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4894 Decreased Chronic GvHD with Post-Transplant Cyclophosphamide (PTCY) Compared to ATG in Patients with Myelofibrosis Allografted with Unrelated Donor: A Study from the Chronic Malignancies Working Party 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, MPN, Clinical Research, Chronic Myeloid Malignancies, Diseases, Treatment Considerations, Biological therapies, Registries, Myeloid Malignancies, Transplantation (Allogeneic and Autologous)
Monday, December 9, 2024, 6:00 PM-8:00 PM

Yves Chalandon1, Edouard F. Bonneville2*, Liesbeth C. de Wreede2*, Linda Koster3*, Joe Tuffnell3*, Jakob Passweg, MD4*, Johannes Schetelig, MD, MSc5, Uwe Platzbecker, MD6,7, Ibrahim Yakoub-Agha, MD, PhD8*, Urpu Salmenniemi, MD9*, Mareike Verbeek, MD10*, Moniek De Witte, MD11*, Jean-Baptiste Méar, MD12*, John Snowden, MD13*, Tobias A.W. Holderried, MD14,15*, Gwendolyn Van Gorkom, MD16*, Frederic Baron17, Marie Robin, MD18*, Xavier Poiré, MD, PhD19*, Mieke Roeven, MD20*, Maija Itälä-Remes, MD, PhD21*, Jan Maciej Zaucha22*, Kavita K Raj, MD, PhD, FRCP, FRCPath23, Joanna Drozd-Sokolowska, MD, PhD24*, Giorgia Battipaglia, MD25*, Nicola Polverelli26, Tomasz Czerw, MD27*, Juan Carlos Hernandez Boluda, MD, PhD28* and Donal P McLornan, MD, PhD29*

1Hematology Service and Faculty of Medicine, University Hospital of Geneva, Geneva, Switzerland
2Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands
3EBMT Leiden Study Unit, Leiden, Netherlands
4University Hospital Basel, Basel, Switzerland
5Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Saxony, Germany
6Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany
7Department for Hematology, Cell Therapy, Hemostaseology and Infectious Diseases, University of Leipzig Medical Center, Leipzig, Germany
8CHU de Lille, Université de Lille, INSERM U1286, Infinite, 59000, Lille, France
9HUCH Comprehensive Cancer Center, Helsinki, Finland, Helsinki, Finland
10Department of Medicine III, Hematology and Oncology, Technical University of Munich (TUM), School of Medicine and Health, Munich, Germany
11University Medical Centre Utrecht, Utrecht, NLD
12BMT unit, CHU Rennes, Rennes, France
13Sheffield Blood & Marrow Transplant and Cellular Therapy Programme, Sheffield, United Kingdom
14Universitaetsklinikum Bonn (UKB), Bonn, Germany
15Department of Hematology, Oncology, Stem Cell Transplantation, Immune and Cell Therapy, Clinical Immunology and Rheumatology, University Hospital Bonn, Bonn, Germany
16University Hospital Maastricht, Maastricht, Netherlands
17University of Liege, Liege, Belgium
18Hopital Saint Louis, APHP, Paris, France
19Cliniques Universitaires St. Luc, Brussels, Belgium
20Radboud University Medical Centre, Nijmegen, Netherlands
21Turku University Hospital, Turku, Finland
22Department of Hematology and Transplantology, Medical University of Gdansk and University Clinical Center in Gdansk, Gdansk, Poland
23Department of Haematology, University College London Hospitals NHS Trust, London, United Kingdom
24Medical University of Warsaw, University Clinical Centre, Warsaw, Poland
25Federico II University of Naples, Hematology Department, Naples, Italy
26Unit of Bone Marrow Transplantation – Division of Hematology,, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
27Maria Skłodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, POL
28Hospital Clínico Universitario-INCLIVA, VALENCIA, Spain
29Department of Haematology, University College London Hospitals NHS Trust, London, ENG, United Kingdom

Background

Prospective randomized trials have reported a benefit for anti-thymoglobuline (ATG)-based graft-versus-host disease (GvHD) prophylaxis in the setting of allogeneic hematopoietic stem cell transplantation (alloHSCT) using unrelated donors (UD). However, the optimal GvHD prophylaxis has been recently challenged by emerging post-transplant cyclophosphamide (PTCY) data. We here present the outcomes of PTCY vs ATG as GvHD prophylaxis in myelofibrosis (MF) patients transplanted with UD from the EBMT registry.

Method

A total of 2607 MF patients transplanted from 2012 to 2022 with unrelated donors across 234 participating centers, receiving either PTCY or ATG, were included. Primary endpoints were relapse-free survival (RFS) and the cumulative incidence of aGvHD grade II-IV. Secondary endpoints included overall survival (OS) and the cumulative incidences of engraftment, relapse, non-relapse mortality (NRM), aGvHD grade III-IV and cGvHD. Cox (cause-specific) proportional hazards models were used to obtain adjusted estimates of the effect of PTCY compared to ATG on all endpoints, with a predefined set of adjustment factors (age, DIPSS, donor HLA matching, prior ruxolitinib, comorbidity score, MF subtype (PMF vs sMF)) and a frailty term for transplant center.

Results

Overall, 192 patients received PTCY and 2415 received ATG. Patients in the ATG group were older (median 61 years [IQR 55-65] vs 60 years [IQR 53-64]). Among patients with available data for DIPSS classification at alloHSCT (n=1726), there were more patients in the intermediate-II and high risk in the ATG group (59% vs 48%) than in the PTCY one. Patients in the PTCY cohort had less CMV negative patients-CMV negative donors (17% vs 34%), more patients with Karnofsky ≥90 (73% vs 64%), were more frequently transplanted from an HLA mismatched 9/10 donor (40% vs 21%) and more often transplanted in later/more recent years (42% vs 20%), PBSC as stem cell source was 96% for both.

