Abstract
We studied 2,528 patients with upfront autologous haematopoietic cell transplantation (AHCT) for multiple myeloma (MM) from 2008–2017 to develop a prognostic model to predict outcomes. High-risk cytogenetics included t(4;14), t(14;16), t(14;20), del13q on karyotype, del17p, +1q or 1pdel. A Cox model identified factors prognostic of progression/relapse in a training subset (n = 1,246). A weighted score using these factors was assigned to a validation cohort (n = 774). Presence of high-risk cytogenetics [hazard ratio, (HR) 1·68 (1·3–2·17)] and pre-AHCT bone marrow plasma cells (BMPCs) ≥10% [1·68 (1·33–2·12)] were assigned 4 points each; albumin at diagnosis <3·5 g/dl [1·31 (1·07–1·61)] 2; standard risk cytogenetics 1, and no cytogenetics abnormality, BMPCs <10% at AHCT and albumin ≥3·5 g/dl at diagnosis 0 points each. A three-category system with low risk (0–3), intermediate risk (4–8) and high risk (9–10) showed 3-year progression-free survival in the low vs. intermediate vs. high risk of 58% (95% CI: 52–63) vs. 49% (95% CI: 43–56) vs. 31% (95% CI: 12–51), P < 0.001 respectively, and 3-year OS in low vs. intermediate vs. high risk of 88% (95% CI: 84–91) vs. 81% (95% CI: 76–86) vs. 64% (95% CI: 39–80); P < 0·001. Our prognostic scoring system can identify MM patients at risk for early relapse after AHCT.
| Original language | English |
|---|---|
| Pages (from-to) | 442-452 |
| Number of pages | 11 |
| Journal | British Journal of Haematology |
| Volume | 191 |
| Issue number | 3 |
| DOIs | |
| State | Published - Nov 1 2020 |
Bibliographical note
Publisher Copyright:© 2020 British Society for Haematology and John Wiley & Sons Ltd
Funding
The CIBMTR is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); U24HL138660 from NHLBI and NCI; OT3HL147741, R21HL140314 and U01HL128568 from the NHLBI; HHSH250201700006C, SC1MC31881‐01‐00 and HHSH250201700007C from the Health Resources and Services Administration (HRSA); and N00014‐18‐1‐2850, N00014‐18‐1‐2888, and N00014‐20‐1‐2705 from the Office of Naval Research; Additional federal support is provided by P01CA111412, R01CA152108, R01CA215134, R01CA218285, R01CA231141, R01HL126589, R01AI128775, R01HL129472, R01HL130388, R01HL131731, U01AI069197, U01AI126612, and BARDA. Support is also provided by Be the Match Foundation, Boston Children’s Hospital, Dana Farber, Japan Hematopoietic Cell Transplantation Data Center, St. Baldrick’s Foundation, the National Marrow Donor Program, the Medical College of Wisconsin and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies; Adienne SA; Allovir, Inc.; Amgen, Inc.; Anthem, Inc.; Astellas Pharma US; AstraZeneca; Atara Biotherapeutics, Inc.; bluebird bio, Inc.; Bristol Myers Squibb Co.; Celgene Corp.; Chimerix, Inc.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Gamida‐Cell, Ltd.; Genzyme; GlaxoSmithKline (GSK); HistoGenetics, Inc.; Incyte Corporation; Janssen Biotech, Inc.; Janssen Pharmaceuticals, Inc.; Janssen/Johnson & Johnson; Jazz Pharmaceuticals, Inc.; Kiadis Pharma; Kite Pharma; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Mallinckrodt LLC; Medac GmbH; Merck & Company, Inc.; Merck Sharp & Dohme Corp.; Mesoblast; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; Novartis Oncology; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Regeneron Pharmaceuticals, Inc.; REGiMMUNE Corp.; Sanofi Genzyme; Seattle Genetics; Sobi, Inc.; Takeda Oncology; Takeda Pharma; Terumo BCT; Viracor Eurofins and Xenikos BV. