Final results of a phase II PETHEMA trial of alternating bortezomib and dexamethasone as induction regimen prior autologous stem cell transplantation (ASCT) in younger patients with multiple myeloma (MM): Efficacy and clinical implications of tumor response

Abstract

8024 Background: Dexamethasone-based combinations are the standard induction regimens for younger patients with MM prior ASCT. This is the first study in which bortezomib and dexamethasone were administered on an alternating basis. Aims: efficacy and kinetics of response. Methods: patients with newly diagnosed MM under the age of 66 years were treated with bortezomib at 1.3 mg/m2 on days 1, 4, 8 and 11 (cycles 1, 3, 5) and dexamethasone 40 mg p.o. on days 1–4, 9–12 and 17–20 (cycles 2, 4 and 6), followed by ASCT with melphalan-200. Responses were evaluated by the EBMT criteria but a VGPR was included. Random effects models were utilized to analyze the tumor response kinetics to bortezomib and dexamethasone with the absolute value of M-protein overtime and decrease by cycle. Because the nonlinearity in the change of M-protein overtime, a piecewise linear model was employed. Results: between August, 2005 and March, 2006, 40 patients (median age 57) were enrolled. The response rate was 82% with 12% CR plus 10% VGPR. The response was quick with 82% M-protein reduction achieved with the first 2 cycles. There was no further decrease of the mean M-protein in cycles 5 and 6. The M-protein decrease was not different with dexamethasone and with bortezomib (p=0.48). Chromosome 13 deletion as well as t(4;14) and t(14;16) did not had a negative impact on response. Toxicity was very low: ten (25%) patients had mild peripheral neuropathy (grade 1:9 cases, grade 2:1 case) and 11 grade 1 thrombocytopenia. Grade 3 toxicity was observed in 7 patients (neutropenia 6, skin/liver 1 case). No patient developed grade 4 toxicity. In all patients stem cells could be adequately collected (median of CD34+ 5 ×106/Kg). The overall response rate after ASCT was 90% with 40% CR plus 20% VGPR. Conclusions: Bortezomib alternating with dexamethasone is highly effective as up-front therapy in patients with MM, and is associated with a very low toxicity. The results of the tumor response kinetics analysis support a short program of alternating bortezomib and dexamethasone (i.e., maximum of 4 cycles) as an effective and safe therapy for younger myeloma patients prior ASCT. [Table: see text]