Siegel DS, et al. - The ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd) vs lenalidomide plus dexamethasone (Rd) among patients with relapsed or refractory multiple myeloma demonstrated significantly improved progression-free survival in the carfilzomib group. The final overall survival (OS) data and updated safety results were reported in this study. Findings revealed a statistically significant and clinically meaningful reduction in the risk of death with KRd vs Rd. It improved survival by 7.9 months. At first relapse, the KRd efficacy advantage was most pronounced.

Methods

• Adults with relapsed multiple myeloma (one to three prior lines of therapy) were eligible.
• Researchers randomized the patients at a 1:1 ratio to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease progression, or occurrence of unacceptable toxicity.
• All patients received Rd only after 18 cycles.
• Primary end point included progression-free survival.
• OS was assessed as the secondary end point.
• Comparison of OS was performed between treatment arms using a stratified log-rank test.

Results

• For KRd vs Rd, median OS was 48.3 months (95% CI, 42.4 to 52.8 months) vs 40.4 months (95% CI, 33.6 to 44.4 months) (hazard ratio, 0.79; 95% CI, 0.67 to 0.95; one-sided P=.0045).
• Median OS was 11.4 months longer for KRd vs Rd among patients receiving one prior line of therapy; it was 6.5 months longer for KRd vs Rd among patients receiving ≥ two prior lines of therapy.
• Because of adverse events (AEs), treatment discontinuation rates were 19.9% (KRd) and 21.5% (Rd).
• Researchers noticed that grade ≥ 3 AE rates were 87.0% (KRd) and 83.3% (Rd).
• For KRd vs Rd group, selected grade ≥ 3 AEs of interest were acute renal failure (3.8% vs 3.3%), cardiac failure (4.3% vs 2.1%), ischemic heart disease (3.8% vs 2.3%), hypertension (6.4% vs 2.3%), hematopoietic thrombocytopenia (20.2% vs 14.9%), and peripheral neuropathy (2.8% vs 3.1%).