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
Year: 2024
Type: conference-abstract
Abstract: 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.
Source: Blood
Authors: Yves Chalandon, Edouard F. Bonneville, Liesbeth C. de Wreede, Linda Koster, Joe Tuffnell, Jakob Passweg, Johannes Schetelig, Uwe Platzbecker, Ibrahim Yakoub-Agha, Urpu Salmenniemi, Mareike Verbeek, Moniek De Witte, Jean-Baptiste Méar, John Snowden, Tobias A.W. Holderried, Gwendolyn Van Gorkom, Frederic Baron, Marie Robin, Xavier Poiré, Mieke Roeven, Maija Itälä-Remes, Jan Maciej Zaucha, Kavita K Raj, Joanna Drozd-Sokolowska, Giorgia Battipaglia, Nicola Polverelli, Tomasz Czerw, Juan Carlos Hernandez Boluda, Donal P McLornan
Institutions: University Hospital of Geneva, Leiden University Medical Center, European Society for Blood and Marrow Transplantation, University Hospital of Basel, University Hospital Carl Gustav Carus, Technische Universität Dresden, University Hospital Leipzig, Leipzig University, Inserm, Université de Lille, Centre Hospitalier Universitaire de Lille, Institute for Translational Research in Inflammation, Helsinki University Hospital, TUM Klinikum, Technical University of Munich, University Medical Center Utrecht, Centre Hospitalier Universitaire de Rennes, University of Bonn, University Hospital Bonn, Maastricht University Medical Centre, University of Liège, Assistance Publique – Hôpitaux de Paris, Hôpital Saint-Louis, Cliniques Universitaires Saint-Luc, Radboud University Medical Center, Turku University Hospital, University Clinical Centre, Gdańsk Medical University, University College London Hospitals NHS Foundation Trust, University College London, Medical University of Warsaw, Federico II University Hospital, University of Naples Federico II, Policlinico San Matteo Fondazione, The Maria Sklodowska-Curie National Research Institute of Oncology
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4405039946