Oral presentation by Dr. Michele Cavo
There is still controversy regarding the role of tandem double autologous transplant (autoBMT) for eligible patients with de novo multiple myeloma. This study provides long-term follow-up of three phase III studies involving patients induced with bortezomib-based triplet therapy (VTD or PAD), followed by at least one autoBMT and consolidation and/or maintenance. Patients were assigned to receive a single or double autoBMT.
A total of 909 patients were randomized in the VTD or PAD arm and received either a single autoBMT (n= 501) or a double autoBMT (n = 408). The percentage of high-cytogenetic-risk patients was 18% in the single autoBMT group and 23% in the double autoBMT group.
After a considerably long follow-up (117 months), the progression-free survival (PFS) of patients in the double autoBMT group was 47 months versus 38 months for patients in the single autoBMT group (HR = 0.76; p = 0.0008). The probability of overall survival (OS) at 10 years was 58% versus 47% in favour of tandem transplantation. The benefits in terms of PFS favoured the double autoBMT group in the various subgroups, including standard cytogenetic risks (53 months vs. 43 months) and high cytogenetic risks (36 months vs. 20 months). In addition, the 10-year OS was 72% versus 60% for standard risk and 51% versus 34% for high-risk patients. In a multivariate analysis, predictive factors not associated with a prolonged PFS in the double autoBMT group were the International Staging System I and II score, the lack of translocation (4;14) and/or deletion of 17p, and achieving complete remission. Patients who did not have two or three of these elements (considered very high risk) had a clear benefit in terms of PFS and OS with a double autoBMT (PFS of 32 months vs. 20 months and 10-year OS of 43% vs. 20%).
This study confirms the role of tandem double autoBMT for patients at high risk. This study reveals very interesting survival data (58% at 10 years in the double autoBMT group). Although this study represents a blending of methodologies in terms of induction, consolidation and maintenance, I believe that the benefits of tandem double autoBMT remain irrefutable for selected patients. This study does not allow us to assess this strategy for other high-risk cytogenetic factors, including translocation (14;16), translocation (14;20), and chromosome 1 abnormalities.