Sirolimus as add-on therapy to corticosteroids for moderate-severe chronic graft versus host disease.

Introduction: The first-line treatment of moderate-severe chronic graft versus host disease (cGVHD) involves systemic corticosteroids ± calcineurin inhibitors. Around half of the patients will need second-line agents for corticosteroid-refractory/dependent (SR/SD) cGVHD. Herein, we report our experience using sirolimus as an add-on agent to corticosteroids in moderate-severe cGVHD.

Methods: This was a single-center study of allogeneic cell transplant recipients aged ≥ 12 during 2016-2022. The diagnosis and severity of cGVHD were as per the NIH-2014 criteria. At the physician's discretion, sirolimus was added to corticosteroids for moderate to severe cGVHD. The GVHD response was classified based on the EBMT-NIH-CIBMTR criteria.

Results: cGVHD occurred in 66 (49%) out of 134 recipients. It was mild in 13 (10%) and moderate-severe in 53 (39%) recipients. Sirolimus was used in 38 out of 53 (71.6%) patients with moderate-severe cGVHD, with equal proportions of matched-related (53%) and haploidentical HCT (47%) recipients. The median time to onset of cGVHD was 140 days (IQR 108-182). The onset was de novo in 14 (37%), quiescent in 15 (39%), and progressive in 9 (24%) patients. The median duration on sirolimus was 283 days (134-640). cGVHD was controlled in 30 (79%) and active in 8 (21%) recipients at 6 months. Dyslipidemia was the most common (73%) adverse event. Failure-free survival at two years was 61% (95% CI 38-78%).

Discussion: This study demonstrates the safety and efficacy of sirolimus as an add-on agent to systemic corticosteroids in managing moderate-severe cGVHD. This strategy can reduce the burden of SR/SD cGVHD.