Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD

Benjamin Watkins, Muna Qayed, Courtney McCracken, Brandi Bratrude, Kayla Betz, Yvonne Suessmuth, Alison Yu, Shauna Sinclair, Scott Furlan, Steven Bosinger, Victor Tkachev, James Rhodes, Audrey Grizzle Tumlin, Alexandria Narayan, Kayla Cribbin, Scott Gillespie, Ted A. Gooley, Marcelo C. Pasquini, Kyle Hebert, Urvi KapoorAndre Rogatko, Mourad Tighiouart, Sungjin Kim, Catherine Bresee, Sung W. Choi, Jeffrey Davis, Christine Duncan, Roger Giller, Michael Grimley, Andrew C. Harris, David Jacobsohn, Nahal Lalefar, Maxim Norkin, Nosha Farhadfar, Michael A. Pulsipher, Shalini Shenoy, Aleksandra Petrovic, Kirk R. Schultz, Gregory A. Yanik, Edmund K. Waller, John E. Levine, James L. Ferrara, Bruce R. Blazar, Amelia Langston, John T. Horan, Leslie S. Kean

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


PURPOSE: Severe (grade 3-4) acute graft-versus-host disease (AGVHD) is a major cause of death after unrelated-donor (URD) hematopoietic cell transplant (HCT), resulting in particularly high mortality after HLA-mismatched transplantation. There are no approved agents for AGVHD prevention, underscoring the critical unmet need for novel therapeutics. ABA2 was a phase II trial to rigorously assess safety, efficacy, and immunologic effects of adding T-cell costimulation blockade with abatacept to calcineurin inhibitor (CNI)/methotrexate (MTX)-based GVHD prophylaxis, to test whether abatacept could decrease AGVHD.

METHODS: ABA2 enrolled adults and children with hematologic malignancies under two strata: a randomized, double-blind, placebo-controlled stratum (8/8-HLA-matched URD), comparing CNI/MTX plus abatacept with CNI/MTX plus placebo, and a single-arm stratum (7/8-HLA-mismatched URD) comparing CNI/MTX plus abatacept versus CNI/MTX CIBMTR controls. The primary end point was day +100 grade 3-4 AGVHD, with day +180 severe-AGVHD-free-survival (SGFS) a key secondary end point. Sample sizes were calculated using a higher type-1 error (0.2) as recommended for phase II trials, and were based on predicting that abatacept would reduce grade 3-4 AGVHD from 20% to 10% (8/8s) and 30% to 10% (7/8s). ABA2 enrolled 142 recipients (8/8s, median follow-up = 716 days) and 43 recipients (7/8s, median follow-up = 708 days).

RESULTS: In 8/8s, grade 3-4 AGVHD was 6.8% (abatacept) versus 14.8% (placebo) ( P = .13, hazard ratio = 0.45). SGFS was 93.2% (CNI/MTX plus abatacept) versus 82% (CNI/MTX plus placebo, P = .05). In the smaller 7/8 cohort, grade 3-4 AGVHD was 2.3% (CNI/MTX plus abatacept, intention-to-treat population), which compared favorably with a nonrandomized matched cohort of CNI/MTX (30.2%, P < .001), and the SGFS was better (97.7% v 58.7%, P < .001). Immunologic analysis revealed control of T-cell activation in abatacept-treated patients.

CONCLUSION: Adding abatacept to URD HCT was safe, reduced AGVHD, and improved SGFS. These results suggest that abatacept may substantially improve AGVHD-related transplant outcomes, with a particularly beneficial impact on HLA-mismatched HCT.

Original languageEnglish (US)
Pages (from-to)1865-1877
Number of pages13
JournalJournal of Clinical Oncology
Issue number17
StatePublished - Jun 10 2021

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© 2021 by American Society of Clinical Oncology.


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