Phase I/II Study of Baricitinib in Refractory cGVHD
Vs-Host-Disease: Results of a Phase 1/2 Study. Blood Advances. 2026; (doi: 10.1182/bloodadvances.2025018898).
Researchers report that further study is warranted after baricitinib achieved significant durable response in a small sample of patients with refractory severe chronic graft-versus-host disease (cGVHD) following allogeneic hematopoietic cell transplantation. JAK-STAT targeting is a known and effective therapeutic pathway for cGVHD, but currently available options have been challenged by toxicities and short durations of response. In a single-site, Phase I/II investigation that included 24 adults who did not respond adequately to two or more prior lines of therapy, baricitinib demonstrated promising results. The JAK 1/2 inhibitor was administered at 2 mg and 4 mg daily and was well tolerated, with no dose-limiting toxicities observed for either dosage. The overall response rate was 76.2% at 6 months, the median failure-free survival was 19 months, and no deaths or malignancy relapse were observed. The researchers recommend earlier-line and larger-scale trials of baricitinib, which they report works by curbing cytokine-induced signaling (pSTAT) in CD4+ and CD8+ T cells and by reducing circulating proinflammatory cytokines implicated in cGVHD pathophysiology.