International Differences in Baseline Characteristics and Practice Patterns in Patients with NEWLY Diagnosed Multiple Myeloma Undergoing Upfront Autologous STEM Cell Transplantation
Blood, vol. 140, pp. 5225–5227
Abstract
Background: Worldwide, patients with newly diagnosed multiple myeloma (NDMM) undergoing upfront autologous stem cell transplantation (ASCT) have different characteristics and survival outcomes, likely due to variances in transplant activity, patient and health economic factors including access to new myeloma therapies. The goal of this retrospective study was to analyze differences in regional outcomes. Methods: Data on patient characteristics and transplant outcomes for patients with NDMM who received an upfront ASCT between 2013 and 2017 were provided to the Worldwide Network for Blood and Marrow Transplantation (WBMT) by the European Society for Blood and Marrow Transplantation (EBMT), the Center for International Blood and Marrow Transplantation (CIBMTR), the Asian Pacific Blood and Marrow Transplant Group (APBMT), the Australia and New Zealand Transplant and Cellular Therapies Registry (ANZTCT), the Eastern Mediterranean Blood and Marrow Transplant Group (EMBMT), the Latin American Bone Marrow Transplant Group (LABMT), and the Ottawa Canadian Registry. There primary endpoints were overall (OS) and non-relapse mortality (NRM) and the secondary were progression free survival (PFS) and relapse incidence (RI). The Kaplan-Meier estimator and log-rank test were used for OS and PFS, and the crude cumulative incidence estimator and Gray's test were used for competing events (RI and NRM). Results: 61725 patients from 629 were included: 37549 (61%) from EBMT, 16217 (26%) CIBMTR), 3815 (6%) APBMT (3122 Japan, 524 Taiwan and 169 Malaysia), 3,164 (5%) ANZTCT, 543 (0.9%) EMBMT, 339 (0.5%) LABMT and 188 (0.3%) Ottawa). The annual number of ASCTs steadily increased between 2013 (n=11317) and 2017 (n=13498) with the biggest relative increase seen in LABMT (from 36 to 109). Males comprised 58% and the median age at diagnosis was 59.9 years (IQR: 53.6-64.9). Race data was available in 45%: 73% White, 16% Asian and 11% African American. The predominant phenotypes were IgG (54%), light chain (24%) (lowest (4%) in Malaysia and highest (38%) in EMBMT), and IgA (19%) (lowest (13%) in EMBMT and highest (24%) in Ottawa). The ISS stage at diagnosis (54% available) was I in 38%, II 35% and III 27% (III lowest (24%) in ANZTCT and highest (45%) in LABMT). Cytogenetic risk (44% available) was standard in 70% and high in 30% (high risk was lowest (5%) in EMBMT, and highest (62%) in Ottawa). The median time from diagnosis to ASCT was 7 months (IQR:5.5-9.9) (shortest (6.4) in CIBMTR and Ottawa, and longest (13) in LABMT). The median age at ASCT was 60.8 years (IQR: 54.6-65.8) (lowest (53.6) in EMBMT, and highest (62) in Ottawa). Only 5% of patients were older than 70 years (lowest (3.5%) in EBMT, and highest (9.8%) in CIBMTR). HCT-CI at ASCT (28% missing) was reported as low risk (0) in 52%, intermediate (1-2) 25% and high risk (≥3) 23% (high risk was lowest (5.5%) in LABMT and highest (42%) in CIBMTR). The Karnofsky score at ASCT (2.2 % missing) was 100 in 40% and ≤90 in 60% (≤90 was lowest (44%) in LABMT and highest (92%) in Ottawa). Disease status (9.7% missing) was CR in 19%, VGPR 38%, PR 36%, MR/SD 5% and refractory 2%. A ≥VGPR status at ASCT was 60% in EBMT, 55% CIBMTR, 39% ANZTCT, 51% Japan, 64% EMBMT, 71% Taiwan, 76% LABMT, 51% Ottawa and 54% Malaysia. The most frequent preparative regimen was melphalan 200 mg/m2 (82 %) (lowest (60%) in Malaysia and highest (90%) in Ottawa), 140 mg/m2 accounted for 14% and others for 4%. Tandem ASCT was reported in 6.7% (10% in EBMT, 1.3% in CIBMTR and 0.6% LABMT and Taiwan). The source of stem cells was peripheral blood in 99.8%. Of the 11% reported with post-ASCT maintenance treatment, 51% received lenalidomide. The median follow-up was 41.1 months (95% CI: 40.5-41.6, IQR:19.2-60.4). Regionally, at 3 years, the OS was : 81%, 84%, 82%, 83%, 77%, 75%, 84%, 82%, 69% (p<0.001), the PFS was 46%, 55%, 48%, 63%, 44%, 53%, 56%, 53%, 43% (p<0.001) (Figure) and the RI was:16%, 15%, 16%, 17%, 24%, 16%, 16%, 13%, 24% (p<0.001) for EBMT, CIBMTR, ANZTCT, Japan, EMBMT, Taiwan, LABMT, Ottawa and Malaysia, respectively. NRM at 1 year was between 1-2% in each registry (Figure). Conclusions: This large worldwide study of patients with NDMM treated with upfront ASCT revealed marked regional differences in transplant activity and patient characteristics. NRM was low worldwide but with differences in relapse incidence and survival potentially reflect variable health economic factors, including different access to new myeloma drugs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal
Authors 44
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Sorbonne Université · Pitié-Salpêtrière Hospital · Laboratoire d'hématologie
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1Service Hematologie, Sorbonne Université, Hopital Pitié Salpêtière APHP, Paris, France
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European Society for Blood and Marrow Transplantation
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2EBMT Statistical Unit, Leiden, The Netherlands, Leiden, Netherlands
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European Society for Blood and Marrow Transplantation
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3EBMT Data Office, Leiden, Netherlands
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4Department of medicine, medical college of Wisconsin, Milwaukee,
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5CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
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6Medical College of Wisconsin, Milwaukee, WI
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5CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
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7Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA
