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.

Figure 1

Patient disposition. Enrollment: May 2011 to January 2013. (1) Forty-four patients enrolled and received single-agent carfilzomib 20/56 mg/m² with (2) 42 response evaluable and (3) 35 evaluable per protocol. (4) Patients who achieved less than PR within 2 cycles of single-agent carfilzomib could have (5) low-dose dexamethasone (20 mg) added to their regimen and continued treatment until POD or intolerable toxicity. (6) Patients who achieved at least PR within 2 cycles continued single-agent carfilzomib until POD, at which time they had the option of discontinuing treatment or (7) modifying the carfilzomib regimen with the addition of low-dose dexamethasone to potentially overcome resistance and prolong therapy. Data cutoff: June 2013. CFZ, carfilzomib; dex, dexamethasone; CFZ + dex, CFZ in combination with low-dose dex.

Figure 2

PFS and OS by the Kaplan-Meier method in response-evaluable patients (N = 42). NE, not estimable.