A Phase 1 Study of Intravenous Busulfan as a Conditioning Regimen forMultiple Myeloma

摘要

The efficacy of melphalan (MEL) 140 mg/m pre-transplant conditioning versusMEL 200 mg/m for the elderly is still debated. We hypothesized thatsingle-agent intravenous busulfan (BU) would show significant anti-myeloma efficacy and bebetter tolerated by elderly patients. A prospective 3+3 dose escalation study enrolledsymptomatic multiple myeloma (MM) patients 65 years or older with SWOG performance 0–2 fortreatment with intravenous BU pre-transplant at different administration levels. Theprimary objective was to determine the maximum tolerated dose (MTD) of BU that could besafely given over the least number of days. All patients, except one, received maintenancetreatment post-transplant, mostly for 2 years. We enrolled 13 patients, mean age of 73years (range 68–80). Pharmacokinetic analysis showed no greater than 2% accumulation inthe 13 patients, confirming a lack of accumulation in the multi-dose regimen. No deathsoccurred in the peri-transplant period. Grade 3/4 adverse effects were hematological, nodose-limiting toxicity was observed and MTD was not reached. Three patients developedgrade 3 mucositis but none developed veno-occlusive disease. Ten (77%) patients achieved acomplete remission (CR) post-transplant with a remarkably long average time to bestresponse of 6.7 months (range: 6–14 m), and two attained a partial response. Medianoverall survival was 84 months (95% CI, 21–104) and the median progression-free survivalwas 60 months (95% CI, 9–93). Our results suggest that IV BU could be an alternativeconditioning regimen to MEL 140 in elderly patients with MM, and supports futurerandomized trials.