Comparison of Outcomes after Haploidentical Relative and HLA Matched Unrelated Donor Transplantation with Post-Transplant Cyclophosphamide Containing Gvhd Prophylaxis Regimens
Authors: Gooptu Mahasweta , St. Martin Andrew , Romee Rizwan , Arora Mukta , Al Malki Monzr M. , Antin Joseph H. , Bredeson Christopher , Brunstein Claudio G. , Chhabra Saurabh , Fuchs Ephraim J. , Ghosh Nilanjan , Grunwald Michael R. , Inamoto Yoshihiro , Kanakry Christopher G. , Kekre Natasha , McGuirk Joseph P. , McNiece Ian K. , Mehta Rohtesh S. , Mielcarek Marco Last , Milano Filipo , Modi Dipenkumar , Reshef Ran , Schroeder Mark A. , Soiffer Robert J. , Solomon Scott R. , Waller Edmund K. , Eapen Mary 
Published: February 2021

Introduction: Post-transplant cyclophosphamide (PT-Cy) in HLA-haploidentical hematopoietic cell transplantation (Haplo-HCT) results in acceptable engraftment and graft-versus-host disease (GVHD). Results of BMT CTN 1203 that compared matched unrelated donor (MUD) HCT with PT-Cy containing to calcineurin inhibitor (CNI) containing GVHD prophylaxis following reduced intensity conditioning, showed better 1-year GVHD free relapse free survival with PT-Cy. The relative value of a MUD versus a Haplo donor in the context of PT-Cy is not known. In this study we compared outcomes after Haplo- and MUD HCT with PT-Cy containing GVHD prophylaxis.

Methods: Eligible patients were aged &gt;18 years and received haplo-HCT or MUD HCT for AML, ALL and MDS in the US from 2011-2018. Patients received myeloablative (n=1001) or reduced intensity (n=1398) regimens and were analyzed separately. All recipients of haplo-HCT and reduced intensity conditioning MUD HCT received PT-Cy + CNI + mycophenolate mofetil (MMF) for GVHD prophylaxis. Among recipients of myeloablative conditioning MUD HCT, 55% received PT-Cy + CNI + MMF and 45%, PT-Cy + CNI. Cox regression models were built to compare outcomes between donor types. As PT-Cy containing GVHD prophylaxis for myeloablative conditioning MUD HCT is recent; therefore, outcomes were censored at 1-year. A p-value ≤0.01 was considered significant.

Results: Myeloablative conditioning regimen: Age at transplant, sex, performance score, co-morbidity and CMV serostatus did not differ between recipients of haplo- and MUD HCT. Haplo-HCT recipients were less likely to be Caucasian (69% vs. 91%). They were also more likely to have AML (55% vs. 47) and less likely to have MDS (13% vs. 31%). Disease risk index did not differ between treatment groups. The predominant conditioning regimen for haplo-HCT was total body irradiation (TBI) + fludarabine (44%) for Haplo-HCT and for MUD HCT, fludarabine + busulfan ± thiotepa (59%). Engraftment rates did not differ between groups. Results of multivariate analyses are shown in Table 1. Compared to Haplo-HCT, grade II-IV acute GVHD risk was higher after MUD-HCT with PT-Cy + CNI GVHD prophylaxis. There were no differences in grade III-IV acute or chronic GVHD risk between treatment groups. Non-relapse mortality, relapse, disease-free and overall survival did not differ between treatment groups.

Reduced intensity conditioning regimen: Age at transplant, sex, performance score, co-morbidity and CMV serostatus did not differ between recipients of haplo- and MUD HCT. Haplo-HCT recipients were less likely to be Caucasian (72% vs. 95%). Haplo-HCT recipients were less likely to have MDS (19% vs. 24%). Disease risk index did not differ between treatment groups. The predominant conditioning regimen was TBI 200 cGy + fludarabine + cyclophosphamide (88%) for Haplo-HCT and for MUD HCT, TBI 200 cGy + fludarabine + cyclophosphamide (37%) and fludarabine + melphalan (33%). Engraftment rates did not differ between groups. Results of multivariate analyses are shown in Table 2. Compared to Haplo-HCT acute and chronic GVHD risks did not differ between treatment groups. However, non-relapse mortality was lower after MUD-HCT which led to higher disease-free and overall survival.

