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Randomized phase 3 study of carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible, NDMM patients

Thierry Facon, Jae Hoon Lee, Philippe Moreau, Ruben Niesvizky, Meletios Dimopoulos, Roman Hajek, Ludek Pour, Artur Jurczyszyn, Lugui Qiu, Zandra Klippel, Anita Zahlten-Kumeli, Muhtarjan Osman, Bruno Paiva and Jesus San-Miguel

Key points

  • Treatment with KMP vs VMP in transplant-ineligible NDMM patients resulted in similar PFS, with no statistically significant differences.

  • There was a trend for longer TTP in the KMP arm.

Abstract

The phase 3 CLARION study compared carfilzomib-melphalan-prednisone (KMP) with bortezomib-melphalan-prednisone (VMP) in transplant-ineligible newly-diagnosed multiple myeloma (NDMM) patients. Patients were randomized 1:1 to KMP or VMP for nine 42-day cycles (C). Patients received carfilzomib on days (D) 1, 2, 8, 9, 22, 23, 29, 30 (20 mg/m2: C1D1, C1D2; 36 mg/m2 thereafter) or bortezomib on D1, 4, 8, 11, 22, 25, 29, 32 (1.3 mg/m2; D4, 11, 25, 32 omitted for C5-9). Melphalan (9 mg/m2) and prednisone (60 mg/m2) were administered on D1-4. The primary endpoint was progression-free survival (PFS). 955 patients were randomized (intention-to-treat [ITT] population: KMP, n=478; VMP, n=477). Median PFS was 22.3 months with KMP vs 22.1 months with VMP (hazard ratio [HR], 0.906; 95% confidence interval [CI], 0.746-1.101; P = 0.159). Median overall survival was similar and not reached in either group (HR, 1.08; 95% CI, 0.82-1.43). Overall response rate was 84.3% for KMP and 78.8% for VMP. Complete response rate was 25.9% for KMP and 23.1% for VMP. Minimal residual disease-negative rates were 15.7% (KMP) and 15.5% (VMP). Adverse events (AEs) of interest (any grade) occurring with a ≥5% higher patient incidence in the KMP arm were acute renal failure (13.9% [KMP] vs 6.2% [VMP]) and cardiac failure (10.8% vs 4.3%). Grade ≥3 AE rates were 74.7% (KMP) and 76.2% (VMP). Grade ≥2 PN was lower for KMP vs VMP (2.5% vs 35.1%). Treatment with KMP in CLARION did not yield a statistically significant difference in PFS vs VMP. Registered at www.clinicaltrials.gov #NCT01818752.

  • Submitted September 11, 2018.
  • Accepted January 31, 2019.