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4895 Separation of Gvl Effects from GvHD with Ptcy-Based Gvhd Prophylaxis in Mmud Transplantation: A Study from the ALWP of the EBMT

Program: Oral and Poster Abstracts
Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD and Immune Reconstitution: Poster III
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Practice (Health Services and Quality), Clinical Research, Registries
Monday, December 9, 2024, 6:00 PM-8:00 PM

Frederic Baron1, Allain Thibeault Ferhat Berland2*, Myriam Labopin3*, Matthias Eder, MD4*, Alessandro Rambaldi5, Cristina Castilla-Llorente, MD6*, Igor Wolfgang Blau, MD, PhD7*, Francesca Bonifazi8*, Thomas Schroeder9*, Nicolaus Kröger, MD10*, Didier Blaise, MD11*, Peter Dreger12, Tobias Gedde-Dahl13*, Jaime Sanz14*, Mohamad Mohty, MD, PhD15 and Fabio Ciceri, MD16*

1University of Liege, Liege, Belgium
2EBMT Paris study office, Paris, France
3EBMT Statistical Unit, Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France
4Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
5Department of Oncology-Hematology, Azienda Socio-Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy
6Gustave Roussy Cancer Campus, Villejuif, France
7Medizinische Klinik m. S. Hämatologie , Onkologie und Tumorimmunologie, Berlin, Germany, Berlin, Germany
8Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology "Seràgnoli" University of Bologna, Bologna, Italy
9Dept. of Hematology and Stem Cell Transplantation West German Cancer Centre University Hospital Essen Essen, Germany, Essen, Germany
10German Registry for Hematopoietic Stem Cell Transplantation and Cell Therapy (DRST), Ulm, Germany
11Programme de Transplantation & Thérapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Marseille, France
12Department of Medicine V, Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany
13Rikshospitalet, Oslo University Hospital, Oslo, Norway
14Hematology Department, Hospital Universitari i Politècnic La Fe, Departament de Medicina Universitat de Valencia, CIBERONC, Instituto Carlos III, Spain, VALENCIA, Spain
15Sorbonne University, Hôpital Saint-Antoine, and INSERM UMRs938, Paris, France
16Hematology and Bone Marrow Transplantation Unit, I.R.C.C.S. San Raffaele Scientific Institute, Milan, Italy

Background: The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HCT) in patients with acute myeloid leukemia (AML) depends on immune-mediated graft-versus-leukemia (GvL) effects. GvL effects have been closely linked to graft-versus-host disease (GVHD), and many studies have observed a significant association between GVHD occurrence and lower incidence of AML relapse after allo-HCT1,2. However, recent studies in patients receiving grafts from HLA-haploidentical donors with post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis failed to observe such an association3,4, suggesting that PTCy might separate GvL effects from GVHD. In order to determine whether the separation of GvL effects from GVHD observed in PTCy-based HLA-haploidentical transplantation is indeed due to PTCy, we compared the impact of GVHD occurrence on AML relapse in a large cohort of AML patients receiving peripheral blood stem cells (PBSC) from 9/10 HLA-mismatched unrelated donor (UD 9/10) and either antithymocyte-globulin (ATG)-based or PTCy-based GVHD prophylaxis. Methods: Inclusion criteria consisted of adult AML patients, PBSC from UD 9/10, PTCy-based or ATG-based GVHD prophylaxis (no combination or alemtuzumab), first allo-HSCT between 2015 and 2022, and no ex vivo T-cell depletion. The impact of GVHD on transplantation outcomes was assessed using multivariate Cox models in which grade II-IV acute and chronic GVHD were handled as time-dependent variables. Results: Data from a total of 1989 patients given ATG-based (n=1560) or PTCy-based (n=429) GVHD prophylaxis were included. Two-year relapse incidence was 29.5% (95% CI: 27.1-31.9%) in ATG patients versus 26.8% (95% CI: 22.2-31.6%) in PTCy patients (P=0.25 in multivariate analysis (MVA)). Two-year non-relapse mortality (NRM) and leukemia-free survival (LFS) were 23.2% (95%CI: 21-25.4%) and 47.3% (95% CI: 44.7-49.9%) in ATG patients versus 11.8% (95%CI: 8.7-15.3%) and 61.4% (95% CI: 56.1-66.4%) in PTCy patients (P<0.001 and P<0.001 respectively, in MVA). The incidences of grade II-IV acute at day 180 (30% versus 29%) and of chronic GVHD at 2 years (30% versus 30%) were comparable in ATG and PTCy patients. Among the former, occurrence of grade II-IV acute GVHD was associated with a lower risk of AML relapse (HR=0.79, P=0.028), higher NRM (HR=1.41, P=0.002) and comparable LFS (HR=1.05, P=0.5) confirming an association between GVHD and GvL effects in that setting. In contrast, chronic GVHD was not associated with a lower relapse incidence (HR=1.43, P=0.06) but was strongly associated with NRM (HR=3.16, P<0.001) leading to worse LFS (HR=2.24, P<0.001). Among PTCy patients, neither grade II-IV acute GVHD (HR=0.9, P=0.68) nor chronic GVHD (HR=0.58, P=0.37) were associated with relapse incidence. Chronic GVHD, however, correlated with higher NRM (HR=5.0, P<0.001) but comparable LFS (HR=1.53, P=0.22). Conclusions: This study is in line with the hypothesis of a separation of GvL effects from GVHD by the use of PTCy-based GVHD prophylaxis. In contrast, among ATG patients, grade II-IV acute GVHD occurrence was associated with a lower risk of relapse. Finally, this large study demonstrated, with the limitation of a retrospective analysis, better outcomes with PTCy-based than with ATG-based GVHD prophylaxis in patients given PBSC from UD 9/10.

References:

  1. Baron, F. et al. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation. Leukemia 26, 2462–2468 (2012).
  2. Gyurkocza, B. et al. Nonmyeloablative allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 28, 2859–2867 (2010).
  3. Shimoni, A. et al. The association of graft-versus-leukemia effect and graft-versus host disease in haploidentical transplantation with post-transplant cyclophosphamide for AML. Bone Marrow Transplant. 57, 384–390 (2022).
  4. Baron, F. et al. GVHD occurrence does not reduce AML relapse following PTCy-based haploidentical transplantation: a study from the ALWP of the EBMT. J. Hematol. Oncol. 16, 10 (2023).

Disclosures: Rambaldi: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Kite-Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau; Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Speakers Bureau. Bonifazi: MSD: Honoraria, Speakers Bureau; SANOFI: Honoraria; PFIZER: Honoraria, Speakers Bureau; NEOVII: Honoraria; JANSSEN: Honoraria, Speakers Bureau; JAZZ PHARMACEUTICALS: Honoraria, Speakers Bureau; KITE: Honoraria, Speakers Bureau; AMGEN: Honoraria, Speakers Bureau; bms: Honoraria, Speakers Bureau; TAKEDA: Honoraria, Speakers Bureau. Kröger: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Neovii: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees; Therakos: Honoraria, Speakers Bureau; Alexion: Honoraria, Speakers Bureau; Kite/Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; DKMS: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Provirex: Consultancy. Mohty: Takeda: Honoraria; GSK: Honoraria; Adaptive: Honoraria; Stemline Menarini: Honoraria; BMS: Consultancy, Honoraria; Novartis: Honoraria; Amgen: Honoraria; Pfizer: Consultancy, Current holder of stock options in a privately-held company, Honoraria, Research Funding, Speakers Bureau; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; MaaT Pharma: Current equity holder in publicly-traded company. Ciceri: ExCellThera: Membership on an entity's Board of Directors or advisory committees.

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