title: A phase 2 single-center study of carfilzomib 56 mg/m2 with or without low-dose dexamethasone in relapsed multiple myeloma.
abstract: Standard carfilzomib (20 mg/m(2) cycle 1, 27 mg/m(2) thereafter; 2- to 10-minute infusion) is safe and effective in relapsed or refractory multiple myeloma (R/RMM). We report phase 2 results of carfilzomib 20 mg/m(2) on days 1 to 2 of cycle 1, 56 mg/m(2) thereafter (30-minute infusion), in R/RMM with the option of adding dexamethasone (20 mg) for suboptimal response/progression. Forty-four patients enrolled, all having prior bortezomib and immunomodulatory drugs and a median of 5 prior regimens. Of 42 response-evaluable patients, 23 (55%) achieved at least partial response (PR). Median (95% confidence interval) duration of response, progression-free, and overall survival were 11.7 (6.7-14.7), 4.1 (2.5-11.8), and 20.3 months (6.4-not estimable), respectively. High-risk cytogenetics did not impact outcomes. Treatment was active in bortezomib-refractory subgroups, but these patients tended to have poorer outcomes. Four/10 patients with prior allogeneic transplant achieved at least PR. Of 6 patients who responded, progressed and had dexamethasone added, 4 achieved at least stable disease. The most frequent grade 3/4 adverse events (AEs) possibly related to carfilzomib included lymphopenia (43%), thrombocytopenia (32%), hypertension (25%), pneumonia (18%), and heart failure (11%). Seven patients (16%) discontinued treatment due to AEs. Carfilzomib 56 mg/m(2) ± dexamethasone was tolerable and provided durable responses. This trial was registered at www.clinicaltrials.gov as #NCT01351623.
authors: Myeloma Service, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Medicine, Weill Medical College of Cornell University, New York, NY; and.
authors: Nikoletta
authors: N
authors: Lendvai
authors: Epidemiology and Biostatistics.
authors: Patrick
authors: P
authors: Hilden
authors: Epidemiology and Biostatistics.
authors: Sean
authors: S
authors: Devlin
authors: Department of Medicine, Weill Medical College of Cornell University, New York, NY; and Adult Bone Marrow Transplantation Service.
authors: Heather
authors: H
authors: Landau
authors: Myeloma Service, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Medicine, Weill Medical College of Cornell University, New York, NY; and.
authors: Hani
authors: H
authors: Hassoun
authors: Myeloma Service, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Medicine, Weill Medical College of Cornell University, New York, NY; and.
authors: Alexander M
authors: AM
authors: Lesokhin
authors: Department of Medicine, and.
authors: Ioanna
authors: I
authors: Tsakos
authors: Department of Medicine, and.
authors: Kaitlyn
authors: K
authors: Redling
authors: Department of Medicine, Weill Medical College of Cornell University, New York, NY; and Adult Bone Marrow Transplantation Service.
authors: Guenther
authors: G
authors: Koehne
authors: Department of Medicine, Weill Medical College of Cornell University, New York, NY; and Adult Bone Marrow Transplantation Service.
authors: David J
authors: DJ
authors: Chung
authors: Department of Medicine, Weill Medical College of Cornell University, New York, NY; and Cardiology Service, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors: Wendy L
authors: WL
authors: Schaffer
authors: Department of Medicine, Weill Medical College of Cornell University, New York, NY; and Adult Bone Marrow Transplantation Service.
authors: Sergio A
authors: SA
authors: Giralt
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000235:genetics; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects; D011719:Pyrazines / Q000627:therapeutic use; D012307:Risk Factors; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D009842:Oligopeptides; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; C524865:carfilzomib; D003907:Dexamethasone; D000077269:Lenalidomide