A phase 2 single-center study of carfilzomib 56 mg/m2 with or without low-dose dexamethasone in relapsed multiple myeloma.

Abstract

Standard carfilzomib (20 mg/m(2) cycle 1, 27 mg/m(2) thereafter; 2- to 10-minute infusion) is safe and effective in relapsed or refractory multiple myeloma (R/RMM). We report phase 2 results of carfilzomib 20 mg/m(2) on days 1 to 2 of cycle 1, 56 mg/m(2) thereafter (30-minute infusion), in R/RMM with the option of adding dexamethasone (20 mg) for suboptimal response/progression. Forty-four patients enrolled, all having prior bortezomib and immunomodulatory drugs and a median of 5 prior regimens. Of 42 response-evaluable patients, 23 (55%) achieved at least partial response (PR). Median (95% confidence interval) duration of response, progression-free, and overall survival were 11.7 (6.7-14.7), 4.1 (2.5-11.8), and 20.3 months (6.4-not estimable), respectively. High-risk cytogenetics did not impact outcomes. Treatment was active in bortezomib-refractory subgroups, but these patients tended to have poorer outcomes. Four/10 patients with prior allogeneic transplant achieved at least PR. Of 6 patients who responded, progressed and had dexamethasone added, 4 achieved at least stable disease. The most frequent grade 3/4 adverse events (AEs) possibly related to carfilzomib included lymphopenia (43%), thrombocytopenia (32%), hypertension (25%), pneumonia (18%), and heart failure (11%). Seven patients (16%) discontinued treatment due to AEs. Carfilzomib 56 mg/m(2) ± dexamethasone was tolerable and provided durable responses. This trial was registered at www.clinicaltrials.gov as #NCT01351623.

• Authors: Nikoletta Lendvai, Patrick Hilden, Sean Devlin, Heather Landau, Hani Hassoun, Alexander M Lesokhin, Ioanna Tsakos, Kaitlyn Redling, Guenther Koehne, David J Chung, Wendy L Schaffer, Sergio A Giralt
• Journal: Blood (Blood) Vol. 124 Issue 6 Pg. 899-906 (Aug 07 2014) ISSN: 1528-0020 [Electronic] United States
• PMID: 24963043 (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

• Boronic Acids
• Oligopeptides
• Pyrazines
• Thalidomide
• Bortezomib
• carfilzomib
• Dexamethasone
• Lenalidomide

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Boronic Acids (therapeutic use)
• Bortezomib
• Dexamethasone (administration & dosage)
• Disease Progression
• Disease-Free Survival
• Female
• Humans
• Kaplan-Meier Estimate
• Lenalidomide
• Male
• Middle Aged
• Multiple Myeloma (drug therapy, genetics)
• Oligopeptides (administration & dosage, adverse effects)
• Pyrazines (therapeutic use)
• Risk Factors
• Thalidomide (analogs & derivatives, therapeutic use)
• Treatment Outcome