Improved Overall Survival of Patients Treated with Abatacept in Combination with a Calcineurin Inhibitor and Methotrexate Following 7/8 HLA-Matched Unrelated Allogeneic Hematopoietic Stem Cell Transplantation: Analysis of the Center for International Blood and Marrow Transplant Research Database

Introduction: Acute graft versus host disease (aGVHD) is the most common cause of early non-relapse mortality following allogeneic hematopoietic stem cell transplantation (HSCT; McDonald-Hyman C, et al. Sci Transl Med 2015). aGVHD is caused by a series of complex interactions between donor T cells and recipient antigen-presenting cells that result in immune-mediated tissue damage in HSCT recipients. Inhibition of T-cell costimulation has been recognized as a highly effective approach to preventing T-cell allo-activation (McDonald-Hyman C, et al. Sci Transl Med 2015; Koura DT, et al. Biol Blood Marrow Transplant 2013). Abatacept, a CTLA-4-IgG1 fusion protein, binds to CD80/86 on antigen-presenting cells and inhibits CD28 costimulatory signaling required for T-cell activation (Malmstrom V, et al. Nat Rev Immunol 2017). A phase 2 study (ClinicalTrials.gov: NCT01743131) reported 73.6% (80% confidence interval [CI]: 62.0-82.2) overall survival (OS) at 2 years in recipients of a 7/8 human leukocyte antigen (HLA)-single mismatch unrelated donor (7/8 MMUD) HSCT following treatment with abatacept + a standard aGVHD prophylaxis regimen (calcineurin inhibitor [CNI] + methotrexate [MTX] without [−] antithymocyte globulin [ATG]), compared with 45.3% (80% CI: 39.3-51.1; P = 0.002) in a standard treatment cohort (CNI + MTX − ATG) of matched controls from the Center for International Blood and Marrow Transplant Research (CIBMTR; Watkins B, et al. J Clin Oncol 2021). The aim of this current real-world analysis was to further evaluate the impact of abatacept on survival of 7/8 MMUD HSCT recipients, treated with CNI + MTX − ATG with or without abatacept, from the CIBMTR database of all allogeneic HSCTs performed in the United States in recent years.