Phase 1 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease

Myrna R. Nahas, Robert J. Soiffer, Haesook T. Kim, Edwin P. Alyea III, Jon Arnason, Robin Joyce, Joseph H. Antin, Vincent T. Ho, Dina Stroopinsky, Shuli Li, James D. Levine, Malgorzata McMasters, Salvia Jain, Ayad Hamdan, Dimitrios Tzachanis, Mary Paty Bryant, Emma K. Logan, Josie Bazemore, Jeremy Stewart, Amy Joyce, Susan Stephenson, Abigail Washington, Leandra Cole, Athalia Pyzer, Rebecca Karp Leaf, David E. Avigan and Jacalyn Rosenblatt

Key Points

  • Costimulatory blockade using abatacept represents a novel therapeutic approach for the treatment of cGVHD.

  • Abatacept resulted in a clinical response in 44% of patients with both decreased prednisone use and T-cell PD-1 expression in responders.


Steroid-refractory chronic graft-versus-host disease (SR-cGVHD) remains a major cause of morbidity and mortality after allogeneic stem cell transplantation. Innovative immunotherapeutic strategies are urgently needed for the treatment of SR-cGVHD. We conducted a phase 1 clinical trial to evaluate the safety, efficacy, and immune effects of abatacept, a novel immunomodulatory drug that acts as an inhibitor of T-cell activation via costimulatory blockade, in the treatment of SR-cGVHD. The study followed a 3+3 design with 2 escalating abatacept doses: 3 mg/kg and 10 mg/kg, with an expansion cohort treated at 10 mg/kg. Abatacept was well-tolerated with no dose-limiting toxicities. Of the 16 evaluable patients, 44% achieved a clinical partial response per 2005 National Institutes of Health Consensus Criteria. Importantly, abatacept resulted in a 51.3% reduction in prednisone usage in clinical responders (mean baseline, 27 vs 14 mg; P = .01). Increased PD-1 expression on circulating CD4 (P = .009) and CD8 (P = .007) T cells was observed in clinical responders. In summary, abatacept was safe and led to a marked improvement in National Institutes of Health cGVHD scores and a significant reduction in prednisone use. In this cohort of heavily pretreated patients, the results suggest abatacept may be a promising therapeutic agent for SR-cGVHD, and a phase 2 trial has been initiated. This trial was registered at as #NCT01954979.

  • Submitted May 11, 2017.
  • Accepted March 7, 2018.
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