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Trends in pre- and post-transplant therapies with first autologous hematopoietic cell transplantation among patients with multiple myeloma in the United States, 2004–2014

Leukemia volume 31, pages 1998–2000 (2017)Cite this article

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Multiple myeloma (MM), the second most common hematologic malignancy in adults with an estimated ~30 000 new cases in the United States each year1 has seen remarkable improvements in survival since the turn of the century.2 These improvements are in a large part related to the availability and use of novel therapies such as proteasome inhibitors and immunomodulatory drugs, as well as novel treatment paradigms such as upfront autologous hematopoietic cell transplantation (AHCT), post-transplant consolidation and/or maintenance therapies within the last decade. Upfront AHCT remains the standard-of-care in transplant-eligible patients.3, 4 We analyzed trends in pre- and post-transplant therapies and survival outcomes among patients undergoing AHCT for MM in the United States (US) using the Center for International Blood and Marrow Transplant Research (CIBMTR) database. The purpose of this analysis was to show real-world trends in patients, induction chemotherapies and post-transplant treatments in the US during a period which has seen several paradigm changes in multiple myeloma management.

This study was approved by the Institutional Review Board of the Medical College of Wisconsin. First single AHCT in the US (n=37 705) using high-dose melphalan for MM of consented patients and reported to the CIBMTR, 2004–2014 was included and a representative subset (n=5 077) with detailed research level data were studied in sub-analyses. Data on use of individual chemotherapies for induction and post-transplant therapies were obtained (vincristine/adriamycin/dexamethasone, VAD; thalidomide, T; lenalidomide, R; bortezomib, V; cyclophosphamide, C; dexamethasone, D and the combinations TD, RD, VD, VTD, VCD and VRD). Trends were studies in 3 time cohorts based on year of transplant: 2004–2007, 2008/09, and 2010–14. These periods were determined based on meaningful changes that occurred with induction and maintenance treatments, 2004–2007 (VAD and TD induction, no V/R maintenance), 2008–2009 (doublets and triplets with V and/or R) and 2010–2014 (novel triplet and R maintenance). During this period, the CIBMTR captured 60–80% of all AHCT activity for MM in the US. Demographic, disease-related and treatment-related data were analyzed. Post-transplant therapy was defined as immediate post-AHCT therapy used in the absence of relapse and/or progression of MM; in this setting it captures both consolidation and maintenance. Data on post-transplant therapies were available after 2008. Kaplan–Meier method was used to conduct survival analysis; the median progression-free (PFS) and overall (OS) survival analysis were compared in the years 2004–2007, 2008–2009, 2010–2014. Multivariate analysis was performed using Cox proportional hazards method. The year of transplant group was the main effect; age, Karnofsky performance score (KPS), advanced stage at diagnosis (ISS III and/or DSS III), time from diagnosis to transplant, number of chemotherapy regimens prior to transplant, disease status prior to transplant and melphalan conditioning dose were also factored in the model. Both pre-transplant and post-transplant therapies were not further analyzed in the models as these variables were confounded by close correlation with the ‘year of transplant’ variable. Further, post-transplant therapies were only available during a portion of this study.

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Acknowledgements

This publication is funded in part by the Research and Education Program Fund, a component of the Advancing a Healthier Wisconsin endowment at the Medical College of Wisconsin and by KL2TR001438 from the Clinical and Translational Science Award program of the National Center for Advancing Translational Sciences (AD). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

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  1. Department of Medicine, Center for International Blood and Transplant Research, Medical College of Wisconsin, Milwaukee, 53226, WI, USA

    A D'Souza, M-J Zhang, J Huang, M Fei, M Pasquini, M Hamadani & P Hari

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  1. A D'Souza
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Correspondence to A D'Souza.

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D'Souza, A., Zhang, MJ., Huang, J. et al. Trends in pre- and post-transplant therapies with first autologous hematopoietic cell transplantation among patients with multiple myeloma in the United States, 2004–2014. Leukemia 31, 1998–2000 (2017). https://doi.org/10.1038/leu.2017.185

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