Engraftment by day 28 was significantly better with ATG (88% vs 74.5%, p<0.001). With a median follow-up of 36.6 (95% CI 35.4 – 38.7) months, 4-year OS was 61% (53-69) with PTCY, 55.1% (53-57%) with ATG, p=0.6. 4-year RFS was 57.5% (49-66) with PTCY vs 47.3% (45-50) with ATG, p=0.2 The 4-year cumulative incidence of relapse (CIR) was 13.5% (8-19) with PTCY vs 22.9% (21-25) with ATG, p=0.07, whereas 4-year NRM was 29% (21-37%) vs 29.7% (28-32) in PTCY and ATG respectively, p=0.9. Grade II-IV aGvHD was 26.7% (20-33%) with PTCY vs 31.8% (30-34%) with ATG, p=0.15 and grade III-IV aGvHD was 14.4% (9-19%) with PTCY vs 15.3% (14-17%) with ATG, p=0.7 while there was a lower incidence at 4 years of cGvHD with PTCY, 28.4% (20-37%) vs 43.8% (42-46) with ATG, p<0.001 as well as for extensive cGvHD with 13.2% (7-20%) vs 22.1% (20-24%), p=0.02.

At multivariable analysis, there were no difference between GvHD prophylaxis groups for the primary endpoints with, for RFS, a HR with PTCY of 0.80 (0.59-1.08), p=0.15 and for aGvHD grade II-IV of 0.83 (0.58-1.19), p=0.31. However, the multivariable analysis confirmed the benefit of PTCY for cGvHD with a HR of 0.57 (0.38-0,84), p=0.005, with a tendency for extensive cGvHD with a HR of 0.58 (0.31-1.07), p=0.08 and showed a tendency of decrease relapse incidence for PTCY with a HR of 0.63 (0.38-1.05), p=0.08 as well as for GRFS with a HR of 0.80 (0.61-1.04), p=0.097.

Conclusion:

This study suggests that MF patients undergoing UD alloHSCT had a decreased incidence of cGvHD using PTCY compared to ATG as GvHD prophylaxis. PTCY is a valid option and considering availability and costs of ATG this may offer a good choice/alternative for regions which do have difficulties to have access to ATG. However, engraftment remains an issue in this setting.

Disclosures: Chalandon: Sanofi: Other: travel support, paid to the institution; Takeda: Other: advisory board paid to the institution; Medac: Other: advisory board paid to the institution; BMS: Other: advisory board and travel support, paid to the institution; Abbvie: Other: advisory board and travel support, paid to the institution; Roche: Other: advisory board and travel support, paid to the institution; Jazz: Other: advisory board and travel support, paid to the institution; Gilead: Other: advisory board and travel support, paid to the institution; Amgen: Other: advisory board and travel support, paid to the institution; Astra-Zeneca: Other: advisory board and travel support, paid to the institution; Pierre Fabre: Other: advisory board and travel support, paid to the institution; Novartis: Other: advisory board and travel support, paid to the institution; Janssen: Other: travel support, paid to the institution; Pfizer: Other: advisory board and travel support, paid to the institution; Incyte: Other: advisory board and travel support, paid to the institution; MSD: Other: advisory board and travel support, paid to the institution; Servier: Other: advisory board paid to the institution. Schetelig: Astellas: Honoraria; Medac: Honoraria; MSD: Consultancy; Novartis: Honoraria; Eurocept: Honoraria; AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Platzbecker: Amgen: Consultancy, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; MDS Foundation: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Research Funding; Curis: Consultancy, Honoraria, Research Funding; Geron: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Novartis: Consultancy, Research Funding. Yakoub-Agha: Novartis: Honoraria; Kite, a Gilead Company: Honoraria, Other: Travel Support; Janssen: Honoraria; Bristol Myers Squibb: Honoraria. Salmenniemi: Medac: Consultancy; Astella: Other: advisory board; Takeda: Other: Advisory board; AstraZeneca: Other: Advisory board; Immdica: Other: Advisory board. Snowden: BMS: Other: Advisory board; Medac: Other: Advisory board; Jazz: Other: Advisory board; Janssen: Speakers Bureau; Jazz: Speakers Bureau; Gilead: Speakers Bureau; Vertex: Other: Advisory board; Kiadis: Other: IDMC membership for clinical trial. Holderried: GlaxoSmithKline (GSK): Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Otsuka Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Other: travel expenses; Janssen: Other: travel expenses; Astellas Pharma: Other: travel expenses; Neovii: Other: travel expenses; Immatics: Other: travel expenses; Sobi: Other: travel expenses; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses. Robin: Neovii: Other: research support; Medac: Other: research support; Abbvie: Other: research support; Novartis: Other: research support. Zaucha: Takeda, BMS, Gilead, Novartis, Pfizer, Amgen, Roche, Janssen, BeiGene: Consultancy; BMS, Takeda: Research Funding; Pierre Fabre: Honoraria; Roche, AbbVie: Membership on an entity's Board of Directors or advisory committees. Drozd-Sokolowska: Novartis: Honoraria; Swixx: Honoraria, Other: Travel grant; BMS: Honoraria; Takeda: Honoraria; SOBI: Honoraria; AbbVie: Consultancy, Honoraria, Other: Travel grants; Roche: Consultancy, Honoraria; BeiGene: Consultancy; AstraZeneca: Consultancy, Honoraria, Other: Travel grants; Sanofi: Honoraria, Other: Travel grant; Janssen-Cilag: Consultancy, Honoraria. McLornan: Imago Biosciences: Research Funding; Abbvie: Honoraria; Jazz Pharma: Honoraria; Novartis: Honoraria.

*signifies non-member of ASH