SAN FRANCISCO—Adding carfilzomib to lenalidomide and dexamethasone in patients with relapsed multiple myeloma is clinically meaningful in that it significantly improved progression-free survival (PFS) compared with lenalidomide and dexamethasone.
The interim results from the randomized, open-label phase 3 ASPIRE study (Abstract 79) were reported at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition.
The “unprecedented” median PFS of 26.3 months observed when carfilzomib was combined with the currently accepted “gold standard” regimen “could represent a new standard of care in multiple myeloma,” said A. Keith Stewart, MB, ChB, of the Division of Hematology-Oncology at the Mayo Clinic in Scottsdale, AZ.
The study randomly assigned 792 patients from 20 countries 1:1 to receive carfilzomib as a 10-minute infusion on days 1, 2, 8, 9, 15, and 16 during cycles 1-12 (20 mg/m2 [days 1 and 2 of cycle 1]; 27 mg/m2 thereafter) omitted on days 8 and 9 during cycles 13-18 and was not administered beyond 18 cycles, lenalidomide 25 mg on days 1-21, and dexamethasone 40 mg on days 1, 8, 15, and 22 of a 28-day cycle or to lenalidomide and dexamethasone.
At the time of the prespecified interim analysis, the study met the primary end point for PFS, which was a median of 26.3 months for the carfilzomib arm versus 17.6 months for the control group (hazard ratio [HR] 0.69; 95% confidence interval [CI] 0.57-0.83; P<0.0001).
The 24-month Kaplan-Meier overall survival (OS) rates were 73.3% for the carfilzomib arm and 65.0% for the control arm (HR for death, 0.79; 95% CI, 0.63-0.99; P=0.04).
Overall response rates were 87.1% in the carfilzomib arm and 66.7% in the control arm (P<0.0001), with 31.8% versus 9.3% achieving a complete response (CR) or better (14.1% versus 4.3% had a stringent CR) and 69.9% and 40.4% achieving at least a very good partial response (all P<0.0001). Median time to response was 1.6 months in the carfilzomib group and 2.3 months in the control arm.
Median OS was not reached in either group; however, there was a trend toward longer OS with carfilzomib versus the controls (HR 0.79; 95% CI 0.63-0.99; P=0.018), which did not meet the prespecified statistical boundary at the interim analysis of survival (P=0.005).
Over 18 cycles of treatment, carfilzomib consistently improved Global Health Status, with patients reporting superior health-related quality of life compared with lenalidomide/dexamethasone alone (P=0.0001).
The most common grade 3 or higher hematologic treatment-emergent AEs (TEAEs) were neutropenia (29.6% versus 26.5%), anemia (17.9% versus 17.2%), and thrombocytopenia (16.6% versus 12.3%), respectively. The most common grade 3 or higher nonhematologic TEAEs were hypokalemia (9.4% versus 4.9%), fatigue (7.7% versus 6.4%), and diarrhea (3.8% versus 4.1%).
Cardiac and renal events were reported at rates consistent with or lower than prior studies of single-agent carfilzomib.
Results of the pivotal trial were published in the New England Journal of Medicine online on December 6, 2014.