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Maintenance therapy after second autologous hematopoietic cell transplantation for multiple myeloma. A CIBMTR analysis

Abstract

The role of maintenance therapy after high-dose chemotherapy and first autologous transplantation in multiple myeloma (MM) is well established. We explored the effect of maintenance therapy on outcomes after salvage second autologous hematopoietic cell transplant (AHCT2) using the Center for International Blood and Marrow Transplant Research registry. Outcomes of interest included non-relapse mortality (NRM), relapse/progression (REL), progression-free and overall survival (PFS, OS). Of 522 patients who underwent AHCT2 between 2010 and 2018, 342 received maintenance therapy and 180 did not. Maintenance regimens included lenalidomide (42%), pomalidomide (13%), and bortezomib (13%). Median follow up was 58 months in the maintenance group and 61.5 months in the no-maintenance group. Univariate analysis showed superior outcomes at 5 years in maintenance compared to the no-maintenance group: NRM 2 (0.7–3.9)% vs 9.9 (5.9–14.9)%, (p < 0.01), REL 70.2 (64.4–75.8)% vs 80.3 (73.6–86.3)% (p < 0.01), PFS 27.8 (22.4–33.5)% vs. 9.8 (5.5–15.2)% (p < 0.01), and OS 54 (47.5–60.5)% vs 30.9 (23.2–39.2)% (p < 0.01), respectively. Use of maintenance therapy retained its association with improved outcomes in multivariate analysis. There was no difference in second cancers in the two groups (p = 0.39). We conclude that maintenance after AHCT2 is associated with improved 5-year outcomes.

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Fig. 1: Post-transplant outcomes.

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CIBMTR supports accessibility of research in accord with the National Institutes of Health (NIH) Data Sharing Policy and the National Cancer Institute (NCI) Cancer Moonshot Public Access and Data Sharing Policy. The CIBMTR only releases de-identified datasets that comply with all relevant global regulations regarding privacy and confidentiality.

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Acknowledgements

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); HHSH250201700006C from the Health Resources and Services Administration (HRSA); and N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research; Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and from the following commercial entities: AbbVie; Accenture; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; Adienne SA; Allovir, Inc.; Amgen, Inc.; Astellas Pharma US; bluebird bio, inc.; Bristol Myers Squibb Co.; CareDx; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Eurofins Viracor; ExcellThera; Fate Therapeutics; Gamida-Cell, Ltd.; Genentech Inc; Gilead; GlaxoSmithKline; Incyte Corporation; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karyopharm Therapeutics; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Magenta Therapeutics; Medac GmbH; Merck & Co.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncopeptides, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Seagen, Inc.; Stemcyte; Takeda Pharmaceuticals; Tscan; Vertex; Vor Biopharma; Xenikos BV. Anita D’Souza is supported by K23 HL141445 grant from the NHLBI.

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Authors and Affiliations

Authors

Contributions

Protocol development—OP, MY, AD. Reviewed protocol: MY, UR, LS, AA, RB, NB, RG, PH, LH, NH, HL, CL, HM, KM, SN, AN, TN, RP, SP, MS, SU, TW, BW, NE, RF, SK, NS, MQ. Data cleanup: NE, AD Data analysis: NE, RF, AD. Results review: OP, NE, RF, SK, NS, MQ, AD. Wrote the first draft: OP, AD Reviewed and edited paper: MY, UR, LS, AA, RB, NB, RG, PH, LH, NH, HL, CL, HM, KM, SN, AN, TN, RP, SP, MS, SU, TW, BW, NE, RF, SK, NS, MQ. All authors approved the final submitted draft.

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Correspondence to Anita D’Souza.

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Competing interests

Anita D’Souza reports institutional research funding from Sanofi, TeneoBio and Takeda; Consulting fees from Janssen; 2/2020-current. Rahul Banerjee reports grants or contracts from Pack Health to institution; consulting fees from SparkCures to self; and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid to ASTCT Content Committee. Robert Peter Gale reports consulting fees with Kite Pharms, Inc., Fusion Pharma, LLC, C Stone Pharmaceuticals; and stock or stock options with Celgene Corporation. Leona Holmberg reports grants to self from Seattle Genetics, Sanofi, Millennium-Takada, Bristol Myers Squibb, Merck, Janssen; and royalties to Up-To-Date. Hillard M. Lazarus reports participation on a Data Safety Monitoring Board or Advisory Board with Bristol Myers Squibb/Celgene DSMB for CAR-T cell therapy in myeloma. Taiga Nishihori reports clinical trial support by Novartis to the institution; and drug supply by Karyopharm to the institution. Mark A. Schroeder reports consulting fees with Equillium Inc 2021; served on the speakers bureau and received honorary as a consultant for this work from Abbvie (May 2019), Merck (May 2019), Takeda (May 2019) and all speakers bureau service terminated in August 2019; and served on advisory boards and received honorary or consultant fees from Amgen (2017), Dova pharmaceuticals (May 2019), Dova pharmaceuticals (May 2019), FlatIron Inc (June 2019), GSK (October 2019), Gilead Sciences Inc., (~2017), Incyte (May 2018), Janssen (December 2020), Novo Nordisk (2018), Partner Therapeutics (November 2018), Pfizer (July 2018), and Sanofi Genzyme (December 2020). Saad Z. Usmani reports grants and/or personal fees from Amgen, Abbvie, BMS, Celgene, MundiPharma, Pharmacyclics, Sanofi, Seattle Genetics, Janssen, Takeda, SkylineDX, grants Merck, GSK, outside the submitted work. Shaji Kumar reports research support for clinical trials paid to institution form Abbvie, Celgene, Janssen, Takeda, Adaptive, KITE, Medimmune/Astra Zeneca, Merck, Novartis, Roche, Sanofi; research support for clincal trials paid to institution for past 36 months from Abbvie, Celgene, Janseen, Takeda, Adaptive, KITE, Medimmune/Astra Zeneca, Merck, Novartis, Roche and Sanofi; advisory board participation, paid to institution from Abbvie, Celgene, Janssen, Takeda, Adaptive, KITE, Medimmune/Astra Zeneca; and independent review committee from Oncopeptides. Muzaffar H. Qazilbash reports participation on advisory board from Oncopeptides and data safety monitoring board for Autolus. Nina Shah reports compensation for research funding from Celgene/BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar; Advisory role for GSK, Amgen, Indapta Therapeutics, Sanofi, CareDx, Kite, Karyopharm, Oncopeptides; and payments for research funding from Celgene/BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar.

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Pasvolsky, O., Yeshurun, M., Fraser, R. et al. Maintenance therapy after second autologous hematopoietic cell transplantation for multiple myeloma. A CIBMTR analysis. Bone Marrow Transplant 57, 31–37 (2022). https://doi.org/10.1038/s41409-021-01455-y

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