title: A phase 1 study of bendamustine and melphalan conditioning for autologous stem cell transplantation in multiple myeloma.
abstract: Bendamustine has efficacy in multiple myeloma with a toxicity profile limited to myelosuppression. We hypothesized that adding bendamustine to autologous stem cell transplant conditioning in myeloma would enhance response without significant additional toxicity. We conducted a phase 1 trial adding escalating doses of bendamustine to the current standard conditioning of melphalan 200 mg/m(2). Twenty-five subjects were enrolled into 6 cohorts. A maximum tolerated dose was not encountered and the highest dose level cohort of bendamustine 225 mg/m(2) + melphalan 200 mg/m(2) was expanded to further evaluate safety. Overall, there was no transplant related mortality and only one grade 4 dose-limiting toxicity was observed. Median number of days to neutrophil and platelet engraftment were 11 (range, 9 to 14) and 13 (range, 10 to 21), respectively. Disease responses at day +100 posttransplantation were progression in 5 (21%), partial response in 1 (4%), very good partial response in 7 (33%), complete response in 1 (4%), and stringent complete response in 9 (38%). Six patients (24%) with pre-existing high-risk disease died from progressive myeloma during study follow-up, all at or beyond 100 days after autologous stem cell transplant. Bendamustine up to a dose of 225 mg/m(2) added to autologous stem cell transplantation conditioning with high-dose melphalan in patients with multiple myeloma did not exacerbate expected toxicities.
authors: Department of Medicine, Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY, USA. tom9009@med.cornell.edu
authors: Tomer M
authors: TM
authors: Mark
authors: Whitney
authors: W
authors: Reid
authors: Ruben
authors: R
authors: Niesvizky
authors: Usama
authors: U
authors: Gergis
authors: Roger
authors: R
authors: Pearse
authors: Sebastian
authors: S
authors: Mayer
authors: June
authors: J
authors: Greenberg
authors: Morton
authors: M
authors: Coleman
authors: Koen
authors: K
authors: Van Besien
authors: Tsiporah
authors: T
authors: Shore
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069461:Bendamustine Hydrochloride; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous
chemical_list: D009588:Nitrogen Mustard Compounds; D000069461:Bendamustine Hydrochloride; D008558:Melphalan