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

Abstract

Bortezomib frequently produces severe treatment-related peripheral neuropathy (PN) in Waldenström's macroglobulinemia (WM). Carfilzomib is a neuropathy-sparing proteasome inhibitor. We examined carfilzomib, rituximab, and dexamethasone (CaRD) in symptomatic WM patients naïve to bortezomib and rituximab. Protocol therapy consisted of intravenous carfilzomib, 20 mg/m2 (cycle 1) and 36 mg/m(2) (cycles 2-6), with intravenous 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/m(2), and intravenous dexamethasone, 20 mg, on days 1 and 2, and rituximab, 375 mg/m(2), 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 MYD88(L265P) or CXCR4(WHIM) 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 proteasome inhibitor-based therapy in WM. This trial is registered at www.clinicaltrials.gov as #NCT01470196.

• Authors: Steven P Treon, Christina K Tripsas, Kirsten Meid, Sandra Kanan, Patricia Sheehy, Stacey Chuma, Lian Xu, Yang Cao, Guang Yang, Xia Liu, Christopher J Patterson, Diane Warren, Zachary R Hunter, Barry Turnbull, Irene M Ghobrial, Jorge J Castillo
• Journal: Blood (Blood) Vol. 124 Issue 4 Pg. 503-10 (Jul 24 2014) ISSN: 1528-0020 [Electronic] United States
• PMID: 24859363 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by The American Society of Hematology.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Immunoglobulin G
• Immunoglobulin M
• Oligopeptides
• Rituximab
• carfilzomib
• Dexamethasone

Topics

• Aged
• Antibodies, Monoclonal, Murine-Derived (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Dexamethasone (administration & dosage)
• Female
• Follow-Up Studies
• Humans
• Immunoglobulin G (metabolism)
• Immunoglobulin M (metabolism)
• Male
• Middle Aged
• Oligopeptides (administration & dosage)
• Peripheral Nervous System Diseases (metabolism, mortality, prevention & control)
• Prognosis
• Prospective Studies
• Remission Induction
• Rituximab
• Survival Rate
• Waldenstrom Macroglobulinemia (drug therapy, metabolism, mortality)