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8Aichi Medical University School of Medicine, Nagakute-cho, Aichi, JPN
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9Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
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10School of Entrepreneurial and Innovation Studies, Kanazawa University, Kanazawa, Japan
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Aichi Medical University · Aichi Medical University Hospital
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11Department of Hematology, Aichi Medical University School of Medicine, Nagakute, Japan
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Jichi Medical University Saitama Medical Center
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12Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan
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13Department of Promotion for Blood and Marrow Transplantation, Aichi Medical University School of Medicine, Nagoya, Japan
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UNSW Sydney · St Vincent's Hospital Sydney
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14Department of Haematology, St Vincent's Hospital Sydney, Australia and St Vincent's Clinical School, Sydney, University of New South Wales, Sydney, Australia
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National Taiwan University Hospital
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15National Taiwan University Hospital, Taipei, Taiwan
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16Hospital Ampang, Ampang, Selangor, Malaysia
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17Department of Hematology, Ampang Hospital, Ampang, Malaysia
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18Penang general hospital, Penang, Malaysia
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18Penang general hospital, Penang, Malaysia
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19Department of Pediatric Oncology and Stem Cell Transplantation Unit, National Cancer Institute, Cairo University, Cairo, Egypt
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American University of Beirut Medical Center · American University of Beirut
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20Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon
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21AFBMTC/NIBMT, Rawalpindi, Pakistan
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22King Hussein cancer center, Amman, Jordan
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Université Oran 1 Ahmed Ben Bella
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23Department of Hematology and Cell Therapy, EHU 1st Novembre 1954 Bir el Djir Usto, University Ahmed Benbella 1, Oran, Algeria
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24Centre Pierre et Marie Curie (CPMC), Algiers, Algeria
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25Hospital Central Del Instituto De Prevision Social, Asuncion, Paraguay
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26Cátedra de Hematología, Hospital de Clínicas, Facultad de Medicina, Montevideo, Montevideo, Uruguay
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27Hematology Department, British Hospital, Montevideo, Uruguay
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28Hospital del Salvador, Santiago, Chile
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29Department of Oncology, McMaster University, Hamilton, Canada
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30Department of Medicine, Division of Hematology, The Ottawa Hospital, Ottawa, Canada
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31Peking University, Beijing, China
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32IMISE, university of Leipzig, Leipzig, Germany
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St George's Hospital · St George’s University Hospitals NHS Foundation Trust
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33Department of Haematology, St George's Hospital NHS Foundation Trust, London, United Kingdom
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Sheffield Teaching Hospitals NHS Foundation Trust
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34BSBMTCT, Department of Haematology, Sheffield Teaching Hospitals NHS Trust, Sheffield, United Kingdom
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Heidelberg University · University Hospital Heidelberg
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35Department of Internal Medicine V, Amyloidosis Center, Heidelberg University Hospital, Heidelberg, Germany
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36Department of Haematology, Kings's College Hospital, London, United Kingdom
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Trinity College Dublin · St. James's Hospital
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37Department of Haematology, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland
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Institut d'Investigació Biomédica de Bellvitge · Institut Català d'Oncologia · Duran i Reynals Hospital · Universitat de Barcelona
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38Institut Català d'Oncologia, Hospital Duran i Reynals. Institut d'Investigació Biomèdica de Bellvitge (IDIBELL). Universitat de Barcelona, Barcelona, Spain
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39Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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King Faisal Specialist Hospital & Research Centre
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40Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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41Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan
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42University of Leipzig, Leipzig, Germany
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