Treatment with abatacept was well tolerated, associated with a 58% overall response rate (ORR), and led to a durable reduction in prednisone dose in patients with steroid-refractory chronic graft vs host disease (cGVHD) after allogeneic transplant, according to research published in Blood.

“Abatacept is the first of a class of agents called selective costimulation modulators that is used for the treatment of rheumatologic diseases, such as rheumatoid arthritis,” the authors wrote in their report. “The immunomodulatory role of abatacept has already led to its approval in combination with a calcineurin inhibitor and methotrexate for prophylaxis of acute GVHD.”

The researchers conducted a phase 2 study to evaluate the efficacy and tolerability of abatacept in steroid-refractory cGVHD ( ID: NCT01954979). The primary endpoint was the ORR (complete response [CR] or partial response [PR]).

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A total of 39 patients with progressive steroid-refractory cGVHD (median age, 62 years; range, 25-77; 53.8% female) were treated with 6 doses of abatacept (IV 10 mg/kg each; doses 1-3, every 2 weeks, then doses 4-6, every 4 weeks).

Most patients received hematopoietic cell transplant (HCT) for the treatment of acute myeloid leukemia (46.2%), myelodysplastic syndrome (20.5%), and acute lymphoblastic leukemia (12.8%).

The median time from HCT to study entry was 43 months (range, 6-173). At baseline, 46% of patients had moderate cGVHD, and 54% of patients had severe cGVHD (2014 NIH consensus criteria). cGVHD assessment showed organ involvement of the skin in 85%, mouth in 44%, eyes in 72%, GI tract in 15%, liver in 23%, lung in 56%, and joints in 82%.

Among 36 evaluable patients, the ORR was 58%, with all responders achieving a PR. Organ-specific response rates with the greatest improvement (either CR or PR) included lung (57%), liver (54%), GI tract (50%), and mouth (42%). Progression of cGVHD occurred in 33% of patients, including in skin (6%), mouth (26%), eyes (4%), liver (9%), lung (13%), and joints (7%).

The study demonstrated treatment with abatacept led to a durable reduction in prednisone dose in responders compared with nonresponders, beginning after dose 3 and continuing through the 1 month of follow-up after completion of therapy.

Abatacept was well tolerated overall. The most common adverse events were neutropenia, fatigue, headache, and upper respiratory infection. While on study, 4 patients died, 1 related to abatacept with 1 grade 4 hepatic and respiratory failure secondary to concurrent herpes simplex virus hepatitis and 3 unrelated to abatacept, 1 cardiac arrest, 1 respiratory failure related to pulmonary GVHD, and 1 progression of cGVHD with mesenteric ischemia.

“Abatacept may be a promising alternative agent in settings in which the currently approved drugs are not tolerated because of their side effect profile or lack of efficacy,” concluded the researchers.

Limitations of the study included the small sample size and continued use of other immunosuppressive agents during the trial, including calcineurin inhibitors, corticosteroids, and ruxolitinib.

Disclosure: This research was supported by Bristol-Myers Squibb. Please see the original reference for a full list of disclosures.


Koshy AG, Kim HT, Liegel J, et al. Phase 2 clinical trial evaluating abatacept in patients with steroid-refractory chronic graft-versus-host disease. Blood. 2023;141(24):2932-2943. doi:10.1182/blood.2022019107