on days 1, 2, 8, and 9, and rituximab, 375 mg/m 2, on days 2 and 9 every 21 days. Maintenance therapy followed 8 weeks later with intravenous carfilzomib, 36 mg/m2, and intravenous dexamethasone, 20 mg, on days 1 and 2, and rituximab, 375 mg/m2, on day 2 every 8 weeks for 8 cycles. Overall response rate was 87.1%(1 complete response, 10 very good partial responses, 10 partial responses, and 6 minimal responses) and was not impacted by MYD88L265P or CXCR4WHIM mutation status. With a median follow-up of 15.4 months, 20 patients remain progression free. Grade ≥2 toxicities included asymptomatic hyperlipasemia (41.9%), reversible neutropenia (12.9%), and cardiomyopathy in 1 patient (3.2%) with multiple risk factors, and PN in 1 patient (3.2%) which was grade 2. Declines in serum IgA and IgG were common. CaRD offers a neuropathy-sparing approach for proteasomeinhibitor-based therapy in WM. This trial is registered at www.clinicaltrials.gov as #NCT01470196.