Ptcy Overcomes HLA Mismatch in Unrelated Donor Transplant for Acute Lymphoblastic Leukemia: A Study from the ALWP of the EBMT

Sanz, Jaime

Oral and Poster Abstracts
732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster II

Adult, Acute Myeloid Malignancies, AML, Research, Clinical Research, Diseases, Treatment Considerations, Registries, Myeloid Malignancies, Human, Study Population

Jaime Sanz¹^*, Allain-Thibeault Ferhat²^*, Aleksander Kulagin³^*, Nicolaus Kröger, MD⁴^*, Montserrat Rovira, MD, PhD^5,6^*, Lorenzo Lazzari⁷^*, Mutlu Arat⁸^*, Juan Montoro, MD, PhD⁹^*, Jurjen Versluis, MD, PhD¹⁰^*, Péter Pál Reményi, MD¹¹^*, Simona Sica, MD, PhD¹²^*, Didier Blaise, MD¹³^*, Muhammad Saif¹⁴^*, Jan Vydra, MD, PhD¹⁵^*, Franca Fagioli, MD, PhD¹⁶^*, Erfan Nur, MD, PhD¹⁷, Sebastian Giebel, MD, PhD¹⁸^*, Simona Piemontese¹⁹^*, Mohamad Mohty, MD, PhD²⁰ and Fabio Ciceri, MD^21,22^*

¹Hematology Department, Hospital Universitari i Politècnic La Fe, Departament de Medicina Universitat de Valencia, CIBERONC, Instituto Carlos III, Spain, VALENCIA, Spain
²EBMT Statistical Unit, Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France
³5RM Gorbacheva Research Institute, Pavlov University, St Petersburg, RUS
⁴University Medical Center Hamburg, Hamburg, Germany
⁵Hematopoietic Transplantation Unit, Hematology Department, Clinical Institute of Hematology and Oncology (ICMHO), Hospital Clínic de Barcelona, Barcelona, Spain
⁶Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain
⁷Hematology Department - *cofirst author, IRCCS Ospedale San Raffaele, Milano, ITA
⁸Demiroglu Bilim University Istanbul Florence Nightingale Hospital, Istanbul, Turkey
⁹Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
¹⁰Erasmus University Medical Center Cancer Institute, Rotterdam, Netherlands
¹¹Department of Hematology and Stem Cell Transplantation, Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary
¹²Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Rome, Italy
¹³Programme de Transplantation & Therapie Cellulaire, Marseille, France
¹⁴The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, GBR
¹⁵Institute of Haematology and Blood Transfusion, Prague, Czech Republic
¹⁶Ospedale Infantile Regina Margherita, Torino, Italy, Torino, Italy
¹⁷Department of Hematology, Amsterdam UMC location University of Amsterdam, Amsterdam, Netherlands
¹⁸Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
¹⁹Hematology and Bone Marrow transplant Unit, San Raffaele Scientific Institute IRCCS, Milano, Milano, Italy
²⁰Sorbonne University, Hôpital Saint-Antoine, and INSERM UMRs938, Paris, France
²¹Hematology and Bone Marrow Transplantation Unit, I.R.C.C.S. San Raffaele Scientific Institute, Milan, Italy
²²Vita-Salute San Raffaele University, Milan, Italy

Background: Post-transplant cyclophosphamide (PTCy) seems to mitigate the disparity in outcomes between use of matched (MUD) or mismatched Unrelated Donors (MMUD) hematopoietic stem cell transplantation (HSCT), but there are no specific studies in patients with acute lymphoblastic leukemia (ALL).

Methods: We retrospectively analyzed the characteristics of 8/8 MUD and 7/8 MMUD that may affect transplant outcomes in patients with ALL in complete remission (CR) who received a first peripheral blood allogeneic HSCT with PTCy between January 2010 and December 2022, registered in the EBMT database. The primary endpoint was leukemia-free survival (LFS).

Results: Overall, 350 patients were included with a median age of 37 years (range, 18-76), and 231 (66%) were in first CR. 280 (80%) patients had B-cell ALL of which 101 (29%) were Philadelphia positive. Regarding donors, median age was 28.8 years (range, 18-57), 237 (68%) were MUDs and 113 (32%) were MMUDs. Patient, donor and transplant characteristics were equally distributed across donor types except for older donor age, more frequent recipient male sex (58%) and use of TBI containing myeloablative conditioning in MMUD transplants (55%). The 180-day cumulative incidence of acute graft-versus-host disease (GVHD) grade II-IV and III-IV was 28% (95% CI 23-33) and 9% (95% CI 6-12), respectively, while the 2-year cumulative incidence of chronic and chronic extensive GVHD was 28% (95% CI 23-34) and 12% (95% CI 9-17), respectively. After a median follow-up of 24 months, the cumulative incidence of relapse and non-relapse mortality and the probabilities of LFS, overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were 24% (95% CI 19-29), 15% (95% CI 11-19), 62% (95% CI 56-67), 73% (95% CI 67-78) and 48% (95% CI 42-54), respectively. The use of MUD or MMUD did not have a significant impact on LFS (hazard ratio [HR] 0.84; 95% CI 0.56-1.24) or any other transplant outcomes. Considering other donor related variables, the use of female donor to male recipient increased the risk of acute GvHD grade II-IV (HR 1.78; 95% CI 1.05-3, p=0.03) and the use of older donor age increased grade III-IV (HR 1.7; 95% CI 1.1-2.64, p=0.02). Additionally, CMV-neg donor for CMV-neg recipient was associated with improved LFS (HR 0.55; 95% CI 0.32-0.96, p=0.034) and overall survival (HR 0.52; 95% CI 0.28-1,p=0.49).

Conclusions: For patients undergoing HSCT from an unrelated donor with PTCy for ALL in CR the use of MMUDs does not negatively affect outcomes. Other donor related variables such as age, gender and CMV serostatus might be prioritized over HLA match considerations.

Disclosures: 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. Versluis: Novartis: Honoraria; Abbvie: Honoraria; Rigel: Membership on an entity's Board of Directors or advisory committees; ExcelThera: Membership on an entity's Board of Directors or advisory committees. Nur: Novartis: Research Funding; vertex: Speakers Bureau. Giebel: Beigene: Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Sobi: Consultancy, Honoraria, Other: Travel funding, Speakers Bureau; Kite/Gilead: Consultancy, Honoraria, Speakers Bureau; Astra Zeneca: Honoraria, Speakers Bureau. Mohty: Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria; GSK: Honoraria; Pfizer: Consultancy, Current holder of stock options in a privately-held company, Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria; Novartis: Honoraria; Stemline Menarini: Honoraria; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria; Adaptive: Honoraria; 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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3570 Ptcy Overcomes HLA Mismatch in Unrelated Donor Transplant for Acute Lymphoblastic Leukemia: A Study from the ALWP of the EBMT