Results of a phase I/II trial adding carmustine (300 mg/m2) to melphalan (200 mg/m2) in multiple myeloma patients undergoing autologous stem cell transplantation.

Autologous stem cell transplantation (SCT) with high-dose melphalan (HDM, 200 mg/m2) is the most effective therapy for multiple myeloma. To determine the feasibility of combining carmustine (300 mg/m2) with HDM, we enrolled 49 patients with previously treated Durie-Salmon stage II/III myeloma (32M/17W, median age 53) on a phase I/II trial involving escalating doses of melphalan (160, 180, 200 mg/m2). The median beta2-microglobulin was 2.5 (0-9.3); marrow karyotypes were normal in 88%. The phase I dose-limiting toxicity was > or =grade 2 pulmonary toxicity 2 months post-SCT. Other endpoints were response rate and progression-free survival (PFS). HDM was safely escalated to 200 mg/m2; treatment-related mortality was 2% and > or =grade 2 pulmonary toxicity 10%. The complete (CR) and near complete (nCR) response rate was 49%. With a median post-SCT follow-up of 2.9 years, the PFS and overall survival (OS) post-SCT were 2.3 and 4.7 years. PFS for those with CR or nCR was 3.1 years while for those with stable disease (SD) it was 1.3 years (P=0.06). We conclude that carmustine can be combined with HDM for myeloma with minimal pulmonary toxicity and a high response rate.

RCT Entities:   Population Interventions Outcomes