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. CIBMTR supports accessibility of research in accord with the National Institutes of Health (NIH) Data Sharing Policy and the National Cancer Institute Cancer Moonshot Public Access and Data Sharing Policy. The CIBMTR releases only de‐identified data sets that comply with all relevant global regulations regarding privacy and confidentiality. B.D. has served on the advisory board of Takeda, Amgen and Jansen and has received honorarium from Celgene; A.D’S. has received research funding from Takeda, Sanofi, TeneoBio and Mundipharma EDO and has consulted for Pfizer, Akcea, and Imbrium Therapeutics; M.AK‐D. reports other from Daiichi Sankyo and Pharmacyclics, outside the submitted work; N.S. received research funding, from Celgene, Janssen, Bluebird Bio Sutro Biopharma and Teneobio, N.S. has also acted in an advisory role for Genentech, Seattle Genetics, Oncopeptides, Karyopharm, Surface Oncology, Precision Biosciences GSK, Nektar, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx. Stock ownership and Indapta Therapeutics; A.A. reports grants from Incyte Corporation and personal fees from Incyte Corporation and Tolero Pharmaceuticals and grants from Regimmune, outside the submitted work; K.A. reports personal fees from Celgene, Janssen, Sanofi Aventis, Gilead, Millennium‐Takeda and Bristol Myers Squibb, outside of the submitted work; S.G. reports personal fees from Seattle Genetics, Kite Pharma and Kadmon, outside the submitted work; A.K. reports other from Takeda, Jansen, Pfizer, Karyopharm, Celgene/BMS and Sanofi, outside the submitted work; J.B. reports grants from Abbvie, Amgen, Acetylon, BioClinica, Bluebird, BMS, Celgene, Cellularity, Constellation, CRISPR, CURIS, EMD Sorono, Genentech, Glenmark, Janssen, Karyopharm, Kesios, Kite Pharma, Legend, Lilly, Novartis, Poseida, Prothena, Sanofi, Secura Bio, Sevier, Takeda, Teva, and Vivolux, outside the submitted work; S.K. reports grants and other from Abbvie, Celgene, Janssen, Takeda, Adaptive, KITE, Medimmune/Astra Zeneca, Oncopeptides and grants from Merck, Novartis, Roche and Sanofi, outside the submitted work; M.Q. reports other from Jenssen, Bioline, Angiocrine and Bioclinica, outside the submitted work; J.C. reports personal fees from Incyte Inc, Jazz Pharmaceuticals Inc., Daiichi‐Sankyo Inc., Pfizer Inc., outside the submitted work and owns stocks in Bluebird Bio Inc.
| Funders | Funder number |
|---|---|
| CytoSen Therapeutics, Inc. | |
| Daiichi Sankyo Company, Limited | |
| Daiichi‐Sankyo Inc. | |
| Dana-Farber Cancer Institute | |
| HistoGenetics, Inc. | |
| Janssen/Johnson & Johnson | |
| Magenta Therapeutics | |
| Mallinckrodt LLC | |
| Match Foundation | |
| TeneoBio | |
| Office of Naval Research Naval Academy | R01AI128775, U01AI069197, R01HL129472, U01AI126612, R01HL130388, R01HL131731, R01HL126589 |
| National Heart, Lung, and Blood Institute (NHLBI) | U24HL138660, U01HL128568, R21HL140314 |
| National Childhood Cancer Registry – National Cancer Institute | P01CA111412, R01CA231141, R01CA218285, U24CA076518, R01CA215134, R01CA152108 |
| National Institute of Allergy and Infectious Diseases | OT3HL147741, HHSH250201700006C, SC1MC31881‐01‐00 |
| Health Resources and Services Administration | N00014‐20‐1‐2705, N00014‐18‐1‐2850, N00014‐18‐1‐2888 |
| Intel Corporation | |
| AMGen | |
| Pfizer | |
| Merck | |
| Novartis | |
| Sanofi | |
| Gilead Sciences | |
| Janssen Biotech | |
| Teva Pharmaceutical Industries Ltd. | |
| Celgene | |
| AbbVie | |
| Children's Hospital Boston | |
| U.S. Public Health Service | |
| Takeda Pharmaceuticals U.S.A. | |
| CSL Behring GmbH | |
| Janssen Pharmaceuticals | |
| Medical College of Wisconsin | |
| Biomedical Advanced Research and Development Authority | |
| CareDx Incorporated | |
| Mundipharma EDO | |
| Chimerix Incorporated |
Keywords
- AHCT
- MM
- prognostic scoring system
ASJC Scopus subject areas
- Hematology