Haploidentical Vs. Matched Unrelated Donor Transplants Using Post-Transplant Cyclophosphamide for Lymphoma: A Joint CIBMTR/EBMT Study

Mussetti, Alberto

Oral and Poster Abstracts
Oral
732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Novel Approaches and Outcomes

Clinical Research, Clinically Relevant

Alberto Mussetti¹^*, Abraham S. Kanate, MD², Tao Wang, PhD^3,4^*, Meilun He, MPH⁵^*, Mehdi Hamadani, MD⁶, Hervé Finel Sr., MD, PhD⁷^*, Ariane Boumendil Sr., PhD⁷^*, Bertram Glass, MD⁷^*, Luca Castagna⁸^*, Didier Blaise⁹, Steven G.E. Marsh, BSc, PhD, ARCS^10,11^*, Sophie Paczesny, MD, PhD¹², Shahinaz M. Gadalla, MD, PhD¹³, Peter Dreger, MD¹⁴, Stephen R. Spellman, MBS⁵^*, Stephanie J. Lee^15,16^*, Yung-Tsi Bolon, PhD¹⁷^* and Anna Sureda¹⁸

¹IDIBELL-Institut Català d'Oncologia, l'Hospitalet de Llobregat, El Prat de Llobregat, Spain
²Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University, Morgantown, WV
³Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI
⁴Division of Biostatistics, Institute for Health and Equity,, Medical College of Wisconsin, Milwaukee, WI
⁵CIBMTR® (Center for International Blood and Marrow Transplant Research), National Marrow Donor Program/Be The Match, Minneapolis, MN
⁶BMT & Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
⁷Lymphoma Working Party, EBMT Central Registry Office, Paris, France
⁸IRCCS Humanitas Research Hospital, Rozzano, Milano, Italy
⁹Department of Hematology, Institut Paoli Calmettes, Marseille, France
¹⁰University College London Cancer Institute, University College London, London, United Kingdom
¹¹Anthony Nolan Research Institute, London, United Kingdom
¹²Department of Microbiology and Immunology, Medical University of South Carolina College of Medicine, Charleston
¹³Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
¹⁴Medizinische Klinik V Studienzentrale, Universitaetsklinikum Heidelberg, Heidelberg, Germany
¹⁵Fred Hutchinson Cancer Research Center, Seattle
¹⁶CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI
¹⁷CIBMTR® (Center for International Blood and Marrow Transplant Research), National Marrow Donor Program /Be The Match, Minneapolis, MN
¹⁸Hematology Department, Institut Català d'Oncologia - Hospitalet, IDIBELL, University of Barcelona, Barcelona, Spain

Introduction: Post-transplant cyclophosphamide (PTCy) is a standard GVHD prophylactic approach for haploidentical hematopoietic cell transplantation (haploHCT). Retrospective studies in patients with lymphoma showed lower chronic GVHD in haploHCT with PTCy-based GVHD prophylaxis compared to matched unrelated donor (MUD) HCT with calcineurin-based GVHD prophylaxis (+/- ATG). Recent retrospective studies showed that using MUD donors was better than haplo donors when PTCy and reduced-intensity conditioning are used for ALL, AML or MDS. However, no studies to date have compared haploHCT and MUD HCT when PTCy is used in the setting of lymphomas.

Methods: 2155 adults (730 CIBMTR, 1425 EBMT) aged =/>18 years who received their first haploHCT or MUD HCT (8/8 match at HLA-loci A, B, C and DRB1) using PTCy from 2010-2019 for lymphoma were included. The majority of both MUD (n=312; 14%) and haplo (n=1843; 86%) HCTs received reduced intensity/non-myeloablative conditioning (n=1655; 77%) using a peripheral blood stem cell graft (n=1379; 64%) and a three-drug GVHD prophylaxis (PTCy + calcineurin inhibitor + MMF, n=1805; 84%). Hodgkin’s lymphoma was the most common indication (n=899; 42%) followed by diffuse large B-cell lymphoma (n=525; 24%), T-cell lymphomas (n=328; 15%), mantle cell lymphoma (n=234; 11%) and follicular lymphoma (n=169; 8%). Most had chemosensitive disease at transplant (n=1781; 83%). Some main characteristics of the two cohorts are shown in Figure 1. Median follow-up among survivors was longer for haplo-HCT (36 and 31 months for the CIBMTR and EBMT cohort, respectively) than MUD-HCT (24 and 17 months, respectively). Cox proportional hazards models were built using stepwise forward and backward selection with a selection/retention threshold of 0.05. Any clinical variables that did not meet the proportional hazard assumption were adjusted for by stratification, and regression models were built to compare outcomes between donor types. Center effect was adjusted in all the models.

Results: Figures 2 and 3 show the multivariate analysis results. Overall survival was 73% (71-75%) at 1 year and 65% (63-67%) at 2 years. Relapse was 21% (20-23%) at 1 year and 26% (24-28%) at 2 years. All outcomes favored MUD over haplo donors with the use of PTCy-based GVHD prophylaxis for both.

Conclusions: Patients with lymphoma receiving PTCy HCT from MUDs demonstrated better outcomes than those with haplo donors in this retrospective study of CIBMTR and EBMT data Future prospective studies are needed to confirm and clarify the reasons for these differences.

Disclosures: Mussetti: GILEAD: Other: Clinical trials participation, Research Funding; TAKEDA: Honoraria; NOVARTIS: Honoraria, Other: Clinical trials participation. Hamadani: Sanofi, Genzyme, AstraZeneca, BeiGene: Speakers Bureau; Janssen, Incyte, ADC Therapeutics, Omeros, Morphosys, Kite: Consultancy; Takeda, Spectrum Pharmaceuticals and Astellas Pharma: Research Funding. Glass: Novartis: Consultancy; Riemser: Research Funding; Helios Klinik Berlin-Buch: Current Employment; Kite: Consultancy; Roche: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy. Blaise: Jazz Pharmaceuticals: Honoraria. Paczesny: Medical University of South Carolina: Patents & Royalties: inventor on the ST2 bispecific antibody patent application. Dreger: Novartis: Consultancy, Speakers Bureau; Riemser: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy; Bluebird Bio: Consultancy; AstraZeneca: Consultancy, Speakers Bureau; Gilead Sciences: Consultancy, Speakers Bureau; Janssen: Consultancy; AbbVie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau. Lee: AstraZeneca: Research Funding; Incyte: Research Funding; Janssen: Other; Kadmon: Research Funding; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Syndax: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Amgen: Research Funding. Sureda: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Mundipharma: Consultancy; Bluebird: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Support for attending meetings and/or travel; GSK: Consultancy, Honoraria, Speakers Bureau.

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174 Haploidentical Vs. Matched Unrelated Donor Transplants Using Post-Transplant Cyclophosphamide for Lymphoma: A Joint CIBMTR/EBMT Study