Efficacy and safety of carfilzomib in relapsed and/or refractory multiple myeloma: Systematic review and meta-analysis of 14 trials

Objective: Carfilzomib (Carf) is a second-generation proteasome inhibitor approved for patients with relapsed and/or refractory multiple myeloma (RRMM) who failed ≥ 1 prior lines of therapy. We performed a systematic review of Carf literature with meta-analysis to determine the efficacy and safety in RRMM patients. Methods: Based on literature search, we included a total of 14 eligible phase I/ II, phase II and phase III Carf based clinical trials. The cumulative incidence and odds ratios (OR) were calculated with random effect model, using ''R'' software with metaphor package. Results: 2906 evaluable RRMM patients from published clinical trials included. The pooled overall response rate (ORR) was 45% (95% CI: 29-62). The pooled clinical benefit rate (CBR) was 56% (95% CI: 41-71). OR from 3 randomized clinical trials showed that Carf significantly improved ORR and CBR compared to control groups (OR 2.4, P < 0.0001; 2.02, P = 0.0007, respectively). Subgroup analysis showed significantly better ORR (P < 0.0001) and CBR (P < 0.001) with combination regimens compared to monotherapy. Response was significantly higher with high dose of Carf (> 20/27 mg/m²) compared to standard dose (ORR 65% vs. 35%, P = 0.03). Compared to control group, the OR of developing cardiotoxicity (P = 0.002) and hypertension (P < 0.0001) were significantly higher with Carf, while no difference in peripheral neuropathy (P = 0.28). Conclusions: Carf produces significantly better responses with acceptable safety profile in RRMM patients. Combination regimens and higher dose Carf offers better response with no significant extra toxicity. Its efficacy is regardless of cytogenetics or disease stage. Incidences of cardiotoxicity and hypertension seem higher with Carf.