title: Phase I/II trial assessing bendamustine plus bortezomib combination therapy for the treatment of patients with relapsed or refractory multiple myeloma.
abstract: Bendamustine, active in multiple myeloma (MM), is a bifunctional mechlorethamine derivative with alkylating properties. Bortezomib, approved to treat MM, is effective in combination with alkylators. The tolerability and efficacy of bendamustine plus bortezomib in relapsed/refractory MM was assessed in an open-label, dose-escalating, phase I/II study. Patients aged ≥18 years received intravenous bendamustine 50, 70, or 90 mg/m(2)  (days 1 and 4) plus bortezomib 1·0 mg/m(2)  (days 1, 4, 8, and 11) for up to eight 28-day cycles. No dose-limiting toxicity was observed after cycle 1; bendamustine 90 mg/m(2)  plus bortezomib 1·0 mg/m(2)  was designated the maximum tolerated dose (MTD). The most common grade 3/4 adverse events were leucopenia (58%), neutropenia (50%), lymphopenia (45%), and thrombocytopenia (30%). Primary efficacy measure was overall response rate (ORR), which was the combined complete response (CR), very good partial response (VGPR), partial response (PR), and minimal response (MR). ORR was 48% (one CR, two VGPR, nine PR, and seven MR) for all 40 enrolled patients, 52% (16/31) at the MTD (90 mg/m(2) ), and 42% and 46% for prior use of bortezomib (n = 31) or alkylators (n = 28) respectively. Bendamustine plus bortezomib was well tolerated with promising efficacy in this heavily pretreated population.
authors.affiliation: Oncotherapeutics, Institute for Myeloma & Bone Cancer Research, 9201 W. Sunset Blvd, West Hollywood, CA 90069, USA. jberenson@imbcr.org
authors.forename: James R
authors.initials: JR
authors.lastname: Berenson
authors.forename: Ori
authors.initials: O
authors.lastname: Yellin
authors.forename: Alberto
authors.initials: A
authors.lastname: Bessudo
authors.forename: Ralph V
authors.initials: RV
authors.lastname: Boccia
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Noga
authors.forename: Donald S
authors.initials: DS
authors.lastname: Gravenor
authors.forename: Dipti
authors.initials: D
authors.lastname: Patel-Donnelly
authors.forename: Robert S
authors.initials: RS
authors.lastname: Siegel
authors.forename: Tarun
authors.initials: T
authors.lastname: Kewalramani
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gorak
authors.forename: Youram
authors.initials: Y
authors.lastname: Nassir
authors.forename: Regina A
authors.initials: RA
authors.lastname: Swift
authors.forename: Debra
authors.initials: D
authors.lastname: Mayo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D009588:Nitrogen Mustard Compounds; D011719:Pyrazines; D000069286:Bortezomib; D000069461:Bendamustine Hydrochloride