Τίτλος:
Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Facon, T.
Lee, J.H.
Moreau, P.
Niesvizky, R.
Dimopoulos, M.
Hajek, R.
Pour, L.
Jurczyszyn, A.
Qiu, L.
Klippel, Z.
Zahlten-Kumeli, A.
Osman, M.
Paiva, B.
San-Miguel, J.
Περιοδικό:
Blood advances
Εκδότης:
American Society of Hematology
Λέξεις-κλειδιά:
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
DOI:
10.1182/blood-2018-09-874396
