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Carfilzomib vs bortezomib in patients with multiple myeloma and renal failure: a subgroup analysis of ENDEAVOR

Meletios Dimopoulos, David Siegel, Darrell J. White, Ralph Boccia, Karim S. Iskander, Zhao Yang, Amy S. Kimball, Khalid Mezzi, Heinz Ludwig and Ruben Niesvizky

Key points

  • ENDEAVOR reported clinically meaningful PFS and OS improvements with Kd56 vs Vd in RRMM patients with varying degrees of renal impairment.

  • Patients with complete renal response had superior PFS and OS outcomes compared with non-responders across treatment groups.

Abstract

In ENDEAVOR, carfilzomib (56 mg/m2) and dexamethasone (Kd56) demonstrated longer progression-free survival (PFS) over bortezomib and dexamethasone (Vd) in patients with relapsed/refractory multiple myeloma (RRMM). Here we evaluated Kd56 vs Vd by baseline renal function in a posthoc exploratory subgroup analysis. The intent-to-treat population included 929 patients (creatinine clearance [CrCL] ≥15 to <50 mL/min: Kd56, n=85 and Vd, n=99; CrCL 50 to <80 mL/min: n=186 and 177; CrCL ≥80: n=193 and 189). In these subgroups, respectively, median (hazard ratio [HR; 95% confidence interval (CI)]) PFS was 14.9 (Kd56) vs 6.5 months (Vd; 0.49 [0.320–0.757]), 18.6 vs 9.4 months (0.48 [0.351–0.652]), and not reached (NR) vs 12.2 months (0.60 [0.434–0.827]). Median (HR [95% CI]) overall survival (OS) was 42.1 vs 23.7 months (0.66 [0.443–0.989]), 42.5 vs 32.8 months (0.83 [0.626–1.104]), and NR vs 42.3 months (0.75 [0.554–1.009]). Complete renal response (CrCL improvement to ≥60 mL/min in any 2 consecutive visits if baseline CrCL <50 mL/min) rates were 15.3% (Kd56; 95% CI, 8.4–24.7) and 14.1% (Vd; 95% CI, 8.0–22.6). In a combined Kd56 and Vd analysis, complete renal responders had longer median (HR [95% CI]) PFS (14.1 vs 9.4 months; 0.805 [0.438–1.481]) and OS (35.3 vs 29.7 months; 0.91 [0.524–1.577]) vs non-responders. Grade ≥3 adverse event rates in these subgroups (Kd56 vs Vd) were 87.1% vs 79.4%, 84.4% vs 71.8%, and 77.1% vs 65.9%. Thus, Kd56 demonstrated PFS and OS improvements over Vd in RRMM patients regardless of their baseline renal function.

  • Submitted June 28, 2018.
  • Accepted October 27, 2018.