The U.S. Food and Drug Administration (FDA) approved carfilzomib (Kyprolis) in combination with lenalidomide (Revlimid) and dexamethasone for the treatment of patients with relapsed multiple myeloma who have received one to three prior lines of therapy.
In the United States, there are nearly 96,000 people living with, or in remission from, multiple myeloma. The estimated number of new cases of multiple myeloma in 2014 was more than 24,000, and the estimated number of deaths was 11,090.
The approval was based on a demonstration of improved progression-free survival in the multicenter, open-label ASPIRE trial. In this international, randomized phase III trial, 792 patients with relapsed or refractory multiple myeloma after one to three lines of prior therapies were randomly assigned (1:1) to receive lenalidomide and dexamethasone with or without carfilzomib for 18 cycles.
Lenalidomide and dexamethasone were continued thereafter until disease progression. There was no planned crossover from the control arm to treatment with carfilzomib.
The study demonstrated a statistically significant prolongation of progression-free survival, as determined by an independent review committee (hazard ratio [HR] = 0.69; 95% confidence interval [CI] = 0.57–0.83; P = .0001, stratified log-rank test).
Median progression-free survival was 26.3 months in patients receiving carfilzomib plus lenalidomide and dexamethasone and 17.6 months in those receiving lenalidomide and dexamethasone alone. A treatment effect was observed across all subgroups tested, but the magnitude of the treatment effect was reduced in patients with a higher tumor burden at study baseline.
An interim analysis of overall survival, the key secondary endpoint, was conducted at the same time and found that the difference in overall survival did not reach the prespecified boundary for statistical significance. A partial response or better was achieved by 87% of patients on the three-drug arm and 67% on the two-drug arm.
The safety profile of carfilzomib in the three-drug combination was similar to that described in the current label. Serious adverse events were reported in 60% of patients in the three-drug arm and 54% in the two-drug arm. Cardiovascular events, venous thromboembolic events, and thrombocytopenia occurred more frequently in patients on carfilzomib. ■