Abatacept for graft versus host disease prophylaxis in patients 60 years and older receiving mismatched unrelated donor transplantation for hematologic malignancies

• Type of Material: Article
• Authors: Sharmila Raghunandan, Emory University; Muna Qayed, Emory University; Benjamin Watkins, Emory University; Michael Graiser, Emory University; Lev Gorfinkel, Dana-Farber Cancer Institute; Adrianna Lynn Westbrook, Emory University; Scott E. Gillespie, Emory University; Brandi Bratrude, Boston Children's Hospital; Yvonne Suessmuth, Emory University; John Horan, Dana-Farber Cancer Institute; Leslie S. Kean, Dana-Farber Cancer Institute; Amelia A Langston, Emory University
• Language: English
• Date: 2023-08-14
• Publisher: Springer Nature
• Publication Version: Final Published Version
• Copyright Statement: © 2023, The Author(s)
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1038/s41409-023-02043-y
• Title of Journal or Parent Work: Bone Marrow Transplantation
• Volume: 58
• Issue: 11
• Start Page: 1264
• End Page: 1266
• Keywords: transplant related mortality; acute graft-versus-host-disease; cytotoxic T-cell lymphocyte-4-immunoglobulin; Allogeneic hematopoietic cell transplant
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Immunology

Abstract

Allogeneic hematopoietic cell transplant (HCT) remains the best option for a cure for many patients with hematologic malignancies, but is associated with significant morbidity and mortality, particularly for older patients. In the absence of a matched related or unrelated donor, a mismatched unrelated donor (MMUD) increases donor options, particularly for Black and Latinx patients. MMUD HCTs have historically been associated with an increased risk of severe acute graft-versus-host-disease (aGVHD), resulting in increased transplant related mortality (TRM) and decreased overall survival (OS) when compared with matched related or unrelated donor HCTs [1–4]. Abatacept, cytotoxic T-cell lymphocyte-4-immunoglobulin (CTLA4-Ig), is a T-cell co-stimulation blockade agent [5] that was granted FDA approval for the prevention of aGVHD in patients receiving unrelated donor HCT in part based on results of the Abatacept 2 trial (ABA2, NCT01743131). ABA2 was a multicenter phase II trial that evaluated abatacept in addition to standard GVHD prophylaxis with a calcineurin inhibitor and methotrexate (CNI/MTX) for GVHD prevention in 8/8 HLA-matched unrelated donor (MUD) HCT and 7/8 MMUD HCT. Patients in the 7/8 MMUD cohort were assigned to a single arm open label stratum compared to a prespecified Center for International Blood and Marrow Transplant Research (CIBMTR) cohort and demonstrated a significant reduction in grade 3–4 aGVHD compared with the CIBMTR cohort receiving CNI/MTX alone. The lower rates of grade 3–4 aGVHD translated into significant improvement in TRM and OS at 2 years for patients receiving abatacept [6]. The ABA2 trial enrolled patients 6–76 years of age in the 7/8 MMUD analysis, but outcomes were not reported separately for patients over 60 years of age. This age group is at increased risk of TRM [7, 8] that is further compounded by a MMUD HCT and the epidemiology of myeloid malignancies. Therefore, the goal of this analysis was to evaluate outcomes in patients 60 years and older undergoing MMUD HCT for hematologic malignancies.