title: An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib.
abstract: Carfilzomib is a next-generation proteasome inhibitor that selectively and irreversibly binds to its target. In clinical studies, carfilzomib has shown efficacy in patients with relapsed and/or refractory multiple myeloma (MM) and has demonstrated a tolerable safety profile. In this phase 2, open-label, multicentre clinical trial, 35 patients with relapsed and/or refractory MM following 1-3 prior therapies, including at least one bortezomib-based regimen, received carfilzomib 20 mg/m(2) in a twice-weekly, consecutive-day dosing schedule for ≤12 monthly cycles. The best overall response rate (ORR) was 17·1% and the clinical benefit response rate (ORR + minimal response) was 31·4%. The median duration of response was >10·6 months and the median time to progression was 4·6 months. The most common adverse events were fatigue (62·9%), nausea (60·0%), and vomiting (42·9%). No exacerbation of baseline peripheral neuropathy was observed. Single-agent carfilzomib was generally well tolerated for up to 12 treatment cycles and showed activity in patients with relapsed and/or refractory MM who had received prior treatment with bortezomib. These data, combined with an acceptable toxicity profile, support the potential use of carfilzomib in patients with relapsed and/or refractory MM and warrant continued investigation of carfilzomib as single agent or in combination with other agents.
authors: Washington University School of Medicine, St. Louis, MO 63110, USA. rvij@im.wustl.edu
authors: Ravi
authors: R
authors: Vij
authors: David S
authors: DS
authors: Siegel
authors: Sundar
authors: S
authors: Jagannath
authors: Andrzej J
authors: AJ
authors: Jakubowiak
authors: Alexander Keith
authors: AK
authors: Stewart
authors: Kevin
authors: K
authors: McDonagh
authors: Nizar
authors: N
authors: Bahlis
authors: Andrew
authors: A
authors: Belch
authors: Lori A
authors: LA
authors: Kunkel
authors: Sandra
authors: S
authors: Wear
authors: Alvin F
authors: AF
authors: Wong
authors: Michael
authors: M
authors: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use*; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D009842:Oligopeptides; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; C524865:carfilzomib