Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (< 24 months), and to identify factors predicting for early vs late relapses (24−48 months post-AHCT). Over three periods (2001–2004, 2005–2008, 2009–2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35–38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky < 90, stage III, > 1 line of induction and lack of maintenance. Post-AHCT early relapse remains a poor prognostic factor, even though outcomes have improved over time.
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The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement 5U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-15-1-0848 and N00014-16-1-2020 from the Office of Naval Research; and grants from Alexion; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; AstraZeneca; Be the Match Foundation; Bluebird Bio, Inc.; Bristol Myers Squibb Oncology; Celgene Corporation; Cellular Dynamics International, Inc.; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Genentech, Inc.; Genzyme Corporation; Gilead Sciences, Inc.; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Janssen Scientific Affairs, LLC; Jazz Pharmaceuticals, Inc.; Jeff Gordon Children’s Foundation; The Leukemia & Lymphoma Society; Medac, GmbH; MedImmune; The Medical College of Wisconsin; Merck & Co, Inc.; Mesoblast; MesoScale Diagnostics, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Neovii Biotech NA, Inc.; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Otsuka Pharmaceutical Co, Ltd. – Japan; PCORI; Perkin Elmer, Inc.; Pfizer, Inc; Sanofi US; Seattle Genetics; Spectrum Pharmaceuticals, Inc.; St. Baldrick’s Foundation; Sunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Takeda Oncology; Telomere Diagnostics, Inc.; University of Minnesota; and Wellpoint, Inc.
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 (D’Souza, A).
Supplementary Information accompanies this paper on the Leukemia website (http://www.nature.com/leu).
Kumar, Shaji K.; Dispenzieri, Angela; Fraser, Raphael; Mingwei, Fei; Akpek, Gorgun; Cornell, Robert; Kharfan-Dabaja, Mohamed; Freytes, Cesar; Hashmi, Shahrukh; Hildebrandt, Gerhard C.; Holmberg, Leona; Kyle, Robert; Lazarus, Hillard; Lee, Cindy; Mikhael, Jospeh; Nishihori, Taiga; Tay, Jason; Usmani, Saad; Vesole, David; Vij, Ravi; Wirk, Baldeep; Krishnan, Amrita; Gasparetto, Cristina; Mark, Tomer; Nieto, Yago; Hari, Parameswaran; and D'Souza, Anita, "Early Relapse After Autologous Hematopoietic Cell Transplantation Remains a Poor Prognostic Factor in Multiple Myeloma but Outcomes Have Improved Over Time" (2018). Internal Medicine Faculty Publications. 187.