In vivo T cell costimulation blockade with abatacept for acute graft-versus-host disease prevention: a first-in-disease trial.

Published

Journal Article

We performed a first-in-disease trial of in vivo CD28:CD80/86 costimulation blockade with abatacept for acute graft-versus-host disease (aGVHD) prevention during unrelated-donor hematopoietic cell transplantation (HCT). All patients received cyclosporine/methotrexate plus 4 doses of abatacept (10 mg/kg/dose) on days -1, +5, +14, +28 post-HCT. The feasibility of adding abatacept, its pharmacokinetics, pharmacodynamics, and its impact on aGVHD, infection, relapse, and transplantation-related mortality (TRM) were assessed. All patients received the planned abatacept doses, and no infusion reactions were noted. Compared with a cohort of patients not receiving abatacept (the StdRx cohort), patients enrolled in the study (the ABA cohort) demonstrated significant inhibition of early CD4(+) T cell proliferation and activation, affecting predominantly the effector memory (Tem) subpopulation, with 7- and 10-fold fewer proliferating and activated CD4(+) Tem cells, respectively, at day+28 in the ABA cohort compared with the StdRx cohort (P < .01). The ABA patients demonstrated a low rate of aGVHD, despite robust immune reconstitution, with 2 of 10 patients diagnosed with grade II-IV aGVHD before day +100, no deaths from infection, no day +100 TRM, and with 7 of 10 evaluable patients surviving (median follow-up, 16 months). These results suggest that costimulation blockade with abatacept can significantly affect CD4(+) T cell proliferation and activation post-transplantation, and may be an important adjunct to standard immunoprophylaxis for aGVHD in patients undergoing unrelated-donor HCT.

Full Text

Duke Authors

Cited Authors

  • Koura, DT; Horan, JT; Langston, AA; Qayed, M; Mehta, A; Khoury, HJ; Harvey, RD; Suessmuth, Y; Couture, C; Carr, J; Grizzle, A; Johnson, HR; Cheeseman, JA; Conger, JA; Robertson, J; Stempora, L; Johnson, BE; Garrett, A; Kirk, AD; Larsen, CP; Waller, EK; Kean, LS

Published Date

  • November 2013

Published In

Volume / Issue

  • 19 / 11

Start / End Page

  • 1638 - 1649

PubMed ID

  • 24047754

Pubmed Central ID

  • 24047754

Electronic International Standard Serial Number (EISSN)

  • 1523-6536

International Standard Serial Number (ISSN)

  • 1083-8791

Digital Object Identifier (DOI)

  • 10.1016/j.bbmt.2013.09.003

Language

  • eng