Abstract
The overall survival of patients with advanced MM undergoing high-dose chemotherapy depends mainly on the quality of response. Thus, to improve the response rate, modifications of high dose therapy have been evaluated to prolong survival. In this randomised phase III study 2 strategies to improve response rates were compared: tandem high dose melphalan and an intensified chemoradiotherapy. Tandem high dose chemotherapy was shown to be superior to single high dose chemotherapy in a recent study. In a phase I/II study we showed modified total body irradiation, busulfan and cyclophosphamide to induce a high CR rate (48%). Thus, in this phase III study, tandem high dose melphalan was compared to radiochemotherapy with TMI/Bu/Cy. 294 patients with age <60 years with MM underwent induction (VAD or ID) and mobilization chemotherapy (IEV). After 4 cycles of idarubicine/dexamethason in 160 patients 6% achieved a CR, 62% a PR, 15 % a MR, 12% SD and 5% PD. 51 patients underwent FISH analysis: 9/18 patients with and 20/33 without 13q deletion achieved PR/CR after induction (P=0.47). After achieving at least SD 198 patients proceeded to high-dose therapy followed by autologous SCT. Toxicity was higher after TMI/Bu/Cy vs Mel 200 with more mucositis grade III/IV (93 vs 66%) and infections (79% vs 68%). But TRM was 3% following TMI/Bu/Cy vs 4% after tandem-HD melphalan therapy. The PCR/CR-rate of TMI/Bu/Cy and Tandem-Mel 200 was 80 vs. 86%, median PFS 31.2 vs 25.9 (p=0.258).
Thus, the higher organ toxicity following the intensified conditioning regimen does not result in a higher TRM when compared to tandem-melphalan. With a still short follow up of 4 years no significant difference in PFS is demonstrated between a single course of high dose chemoradiotherapy and tandem high dose melphalan therapy.
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