A phase 1 study of bendamustine and melphalan conditioning for autologous stem cell transplantation in multiple...

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.