Carfilzomib Gets Expanded FDA Approval for Multiple Myeloma

The US Food and Drug Administration (FDA) approved the proteasome inhibitor carfilzomib (Kyprolis) for the treatment of multiple myeloma, when used in combination with lenalidomide and dexamethasone. The regimen is approved in patients who have received one to three prior lines of therapy.

“The ability of this Kyprolis treatment regimen to produce deep and durable responses is critical toward extending the time patients live without their disease progressing,” said Keith Stewart, MB, ChB, of the Mayo Clinic in Scottsdale, Arizona, in a press release.

The new FDA approval was based on results of the ASPIRE trial, which were presented last December at the American Society of Hematology (ASH) Annual Meeting in San Francisco, and also published in the New England Journal of Medicine.

In that phase III trial, which included 792 patients, the difference in progression-free survival (PFS) was striking. The median PFS in the group who received carfilzomib along with lenalidomide and dexamethasone was 26.3 months, compared with 17.6 months in the control group, which received lenalidomide and dexamethasone alone. This yielded a hazard ratio (HR) of 0.69 (95% confidence interval [CI], 0.57–0.83; P = .0001).

The overall survival rates at 24 months were 73.3% with carfilzomib and 65% without, for an HR for death of 0.79 (95% CI, 0.63–0.99; P = .04). The overall response rate was also better with the study drug, at 87.1% vs 66.7% (P < .001). The study also found that carfilzomib patients reported superior health-related quality of life.

Carfilzomib is also approved as a single agent for treatment of multiple myeloma in patients who have received at least two prior therapies including bortezomib and an immunomodulatory agent, and who have progressed on or within 60 days of the last therapy.

The drug has also shown good results in the phase III ENDEAVOR trial; Amgen reported an interim analysis in March of this year. That study compared carfilzomib plus low-dose dexamethasone with bortezomib and low-dose dexamethasone in relapsed multiple myeloma. The trial had 929 patients, and at the interim analysis the median PFS with carfilzomib was 18.7 months vs 9.4 months with bortezomib.