Randomized phase 3 study of carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible, NDMM patients
Facon T (1), Lee JH (2), Moreau P (3), Niesvizky R (4), Dimopoulos M (5), Hajek R (6), Pour L (7), Jurczyszyn A (8), Qiu L (9), Klippel Z (10), Zahlten-Kumeli A (10), Osman M (10), Paiva B (11), San-Miguel J (11).
(1) CHRU Lille Hopital Claude Huriez, Lille, France
(2) Gachon University Gil Medical Center, Incheon, Korea, Republic of.
(3) University of Nantes, Nantes, France.
(4) Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, United States.
(5) National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
(6) University Hospital Ostrava and Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic.
(7) University Hospital Brno, Brno, Czech Republic.
(8) Jagiellonian University, Krakow, Poland.
(9) Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC State Key Lab of Experimental Hematology, Tianjin, China.
(10) Amgen Inc., Thousand Oaks, CA, United States.
(11) Clinica Universidad de Navarra-Centro de Investigacion Medica Aplicada, IDISNA, CIBERONC, Pamplona, Spain.
Date: Feb 28, 2019Hematología y Hemoterapia [SP]
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.
CITATION Blood. 2019 Feb 28. pii: blood-2018-09-874396. doi: 10.1182/blood-2018-09-874396
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