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. 2024 Oct 24;144(17):1834-1845.
doi: 10.1182/blood.2023023660.

Abatacept for acute graft-versus-host disease prophylaxis after unrelated donor hematopoietic cell transplantation

Leslie S Kean  1   2   3 , Linda J Burns  4 , Tzuyung D Kou  5 , Roxanne Kapikian  5   6 , Karissa Lozenski  5 , Amelia Langston  7 , John T Horan  8 , Benjamin Watkins  9 , Muna Qayed  10 , Brandi Bratrude  1 , Kayla Betz  1 , Xiao-Ying Tang  4 , Mei-Jie Zhang  4 , Sean E Connolly  5 , Martin Polinsky  5 , Brian Gavin  5 , Andres Gomez-Caminero  5 , Marcelo C Pasquini  4
Affiliations

Abatacept for acute graft-versus-host disease prophylaxis after unrelated donor hematopoietic cell transplantation

Leslie S Kean et al. Blood. .

Abstract

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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Conflict of interest statement

Conflict-of-interest disclosure: L.S.K. is on the scientific advisory board for Mammoth Biosciences and HiFiBio; received research funding from Magenta Therapeutics, Tessera Therapeutics, Novartis, EMD Serono, Gilead Pharmaceuticals, and Regeneron Pharmaceuticals; received consulting fees from Vertex; received grants/personal fees from Bristol Myers Squibb; and reports royalties/partial funding for this study from Bristol Myers Squibb. L.S.K.’s conflict-of-interest with Bristol Myers Squibb is managed under an agreement with Harvard Medical School. L.J.B. received research collaborations with Astellas, bluebird bio, Gamida Cell, Kyowa Kirin, Mesoblast, Sanofi, and Vertex; and received a research contract through her institution for this study with Bristol Myers Squibb. S.E.C. and M.P. are employees and shareholders of Bristol Myers Squibb. R.K. is a current employee of Cytel; was on a work-share agreement with Bristol Myers Squibb during the time of analysis; and is a shareholder of Bristol Myers Squibb. A.L. received a medical writing support and a research contract for this study with Bristol Myers Squibb. M.Q. received honoraria from Novartis and Vertex; and received medical writing support from Bristol Myers Squibb. X.-Y.T. received support and payment to their institution from Bristol Myers Squibb; and is an immediate family member of an employee and shareholder of Kite Pharma. B.G. received consulting fees from WebMD, LLC; and is a former employee of (within 36 months) and shareholder of Bristol Myers Squibb. M.C.P. received research support from Bristol Myers Squibb; received grants/contracts from Bristol Myers Squibb, Kite Pharma, Novartis, and Janssen; and reports payments/honoraria for lectures from Kite Pharma. K.L., T.D.K., and A.G.-C. are former Bristol Myers Squibb employees (within 36 months) and shareholders of Bristol Myers Squibb. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Two-year OS and RFS in 7/8 HLA-MMUD HCT weighted samples. OS with abatacept + CNI/MTX compared with CNI/MTX (A), CNI/MTX + ATG (B), and PT-Cy∗ (C) and RFS with abatacept + CNI/MTX compared with CNI/MTX (D), CNI/MTX + ATG (E), and PT-Cy∗ (F). Propensity scores were obtained from a logistic regression model including sex, disease, age, HCT graft source, conditioning intensity, Karnofsky/Lansky performance score, and CNI type as covariates. Based on weighted Kaplan-Meier method. Symbols represent censored observation. Patients were censored at 2 years after transplant or at time of last follow-up, whichever occurred earlier. Tables under each curve show the number of weighted patients at risk at each time point. ∗For PT-Cy, propensity scores obtained from a logistic regression model including sex, disease, age, HCT graft source, conditioning intensity, and performance score as covariates. Adapted from Kean et al., , ,
Figure 2.
Figure 2.
Two-year OS and RFS in 8/8 HLA-MUD HCT weighted samples. OS with abatacept + CNI/MTX compared with CNI/MTX (A), CNI/MTX + ATG (B), and PT-Cy∗ (C) and RFS with abatacept + CNI/MTX compared with CNI/MTX (D), CNI/MTX + ATG (E), and PT-Cy∗ (F). Propensity scores obtained from a logistic regression model including sex, disease, age, HCT graft source, conditioning intensity, Karnofsky/Lansky performance score, and CNI type as covariates. Based on weighted Kaplan-Meier method. Symbols represent censored observation. Patients were censored at 1 year after transplant or at time of last follow-up, whichever occurred earlier. Tables under each curve show the number of weighted patients at risk at each time point. ∗For PT-Cy, propensity scores obtained from a logistic regression model including age and conditioning intensity as covariates. Adapted from Kean et al., , ,
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