TY - JOUR
TI - Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma
AU - Facon, T.
AU - Lee, J.H.
AU - Moreau, P.
AU - Niesvizky, R.
AU - Dimopoulos, M.
AU - Hajek, R.
AU - Pour, L.
AU - Jurczyszyn, A.
AU - Qiu, L.
AU - Klippel, Z.
AU - Zahlten-Kumeli, A.
AU - Osman, M.
AU - Paiva, B.
AU - San-Miguel, J.
JO - Blood advances
PY - 2019
VL - 133
TODO - 18
SP - 1953-1963
PB - American Society of Hematology
SN - null
TODO - 10.1182/blood-2018-09-874396
TODO - bortezomib;  carfilzomib;  melphalan;  prednisone;  antineoplastic agent;  bortezomib;  carfilzomib;  melphalan;  oligopeptide;  prednisone, acute kidney failure;  aged;  anemia;  Article;  asthenia;  constipation;  controlled study;  coughing;  decreased appetite;  diarrhea;  drug dose increase;  drug dose reduction;  drug safety;  dyspnea;  European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30;  fatigue;  female;  fever;  heart failure;  human;  hypertension;  hypokalemia;  hyponatremia;  hypotension;  insomnia;  ischemic heart disease;  kidney failure;  leukopenia;  lung infection;  lymphocytopenia;  major clinical study;  male;  minimal residual disease;  multicenter study;  multiple cycle treatment;  multiple myeloma;  nausea;  neuralgia;  neutropenia;  overall survival;  peripheral edema;  peripheral neuropathy;  phase 3 clinical trial;  pneumonia;  polyneuropathy;  priority journal;  progression free survival;  quality of life;  quality of life assessment;  randomized controlled trial;  rash;  sensory neuropathy;  thrombocytopenia;  treatment duration;  treatment response;  upper respiratory tract infection;  vomiting;  adult;  clinical trial;  middle aged;  mortality;  multiple myeloma;  treatment outcome;  very elderly, Adult;  Aged;  Aged, 80 and over;  Antineoplastic Combined Chemotherapy Protocols;  Bortezomib;  Female;  Humans;  Male;  Melphalan;  Middle Aged;  Multiple Myeloma;  Oligopeptides;  Prednisone;  Progression-Free Survival;  Treatment Outcome
TODO - 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; 36mg/m2 there after) or bortezomibon 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). Nine hundred fifty-five patients were randomized (intention-to-treat population: KMP, n 5 478; VMP, n 5 477). 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 5. 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 peripheral neuropathy 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. © 2019 by The American Society of Hematology.
ER -