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4977 UM171 Expanded Cord Blood Transplantation Outcomes Compare Favorably to All Different Stem Cell Sources: An EBMT Registry Case-Control AnalysisClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, Lymphoid Leukemias, ALL, Hodgkin lymphoma, Acute Myeloid Malignancies, AML, Biological therapies, adult, Lymphomas, non-Hodgkin lymphoma, Clinical Research, Diseases, Therapies, Lymphoid Malignancies, Myeloid Malignancies, Study Population, Human, Transplantation
Monday, December 11, 2023, 6:00 PM-8:00 PM

Sandra Cohen, MD1, Myriam Labopin2*, Nadia M. Bambace, MD3, Imran Ahmad, MD4, Maude Dumont-Lagacé5*, Fabio Ciceri6*, Donal P McLornan, MD, PhD7*, Hélène Labussière-Wallet8*, Nicolaus Kröger, MD9*, Regis Peffault De Latour10*, Yves Chalandon, MD11, Edouard Forcade, MD, PhD12*, Thomas Cluzeau, MD, PhD13, Pavel Jindra14*, Aleksandr Kulagin Sr.15*, Jean Roy, MD16, Sylvie Lachance, MD17, Frederic Barabe, MD18, Pierre Caudrelier19*, Ibrahim Yakoub-Agha, MD, PhD20* and Mohamad Mohty, MD, PhD21

1Hôpital Maisonneuve-Rosemont, Université de Montréal, Institut Universitaire d'Hémato-Oncologie et de Thérapie cellulaire, Montreal, QC, Canada
2EBMT Statistical Unit, Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM UMRs 938, Paris, France
3Baptist Health South Florida, Miami Cancer Institute, Miami, FL
4Hematology-Oncology and Cell Therapy University Institute, Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, QC, CAN
5Excellthera, MontréAl, QC, CAN
6Unit of Hematology and Stem Cell Transplantation, Ospedale San Raffaele, University Vita-Salute San Raffaele, Milan, Italy
7Department of Haematology, University College London Hospitals NHS Trust, London, ENG, United Kingdom
8Hôpital Lyon Sud, Pierre Bénite, France
9University Hospital Eppendorf, Bone Marrow Transplantation Centre, Hamburg, Germany
10Hôpital Saint-Louis,, Paris, France
11Univ. Hospital of Geneva, Geneva, Switzerland
12Department of Hematology, Bordeaux University Hospital, Bordeaux, France
13Nice University Hospital, Nice, Provence Alpes Cote d'Azur, France
14Dpt. of Hemato-oncology, University Hospital Pilsen and Charles University, Pilsen, Czech Republic
15b. First State Pavlov Medical University of St. Petersburg, Raisa Gorbacheva Memorial Research Institute for Paediatric Oncology, Hematology, and Transplantation, St-Petersburg, Russia, St. Petersburg, RUS
16Maisonneuve-Rosemont Hosp., Montreal, QC, CAN
17Hopital Maisonneuve Rosemont, Institut Universitaire d'Hémato-Oncologie Greffe et Thérapie Cellulaire, Montreal, QC, CAN
18Hôpital de l'Enfant-Jésus, Division of Hematology and Medical Oncology, CHU de Québec - Université Laval, Québec, QC, Canada
19ExCellThera, Montréal, QC, Canada
20CHU de Lille, Univ Lille, INSERM U1286, Infinite, 59000, LILLE, FRA
21Hôpital Saint Antoine, Paris, FRA

Background: Cord blood (CB) transplantation (CBT) has several advantages compared with other graft sources, such as permissive human leucocyte antigen (HLA) mismatches, and low risk of chronic graft-versus-host disease (GVHD) and relapse. However, CBT has fallen into disfavor because of its high risk of non-relapse mortality (NRM) and prolonged hospitalization due to its low cell dose. Furthermore, the need for the rare large cord bloods (CBs) leads to selection of poorly HLA-matched CBs, known to further increase NRM. UM171 is a small molecule that expands hematopoietic stem cells. A phase I-II study of a single UM171-expanded, myeloablative and reduced intensity CBT for patients with high-risk hematologic malignancies who lacked a donor, demonstrated prompt neutrophil engraftment, the ability to use smaller, better HLA-matched CBs, and a low NRM of 5% (Cohen S et al. Lancet Haematol 2020). The aim of the current analysis was to compare outcomes after a UM171 CBT to real-world cohorts of 6 other stem cell sources identified in the European Society for Blood and Marrow Transplantation (EBMT) registry.

