Efficacy and safety of carfilzomib for the treatment of multiple myeloma: An overview of systematic reviews.

In this overview we present a summary of evidence from systematic reviews (SRs) on the safety and efficacy of carfilzomib in multiple myeloma (MM). Our search in electronic databases and conference proceedings yielded 14 eligible SRs, graded as of low overall quality with the AMSTAR-2 tool. The Corrected Covered Area index was 52.3% which shows very high overlap among studies. Carfilzomib was shown to increase progression free survival (HR=0.61, 95%CI=0.47-0.78, p = 0.01, I =73%), overall survival (HR=0.79,95%CI=0.66-0.95, p = 0.01, I =0) and overall response rate (OR=2.4,95% CI=1.6-3.4, p < 0.001, I =99%) in relapsed/refractory MM (RRMM); all with moderate quality of evidence assessed with the GRADE approach. Carfilzomib was associated with cardiovascular adverse events (AEs) (RR=2.2, 95%CI=1.6-2.9, p < 0.001, I =0), nephrotoxicity (RR=1.79, 95% CI=1.43-2.23, p < 0.001, I =39%) and serious infections (RR=1.40, 95%CI=1.17-1.69, p < 0.001, I =57%). Concluding, carfilzomib is effective in RRMM, but associated with certain AEs. More randomized clinical trials and high-quality SRs, especially on newly diagnosed patients are needed.