Conclusion: In patients who received myeloablative conditioning and PT-Cy + CNI + MMF GVHD prophylaxis, haploidentical related and matched unrelated donors are comparable. However, in patients who received less intense conditioning regimens, disease free and overall survival was higher after MUD HCT compared to Haplo-HCT.

Disclosures

Arora: Fate Therapeutics: Consultancy; Pharmacyclics: Research Funding; Kadmon: Research Funding; Syndax: Research Funding. Al Malki:Neximmune: Consultancy; Jazz Pharmacuticals, Inc: Consultancy; Rigel Pharma: Consultancy. Brunstein:Magenta: Research Funding; Gamida: Research Funding; Astex: Research Funding; AlloVir: Other: Advisory board. Grunwald:Merck: Consultancy; Agios: Consultancy; Abbvie: Consultancy; Agios: Consultancy; Celgene: Consultancy; Incyte: Consultancy, Research Funding; Premier: Consultancy; Amgen: Consultancy; Amgen: Consultancy; Merck: Consultancy; Cardinal Health: Consultancy; Celgene: Consultancy; Abbvie: Consultancy; Cardinal Health: Consultancy; Merck: Consultancy; Cardinal Health: Consultancy; Daiichi Sankyo: Consultancy; Agios: Consultancy; Abbvie: Consultancy; Incyte: Consultancy, Research Funding; Pfizer: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Premier: Consultancy; Trovagene: Consultancy; Astellas: Consultancy; Astellas: Consultancy; Premier: Consultancy; Trovagene: Consultancy; Trovagene: Consultancy; Genentech/Roche: Research Funding; Janssen: Research Funding; Genentech/Roche: Research Funding; Genentech/Roche: Research Funding; Forma Therapeutics: Research Funding; Merck: Research Funding; Janssen: Research Funding; Forma Therapeutics: Research Funding; Forma Therapeutics: Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Pfizer: Consultancy. Kekre:Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria. McGuirk:Juno Therapeutics: Consultancy, Honoraria, Research Funding; Allo Vir: Consultancy, Honoraria, Research Funding; Astellas: Research Funding; Fresenius Biotech: Research Funding; Novartis: Research Funding; Kite Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pluristem Ltd: Research Funding; Gamida Cell: Research Funding; Bellicum Pharmaceutical: Research Funding. Mehta:CSL Behring: Research Funding; Incyte: Research Funding; Kadmon: Research Funding. Modi:MorphoSys: Membership on an entity's Board of Directors or advisory committees. Reshef:Gilead: Consultancy, Honoraria, Other: Travel support, Research Funding; Immatics: Research Funding; Celgene: Consultancy; Takeda: Research Funding; Monsanto: Consultancy; Incyte: Research Funding; Shire: Research Funding; Novartis: Honoraria; Pharmacyclics: Research Funding; Magenta: Consultancy; Bristol-Myers Squibb: Research Funding; Kiadis: Research Funding; Bluebird: Research Funding; Atara: Consultancy, Research Funding. Schroeder:Partners Therapeutics: Other; Gilead Sciences Inc: Other; Pfizer: Other; Genentech Inc: Research Funding; Incyte Corporation: Other: served on advisory boards and received honoraria or consultant fees, Research Funding; Novo Nordisk: Other; Merck: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; GSK: Other; FlatIron Inc: Other; Dova Pharmaceuticals: Other; Astellas: Other; Janssen: Research Funding; Genzyme Sanofi: Other: served on advisory boards and received honoraria or consultant fees, Research Funding; PBD Incorporated: Research Funding; Celgene: Research Funding; Amgen: Other: served on advisory boards and received honoraria or consultant fees, Research Funding; Seattle Genetics: Research Funding; Fortis: Research Funding; Cellect Inc: Research Funding. Soiffer:alexion: Consultancy; Rheos Therapeutics: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; VOR Biopharma: Consultancy; Gilead: Consultancy; Be the Match/ National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Kiadis: Membership on an entity's Board of Directors or advisory committees; Precision Bioscience: Consultancy; Mana Therapeutics: Consultancy; Cugene: Consultancy; Juno: Membership on an entity's Board of Directors or advisory committees. Waller:Verastem Oncology, Inc: Consultancy, Research Funding.