Methods: This is a retrospective study comparing 22 adults who received a single UM171-expanded CBT in the phase I-II study between 2016-2018, to 6 cohorts of patients allografted from different stem cell sources and reported to the EBMT registry. Control patients were eligible if they had received a myeloablative or reduced intensity allogeneic transplant for a hematologic malignancy in Europe during 2010-2021, were between the ages of 18-65 years, and had a Karnofsky performance status (KPS) score ≥70. The different donor control cohorts were: 1) CB, single or double units, with a calcineurin inhibitor (CNI) and mycophenolate mofetil (MMF) for GVHD prophylaxis, 2) 10/10 HLA-matched unrelated donor (MUD) peripheral blood stem cells (PBSC) with a CNI and MMF or methotrexate (MTX), 3) 10/10 MUD bone marrow (BM) with a CNI and MMF or MTX, 4) 9/10 HLA-MUD BM or PBSC (9/10 UD), 5) T cell replete haploidentical donor (haplo) BM or PBSC, and 6) matched sibling donor (MSD) BM or PBSC. Exclusion criteria included in vitro manipulated grafts and CBT recipients who received anti-thymocyte globulin or alemtuzumab. Patients were directly matched for disease and status at transplant and propensity score matching was used for prior allograft, age, KPS, and conditioning regimen. Endpoints included engraftment, GVHD, NRM, relapse, progression-free survival (PFS), overall survival (OS), and GVHD-free relapse-free survival (GRFS). The EBMT attempted to identify 3 controls for each patient. If no control was identified for a UM171 patient, the latter was excluded from the analysis.

Results: Between 17 and 21 UM171 CB patients were compared to 36 to 62 controls depending on the donor group as 1-3 controls could not be identified for each patient (Table 1). Median follow-up for the UM171 group was 36 months and generally longer for the controls. Neutrophil engraftment with UM171 CB was similar to all donor groups except slower for CB and MUD BM. Platelet engraftment was consistently slower for UM171 CB except when compared to conventional CB. The incidence of severe acute GVHD was similar across all donor groups. As there was no severe chronic GVHD in the UM171 group, the latter was associated with less extensive/severe chronic GVHD compared to MUD (PBSC and BM) and MSD. There was a trend towards lower NRM for UM171 CB compared to haplo and 9/10 UD but it did not reach statistical significance. PFS, OS and GRFS were all better with UM171 CB compared to haplo. Finally, GRFS was improved with UM171 CB when compared to MUD PBSC (Figue 1), 9/10 UD, and MSD.

Conclusions: This registry matched case-control analysis demonstrated real-word evidence suggesting UM171-expanded CBT recipients have improved outcomes compared to other donor types. More specifically and due to the absence of severe chronic GVHD with UM171 CB, GRFS was better with UM171 CB when compared to other graft sources except for CB and MUD BM. Also, OS and PFS were superior with UM171 CB compared to haplo donors. Limitations of this study included the small number of UM171 patients, the inability to identify controls for each case, and certain missing data for the controls. UM171 expansion of CB appeared to achieve the desired outcome of maintaining benefits of CB while removing its disadvantages. Thus, prospective randomized studies are warranted to confirm these results.

Disclosures: Cohen: ExCellThera: Consultancy, Honoraria, Patents & Royalties: Royalties if sales of UM171 (ExCellThera), Research Funding. Dumont-Lagacé: ExCellThera: Consultancy, Current Employment. Ciceri: ExCellThera: Other: Scientific Advisory Board . McLornan: Jazz Pharma: Honoraria; EBMT Scientific Council Member: Other: Chair of EBMT CMWP; UK ALL RIC TRIAL - DSM board: Other: participation on a data safety monitoring board or advisory board; Abbvie: Honoraria; Novartis: Honoraria; Imago Biosciences: Research Funding. Kröger: Kite/Gilead: Honoraria; Jazz: Honoraria; MSD: Honoraria; Neovii Biotech: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Riemser: Honoraria, Research Funding; Pfizer: Honoraria; BMS: Honoraria, Research Funding; Takeda: Consultancy; Sanofi: Honoraria. Peffault De Latour: Jazz Pharmaceuticals: Honoraria. Chalandon: MSD: Honoraria, Other: travel support; Servier: Honoraria; BMS: Honoraria, Other: travel support; Incyte: Honoraria, Other: travel support; Roche: Honoraria, Other: travel support; Astra-Zeneca: Honoraria, Other: travel support; Abbvie: Honoraria, Other: travel support; Janssen: Other: travel support; Amgen: Honoraria, Other: travel support; Gilead: Honoraria, Other: travel support; Jazz: Honoraria, Other: travel support, Speakers Bureau; Pfizer: Honoraria; Novartis: Honoraria, Other: travel support; Sanofi: Other: travel support. Cluzeau: Syros: Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau; Keros: Speakers Bureau; Servier: Consultancy, Speakers Bureau; Incyte: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Jindra: Janssen: Honoraria, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Roy: Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; ExCellThera: Patents & Royalties, Research Funding. Lachance: ExCellThera: Patents & Royalties: Royalties if sales of UM171 (ExCellThera). Caudrelier: ExCellThera: Current Employment, Other: Chief Medical Officer . Yakoub-Agha: Bristol Myers Squibb: Honoraria; Janssen: Honoraria; Kite, a Gilead Company: Honoraria, Other: travel support; Novartis: Honoraria. Mohty: JAZZ PHARMACEUTICALS: Honoraria, Research Funding.

*signifies non-member of ASH