Kyprolis Label Gets Updated Improved Survival Data for Patients With Relapsed/Refractory MM

The FDA has approved a supplemental New Drug Application (NDA) to add new overall survival (OS) data for carfilzomib (Kyprolis). The label will now show that carfilzomib and dexamethasone reduced the risk of death by 21% and increased OS by 7.6 months compared with bortezomib (Velcade) and dexamethasone in patients with relapsed or refractory multiple myeloma (MM).

The submitted results were based on data from the phase 3 head-to-head ENDEAVOR trial. David M. Reese, MD, senior vice president of Translational Sciences and Oncology at Amgen, noted that the superior improvement in OS is important. Between 2003 and 2013, the blood cancer therapies that the FDA approved had only improved OS by an average of 2.61 months.

“Kyprolis and dexamethasone improved overall survival by 7.6 months, underscoring that this regimen is a significant advancement and should be considered a standard of care for patients with relapsed or refractory multiple myeloma,” he said in a statement.

The same day that Amgen’s new OS data was approved to be added to the label, the Journal of Clinical Oncology published data from the phase 3 ASPIRE trial that demonstrated positive OS findings. Patients with relapsed MM who had already tried 1 to 3 prior lines of therapy were randomly assigned to receive either carfilzomib, lenalidomide, and dexamethasone or lenalidomide and dexamethasone.

Adding carfilzomib to the treatment regimen of lenalidomide and dexamethasone reduced risk of death by 21% and extended OS by 7.9 months in patients with relapsed or refractory MM compared with patients on lenalidomide and dexamethasone alone.

According to Keith Stewart, MB, ChB, researcher at the Mayo Clinic in Arizona and principal investigator of the ASPIRE trial, the results validate the use of carfilzomib, lenalidomide, and dexamethasone as a “standard of care regimen” for relapsed or refractory MM.

"Furthermore, these data showed that early use of carfilzomib, lenalidomide, and dexamethasone at first relapse provided nearly 1 additional year of survival for patients regardless of prior treatment with bortezomib or transplant,” Stewart said in a statement.

The trial results showed that at first relapse, patients on carfilzomib, lenalidomide, and dexamethasone had an OS improvement of 11.4 months. The final analysis of ASPIRE included subgroup analyses by prior lines of therapy, prior bortezomib exposure at first relapse, and prior transplant at first relapse. Reduction in death risk among the 3 groups was consistent with findings in the overall population.

"As seen in 2 different phase 3 studies, Kyprolis-based regimens are the first and only therapy combinations to demonstrate a significant overall survival advantage for patients with relapsed or refractory multiple myeloma versus recent standards of care," said Reese.