title: Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study.
abstract: This multicenter phase 1/2 trial investigated the combination of bendamustine, lenalidomide, and dexamethasone in repeating 4-week cycles as treatment for relapsed refractory multiple myeloma (MM). Phase 1 established maximum tolerated dose (MTD). Phase 2 assessed overall response rate at the MTD. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). A total of 29 evaluable patients were enrolled. Median age was 63 years (range, 38-80 years). Median number of prior therapies was 3 (range, 1-6). MTD was bendamustine 75 mg/m(2) (days 1 and 2), lenalidomide 10 mg (days 1-21), and dexamethasone 40 mg (weekly) of a 28-day cycle. Partial response rate was 52%, with very good partial response achieved in 24%, and minimal response in an additional 24% of patients. Median follow-up was 13 months; median OS has not been reached. One-year OS is 93% (95% confidence interval [CI], 59%-99%). Median PFS is 6.1 months (95% CI, 3.7-9.4 months) with one-year PFS of 20% (95% CI, 6%-41%). Grade 3/4 adverse events included neutropenia, thrombocytopenia, anemia, hyperglycemia, and fatigue. This first phase 1/2 trial testing bendamustine, lenalidomide, and dexamethasone as treatment of relapsed refractory MM was feasible and highly active. This study is registered at www.clinicaltrials.gov as #NCT01042704.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine and Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Lentzsch
authors.forename: Amy
authors.initials: A
authors.lastname: O'Sullivan
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Kennedy
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abbas
authors.forename: Lijun
authors.initials: L
authors.lastname: Dai
authors.forename: Silvana Lalo
authors.initials: SL
authors.lastname: Pregja
authors.forename: Steve
authors.initials: S
authors.lastname: Burt
authors.forename: Michael
authors.initials: M
authors.lastname: Boyiadzis
authors.forename: G David
authors.initials: GD
authors.lastname: Roodman
authors.forename: Markus Y
authors.initials: MY
authors.lastname: Mapara
authors.forename: Mounzer
authors.initials: M
authors.lastname: Agha
authors.forename: John
authors.initials: J
authors.lastname: Waas
authors.forename: Yongli
authors.initials: Y
authors.lastname: Shuai
authors.forename: Daniel
authors.initials: D
authors.lastname: Normolle
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Zonder
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; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D009588:Nitrogen Mustard Compounds; D013792:Thalidomide; D003907:Dexamethasone; D000069461:Bendamustine Hydrochloride; D000077269:Lenalidomide