Two cycles of the PS-341/bortezomib, adriamycin, and dexamethasone combination followed by autologous hematopoietic cell transplantation in newly diagnosed multiple myeloma patients.

INTRODUCTION: Treatment with 3-6 cycles of PS-341/bortezomib, adriamycin, and dexamethasone (PAD) has been explored in terms of induction therapy prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). We evaluated the effects of two cycles of PAD given before ASCT.

PATIENTS AND METHODS: Patients received two 21-d cycles of PAD (bortezomib 1.3 mg/m(2) × 4 d, adriamycin 9 mg/m(2) × 4 d, and dexamethasone 40 mg × 4 d × 2). Starting on day 12 of cycle 2, patients were given subcutaneous granulocyte-colony stimulating factor to mobilize peripheral blood stem cells (PBSCs). Following PBSC harvesting, ASCT was performed using high-dose melphalan, followed by thalidomide.

RESULTS: A total of 32 patients were enrolled. Of 31 who completed two cycles of PAD, 25 (81%) achieved a partial response (PR) or better. Major adverse events were cytopenia, with grade I/II neurotoxicity evident during 4.8% of PAD cycles. Two patients were withdrawn from the study prior to PBSC collection. Thirty patients showed successful mobilization of PBSCs and underwent ASCT, with all 30 showing adequate neutrophil and platelet recovery. Following ASCT, 14 patients (47%) achieved a complete response (CR), 8 (27%) a very good partial response (VGPR), and 6 (20%) PR. Thalidomide was given to 25 patients after ASCT, as maintenance therapy. Twelve patients showed better responses after administration of thalidomide, and a total of 21 patients (70%) achieved CR. The 5-yr probabilities of overall and progression-free survival were 71.1% and 23.5%, respectively.

CONCLUSION: A short course of PAD was effective as an induction treatment before ASCT in patients newly diagnosed with MM. Prospective comparisons with longer courses of such treatment are needed.