A final analysis of the phase 3 ASPIRE trial showed that adding carfilzomib (Kyprolis, Amgen) to lenalidomide and dexamethasone reduced the risk of death by 21% versus lenalidomide and dexamethasone alone in patients with relapsed or refractory multiple myeloma, Amgen announced.
The analysis, published in the Journal of Clinical Oncology, found that the carfilzomib, lenalidomide, and dexamethasone regimen (KRd) extended OS by 7.9 months, to a median of 48.3 months, versus 40.4 months for lenalidomide and dexamethasone alone (Rd) (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.67–0.95; one-sided P = 0.0045). Notably, an OS improvement of 11.4 months was seen patients at first relapse (47.3 versus 35.9 months [HR, 0.81; 95% CI, 0.62–1.06]), supporting early use of KRd.
The results “further validate carfilzomib, lenalidomide and dexamethasone as a standard of care regimen for patients with relapsed or refractory multiple myeloma," said Keith Stewart, MB, ChB, Mayo Clinic in Arizona and principal investigator of the ASPIRE trial. "Furthermore, these data showed that early use of carfilzomib, lenalidomide, and dexamethasone at first relapse provided nearly one additional year of survival for patients regardless of prior treatment with bortezomib or transplant."
The safety data from ASPIRE was consistent with the known safety profile of carfilzomib. The most common adverse events (greater than or equal to 20%) in the carfilzomib arm were diarrhea, anemia, neutropenia, fatigue, upper respiratory tract infection, pyrexia, cough, hypokalemia, thrombocytopenia, muscle spasms, pneumonia, nasopharyngitis, nausea, constipation, insomnia, and bronchitis.
The final analysis of ASPIRE included subgroup analyses by prior lines of therapy, prior bortezomib (Velcade, Millenium Pharmaceuticals) exposure at first relapse, and prior transplant at first relapse. Among these three groups, there was an 18% to 29% reduction in the risk of death for KRd versus Rd, consistent with findings in the overall population.
Median OS was 11.4 months longer for KRd versus Rd in patients who had received one prior line of therapy and 6.5 months longer for patients with two or more prior lines (48.8 versus 42.3 months [HR, 0.79; 95% CI, 0.62–0.99]). Among patients who had received one prior line, median OS was improved by 12 months with KRd versus Rd in those with prior bortezomib exposure (45.9 versus 33.9 months [HR, 0.82; 95% CI, 0.56–1.19]) and by 7.9 months in those without prior bortezomib (48.3 versus 40.4 months [HR, 0.80, 95% CI, 0.55–1.17]). Median OS was also improved by 18.6 months with KRd versus Rd among patients with prior transplantation at first relapse (57.2 versus 38.6 months [HR, 0.71, 95% CI, 0.48–.05]).
Amgen has submitted a supplemental new drug application to the FDA to include the OS data from ASPIRE in the product information for KYPROLIS.
Source: Amgen; January 17, 2018.