Abstract
Incorporation of novel agents into auto-SCT for patients with multiple myeloma has led to improvement in their outcomes. However, the effects of new drugs, either single or combined, on PBSC mobilization have not been fully evaluated, particularly in phase 3 clinical studies. We analyzed the impact of two novel agent-based induction treatments in patients enrolled in the GIMEMA MMY-3006 study comparing bortezomib, thalidomide and dexamethasone (VTD) versus thalidomide and dexamethasone (TD) in preparation for double auto-SCT. Results showed that a short-term induction therapy with VTD did not adversely affect CD34+ cell yields as compared with TD (9.75 vs 10.76 × 106 CD34+ cells/kg, P=0.220). For poor mobilizers (<4 × 106 CD34+ cells/kg), 5-year rates of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) were significantly shorter than for successful mobilizers (TTP:17 vs 48%, P<0.0001; PFS: 16 vs 46%, P<0.0001; OS: 50 vs 80%, P<0.0001). These differences were retained across patients randomized to the TD arm; conversely, no differences in outcomes were seen in patients treated with VTD, irrespective of the number of harvested CD34+ cells. The number of collected PBSCs predicted better outcomes after auto-SCT and VTD overcame the negative impact of a poor stem cell mobilization.
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Acknowledgements
This study was funded and sponsored by the Seràgnoli Institute of Hematology at the University of Bologna, Bologna, Italy. The study was partly supported by Janssen providing bortezomib free of charge, by the University of Bologna through a grant to MC (Ricerca Fondamentale Orientata), and by BolognaAIL. FED is a Cancer Research UK Senior Clinical Fellow.
Author Contributions
MC was the principal investigator and takes primary responsibility for the paper; AB, GP and MC designed the research and wrote the paper; AB, GP and APe performed the analysis; FP, FN, FB, SR, LC, SV, AML, MB and APa were the subinvestigators of the study and recruited the patients; PT, BAZ, EZ and KM provided patients and collected the data; MRM and SR performed cell laboratory work and collected the data; FED and GJM provided important intellectual inputs.
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AB has received honoraria from Celgene, MC has received honoraria and served on speakers’ bureaux for Janssen-Cilag, Millennium Pharmaceuticals, Celgene and Novartis and has been a consultant for Janssen-Cilag and Millennium Pharmaceuticals. FP has received honoraria from Janssen-Cilag, Celgene, Schering-Plough and Roche; AP has served on an advisory committee for Celgene, Janssen-Cilag, Amgen, Bristol-Myers Squibb, Millenium and Onyx and has received honoraria from Celgene, Janssen-Cilag, Bristol-Myers Squibb, Millenium, Onyx and Amgen; MB has received honoraria from Novartis and Bristol-Myers Squibb. The remaining authors declare no conflict of interest.
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Brioli, A., Perrone, G., Patriarca, F. et al. Successful mobilization of PBSCs predicts favorable outcomes in multiple myeloma patients treated with novel agents and autologous transplantation. Bone Marrow Transplant 50, 673–678 (2015). https://doi.org/10.1038/bmt.2014.322
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DOI: https://doi.org/10.1038/bmt.2014.322
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