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Abatacept plus calcineurin inhibitors/methotrexate (CNI/MTX) is the first US Food and Drug Administration (FDA)-approved regimen for acute graft-versus-host disease (aGVHD) prophylaxis during unrelated-donor hematopoietic cell transplantation (URD-HCT). Using Center for International Blood and Marrow Transplant Research data, we investigated its impact in patients receiving 7/8 HLA-mismatched unrelated donor (MMUD) or 8/8 HLA-matched unrelated donor (MUD) URD-HCT between 2011 and 2018. Primary outcomes included day-180, 1-year, and 2-year overall survival (OS) and relapse-free survival (RFS) for abatacept + CNI/MTX vs CNI/MTX, CNI/MTX + antithymocyte globulin (ATG), and posttransplant cyclophosphamide-based prophylaxis (PT-Cy). For 7/8 MMUDs, day-180 OS (primary end point supporting FDA approval) was significantly higher for abatacept + CNI/MTX vs CNI/MTX (98% vs 75%; P = .0028). Two-year RFS was significantly higher for abatacept + CNI/MTX vs CNI/MTX (74% vs 49%; P = .0098) and CNI/MTX + ATG (77% vs 35%; P = .0002), and similar vs PT-Cy (72% vs 56%; P = .1058). For 8/8 MUDs, 2-year RFS for abatacept + CNI/MTX was numerically higher vs CNI/MTX (63% vs 52%; P = .1497), with an improved hazard ratio (HR) of 0.46 (0.25-0.86), and vs CNI/MTX + ATG (66% vs 55%; P = .1193; HR, 0.39 [0.21-0.73]), and was similar vs PT-Cy (68% vs 57%; P = .2356; HR, 0.54 [0.26-1.11]). For 7/8 MMUD and 8/8 MUD recipients, abatacept + CNI/MTX prophylaxis improved survival outcomes vs CNI/MTX and CNI/MTX + ATG; outcomes were similar to PT-Cy-based regimens. Abatacept + CNI/MTX may facilitate unrelated donor pool expansion for HCT.
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http://dx.doi.org/10.1182/blood.2023023660 | DOI Listing |
Transplant Cell Ther
July 2025
Hans Messner Allogeneic Blood and Marrow Transplant Program, Princess Margaret Cancer Center, Toronto, Canada; Temerty Faculty of Medicine, University of Toronto, Toronto, Canada. Electronic address:
Female-to-male (F→M) sex-mismatched allogeneic hematopoietic stem cell transplantation (HSCT) is known to increase the risk of graft-versus-host disease (GVHD). We evaluated the impact of donor-recipient sex mismatch on GVHD incidence and assessed the efficacy of combined low-dose antithymocyte globulin (ATG) (2mg/kg) and post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis compared to calcineurin inhibitor-methotrexate/mycophenolate mofetil (CNI-MTX/MMF). We retrospectively analyzed 861 HSCT recipients, with acute myeloid leukemia as the predominant indication (82%).
View Article and Find Full Text PDFClin Cancer Res
August 2025
Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
In December 2021, the FDA approved abatacept (Orencia; Bristol Myers Squibb) in combination with a calcineurin inhibitor (CNI) and methotrexate (MTX) as the first drug for the prophylaxis of acute GVHD (aGVHD) in adult and pediatric (2 years of age and older) patients undergoing hematopoietic stem cell transplantation (HSCT) from a matched or one allele-mismatched unrelated donor (URD). Study IM101311 included a randomized (1:1), double-blind evaluation of abatacept (N = 73) versus placebo (N = 69) +CNI+MTX as aGVHD prophylaxis in patients ≥6 years undergoing an 8/8 HLA-matched URD HSCT. Overall survival and grade II-IV aGVHD-free survival at day 180 after transplantation for abatacept versus placebo showed HRs [95% confidence interval (CI)] of 0.
View Article and Find Full Text PDFTransplant Cell Ther
August 2025
Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut. Electronic address:
Prior analyses have reported on the impact of different donor types and conditioning regimen intensities on outcomes for patients with sickle cell disease (SCD) who undergo hematopoietic cell transplantation (HCT), and demonstrated superior outcomes using an HLA-matched related donor (MRD). However, the impact of conditioning regimen intensity on outcomes remains unclear, with conflicting findings across studies. In addition, the lack of data on comparative outcomes of different approaches to conditioning and graft-versus-host disease (GVHD) prophylaxis for allogeneic HCT for SCD remains a gap in the field.
View Article and Find Full Text PDFBlood Adv
February 2025
Hans Messner Allogeneic Blood and Marrow Transplant Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.
Posttransplant cyclophosphamide (PTCy) is a promising graft-versus-host disease (GVHD) prophylaxis in haploidentical and matched unrelated donor hematopoietic stem cell transplantation (HSCT), but its role in matched sibling donor (MSD) transplants remains unclear. We conducted a retrospective study of 413 MSD-HSCT patients receiving peripheral blood stem cell (PBSC) grafts from January 2010 to January 2023. Patients were categorized into 4 groups: group I (calcineurin inhibitor [CNI] + methotrexate [MTX] or mycophenolate mofetil [MMF]), group II (CNI + MTX or MMF + antithymocyte globulin [ATG]), group III (PTCy + ATG + CNI), and group IV (PTCy + CNI + MMF).
View Article and Find Full Text PDFBlood
October 2024
Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin Clinical Cancer Center, Medical College of Wisconsin, Milwaukee, WI.
Abatacept plus calcineurin inhibitors/methotrexate (CNI/MTX) is the first US Food and Drug Administration (FDA)-approved regimen for acute graft-versus-host disease (aGVHD) prophylaxis during unrelated-donor hematopoietic cell transplantation (URD-HCT). Using Center for International Blood and Marrow Transplant Research data, we investigated its impact in patients receiving 7/8 HLA-mismatched unrelated donor (MMUD) or 8/8 HLA-matched unrelated donor (MUD) URD-HCT between 2011 and 2018. Primary outcomes included day-180, 1-year, and 2-year overall survival (OS) and relapse-free survival (RFS) for abatacept + CNI/MTX vs CNI/MTX, CNI/MTX + antithymocyte globulin (ATG), and posttransplant cyclophosphamide-based prophylaxis (PT-Cy).
View Article and Find Full Text PDF