Characteristics of Graft-Versus-Host Disease (GvHD) After Post-Transplantation Cyclophosphamide Versus Conventional GvHD Prophylaxis

Rima M. Saliba, Amin M. Alousi, Joseph Pidala, Mukta Arora, Stephen R Spellman, Michael T. Hemmer, Tao Wang, Camille Abboud, Sairah Ahmed, Joseph H. Antin, Amer Beitinjaneh, David Buchbinder, Michael Byrne, Jean Yves Cahn, Hannah Choe, Rabi Hanna, Peiman Hematti, Rammurti T. Kamble, Carrie L. Kitko, Mary LaughlinLazaros Lekakis, Margaret L. MacMillan, Rodrigo Martino, Parinda A. Mehta, Taiga Nishihori, Sagar S. Patel, Miguel Angel Perales, Hemalatha G. Rangarajan, Olov Ringdén, Joseph Rosenthal, Bipin N. Savani, Kirk R. Schultz, Sachiko Seo, Takanori Teshima, Marjolein van der Poel, Leo F. Verdonck, Daniel Weisdorf, Baldeep Wirk, Jean A. Yared, Jeffrey Schriber, Richard E. Champlin, Stefan O. Ciurea

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Post-transplantation cyclophosphamide (PTCy) has been shown to effectively control graft-versus-host disease (GvHD) in haploidentical (Haplo) transplantations. In this retrospective registry study, we compared GvHD organ distribution, severity, and outcomes in patients with GvHD occurring after Haplo transplantation with PTCy GvHD prophylaxis (Haplo/PTCy) versus HLA-matched unrelated donor transplantation with conventional prophylaxis (MUD/conventional). We evaluated 2 cohorts: patients with grade 2 to 4 acute GvHD (aGvHD) including 264 and 1163 recipients of Haplo and MUD transplants; and patients with any chronic GvHD (cGvHD) including 206 and 1018 recipients of Haplo and MUD transplants, respectively. In comparison with MUD/conventional transplantation ± antithymocyte globulin (ATG), grade 3-4 aGvHD (28% versus 39%, P = .001), stage 3-4 lower gastrointestinal (GI) tract aGvHD (14% versus 21%, P = .01), and chronic GI GvHD (21% versus 31%, P = .006) were less common after Haplo/PTCy transplantation. In patients with grade 2-4 aGvHD, cGvHD rate after Haplo/PTCY was also lower (hazard ratio [HR] =. 4, P < .001) in comparison with MUD/conventional transplantation without ATG in the nonmyeloablative conditioning setting. Irrespective of the use of ATG, non-relapse mortality rate was lower (HR =. 6, P = .01) after Haplo/PTCy transplantation, except for transplants that were from a female donor into a male recipient. In patients with cGvHD, irrespective of ATG use, Haplo/PTCy transplantation had lower non-relapse mortality rates (HR =. 6, P = .04). Mortality rate was higher (HR = 1.6, P = .03) during, but not after (HR =. 9, P =. 6) the first 6 months after cGvHD diagnosis. Our results suggest that PTCy-based GvHD prophylaxis mitigates the development of GI GvHD and may translate into lower GvHD-related non-relapse mortality rate.

Original languageEnglish (US)
Pages (from-to)681-693
Number of pages13
JournalTransplantation and Cellular Therapy
Volume28
Issue number10
DOIs
StatePublished - Oct 2022

Bibliographical note

Funding Information:
Conflict of interest statement: A.A.M. reports all support for the present manuscript including 8 hours of multiple proof, data assessment (noting discrepancy with respect to ATG), interpretation of data and suggested analysis. M.A. reports compensation from Fate Therapeutics and research funding from Pharmacyclics, Kadmon, and Syndax. M.T.H. reports honoraria for participating in an advisory board for Inotuzumab ozogamicin. T.W. reports support for the present manuscript including stem cell therapeutic outcomes database from HRSA, and a data resource for analyzing blood and marrow transplants from NIH/NCI. M.L.M. reports compensation for consultant for Talaris Therapeutics, Fate Therapeutics, Equillium Inc., and Incyte Corporation. T.N. reports research support to the institution for clinical trial by Novartis and Research support (drug supply only) to the institution for clinical trial by Karyopharm. M-A.P. reports personal fees from Abbvie, Bellicum, Bristol-Myers Squibb, Celgene, Cidara Therapeutics, Incyte, Kite/Gilead, Medigene, Miltenyi, MolMed, Nektar Therapeutics, NexImmune, Novartis, Omeros, Merck, Servier, Takeda, Karyopharm, Equilium, MorphoSys, VectivBio, and Vor Biopharma; other from Incyte, Kite/Gilead, Miltenyi, and Novartis, outside the submitted work. K.R.S. reports board participation BMS – on DSMC, MesoBlast – DSMC, PTCTC – DSMC, Board of directors CTTC and Scientific Steering committee with CureWorks. T.T. reports research funding, manuscript preparation, advisory board from Novartis, research funding from Chugai, research funding from Kyowa Kirin, research funding from Sanofi, research funding from Astellas, research funding from Teihin Pharma, research funding from Fuji Pharma, research funding from Nippon Shinyaku, honoraria from Merck Sharp & Dohme, honoraria from Takeda, honoraria from Kyowa Kirin, Bristol-Myers Squibb, honoraria from Pfizer, advisory board role of Merck Sharp & Dohme, advisory board role of Takeda, and manuscript preparation from Janssen. D.W. reports research support from Incyte and Fate Therapeutics, consulting fees from Endpoint adjudication consultation; FATE Therapeutics. Board and officer for WBMT. J.A.Y. reports one-time honoraria for one Ad Board meeting from Omeros. H.C. reports funding from Plexxikon (Clinical trial funding for IST, no direct research funds and receipt of drug for preclinical studies).

