A Phase 1 Study of Bendamustine and Melphalan Conditioning for Autologous Stem Cell Transplantation in Multiple Myeloma

摘要

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 200mg/m². Twenty-five subjects were enrolled onto 6 cohorts. A maximum tolerated dose was not encountered and the highest dose level cohort of bendamustine 225mg/m² + melphalan 200mg/m² was expanded to further evaluate safety. Overall, there was no transplant related mortality and only 1 grade 4 dose-limiting toxicity was observed. Median number of days to neutrophil and platelet engraftment was 11 (9-14) and 13 (10-21), respectively. Disease responses at day +100 post-transplant 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 preexisting high-risk disease died from progressive myeloma during study follow-up, all at or beyond 100 days after ASCT. Bendamustine up to a dose of 225mg/m² added to autologous stem cell transplant conditioning with high dose melphalan in multiple myeloma did not exacerbate expected toxicities.