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
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.
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