Funding Information:
Financial disclosure: 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, DBA Eurofins Transplant Diagnostics; Fate Therapeutics; Gamida-Cell, Ltd.; Gilead; GlaxoSmithKline; HistoGenetics; Incyte Corporation; Iovance; Janssen Research & Development, LLC; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Kadmon; Karius; Karyopharm Therapeutics; Kiadis Pharma; Kite Pharma Inc; Kite, a Gilead Company; Kyowa Kirin International plc; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Medac GmbH; Medexus; Merck & Co.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; OncoImmune, Inc.; Oncopeptides, Inc.; OptumHealth; Orca Biosystems, Inc.; Ossium Health, Inc; Pfizer, Inc.; Pharmacyclics, LLC; Priothera; Sanofi Genzyme; Seagen, Inc.; Stemcyte; Takeda Pharmaceuticals; Talaris Therapeutics; Terumo Blood and Cell Technologies; TG Therapeutics; Tscan; Vertex; Vor Biopharma; and Xenikos BV.

Funding Information:
Financial disclosure: 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, DBA Eurofins Transplant Diagnostics; Fate Therapeutics; Gamida-Cell, Ltd.; Gilead; GlaxoSmithKline; HistoGenetics; Incyte Corporation; Iovance; Janssen Research & Development, LLC; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Kadmon; Karius; Karyopharm Therapeutics; Kiadis Pharma; Kite Pharma Inc; Kite, a Gilead Company; Kyowa Kirin International plc; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Medac GmbH; Medexus; Merck & Co.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; OncoImmune, Inc.; Oncopeptides, Inc.; OptumHealth; Orca Biosystems, Inc.; Ossium Health, Inc; Pfizer, Inc.; Pharmacyclics, LLC; Priothera; Sanofi Genzyme; Seagen, Inc.; Stemcyte; Takeda Pharmaceuticals; Talaris Therapeutics; Terumo Blood and Cell Technologies; TG Therapeutics; Tscan; Vertex; Vor Biopharma; and Xenikos BV. Conflict of interest statement: A.A.M. reports all support for the present manuscript including 8 hours of multiple proof, data assessment (noting discrepancy with respect to ATG), interpretation of data and suggested analysis. M.A. reports compensation from Fate Therapeutics and research funding from Pharmacyclics, Kadmon, and Syndax. M.T.H. reports honoraria for participating in an advisory board for Inotuzumab ozogamicin. T.W. reports support for the present manuscript including stem cell therapeutic outcomes database from HRSA, and a data resource for analyzing blood and marrow transplants from NIH/NCI. M.L.M. reports compensation for consultant for Talaris Therapeutics, Fate Therapeutics, Equillium Inc. and Incyte Corporation. T.N. reports research support to the institution for clinical trial by Novartis and Research support (drug supply only) to the institution for clinical trial by Karyopharm. M-A.P. reports personal fees from Abbvie, Bellicum, Bristol-Myers Squibb, Celgene, Cidara Therapeutics, Incyte, Kite/Gilead, Medigene, Miltenyi, MolMed, Nektar Therapeutics, NexImmune, Novartis, Omeros, Merck, Servier, Takeda, Karyopharm, Equilium, MorphoSys, VectivBio, and Vor Biopharma; other from Incyte, Kite/Gilead, Miltenyi, and Novartis, outside the submitted work. K.R.S. reports board participation BMS – on DSMC, MesoBlast – DSMC, PTCTC – DSMC, Board of directors CTTC and Scientific Steering committee with CureWorks. T.T. reports research funding, manuscript preparation, advisory board from Novartis, research funding from Chugai, research funding from Kyowa Kirin, research funding from Sanofi, research funding from Astellas, research funding from Teihin Pharma, research funding from Fuji Pharma, research funding from Nippon Shinyaku, honoraria from Merck Sharp & Dohme, honoraria from Takeda, honoraria from Kyowa Kirin, Bristol-Myers Squibb, honoraria from Pfizer, advisory board role of Merck Sharp & Dohme, advisory board role of Takeda, and manuscript preparation from Janssen. D.W. reports research support from Incyte and Fate Therapeutics, consulting fees from Endpoint adjudication consultation; FATE Therapeutics. Board and officer for WBMT. J.A.Y. reports one-time honoraria for one Ad Board meeting from Omeros. H.C. reports funding from Plexxikon (Clinical trial funding for IST, no direct research funds and receipt of drug for preclinical studies). Financial disclosure: See Acknowledgments on page 692.

Publisher Copyright:
© 2022 The American Society for Transplantation and Cellular Therapy

Keywords

  • Graft-versus-host disease
  • Non-relapse mortality
  • Post-transplantation cyclophosphamide
  • Prophylaxis

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

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