A novel Janus kinase 1 and 2 inhibitor, baricitinib, for steroid-refractory chronic graft-versus-host disease after allogeneic stem cell transplantation Free

Introduction Allogeneic stem cell transplantation (allo-SCT) is an effective and straightforward therapy for hematology patients, and chronic graft-versus-host disease (cGVHD) is recognized as a major and important complication of HSCT. cGVHD occurs in approximately 50% of patients who undergo HSCT and affects multiple organs. The standard first-line treatment for cGVHD is systemic glucocorticoids; however, approximately 50% of patients become glucocorticoid refractory or glucocorticoid dependent, which worsens the risk of poor outcomes. The second-line treatment, including methotrexate, mycophenolate mofetil, ibrutinib, and ruxolitinib, varies substantially among different centers. Ruxolitinib, a Janus kinase 1 and 2 (JAK1‒JAK2) inhibitor, is an effective treatment for steroid-refractory chronic GVHD patients after allo-HSCT. The overall response rate was 49.7%, but the most common adverse event was thrombocytopenia, which occurred in 15.2% of the patients. Accordingly, baricitinib, an orally administered, selective and reversible JAK1-JAK2 inhibitor, has the potential to increase platelet levels, and whether it can be applied to cGVHD was the focus of this study.

Methods We performed a retrospective study of patients at 16 years of age or older who received allo-HSCT between January 2024 and February 2025 at our center. In total, 32 patients who received baricitinib as salvage therapy for steroid-refractory or steroid-dependent cGVHD underwent allo-HSCT according to the National Institutes of Health (NIH) consensus criteria. Patients were included in this survey if they were treated with baricitinib for cGVHD that was refractory to steroid treatment or had been given steroids for at least 3 weeks for cGVHD. Patients were ineligible if they had received 2 or more systemic therapies in addition to steroids. Patients were excluded if they had a relapse of the primary cancer or if they had an active, uncontrolled infection. The Cochran–Mantel–Haenszel chi-square test, stratified according to the severity of chronic GVHD, was used to compare overall responses. Efficacy analyses were performed on the full analysis set according to the intention-to-treat principle.

Results A total of 32 patients with cGVHD who underwent allo-HSCT were enrolled. Among them, 16/32 (50.00%) patients had mild cGVHD, 10/32 (31.25%) had moderate cGVHD, and 6/32 (18.75%) had severe cGVHD. Most patients were beyond second-line treatment for cGVHD, with a median number of 3 prior treatments (1-5) before baricitinib. The median time of baricitinib use after HSCT was 226 (112-650) days, and the median time to response was 13 (5-31) days after the initiation of baricitinib treatment. The overall response rate (ORR) was 90.63% (29/32), including 20 (62.50%) patients with a complete response (CR) and 9 (28.13%) with a partial response (PR). In 19/32 (59.37%) patients, more than one organ system was involved. Some patients with symptoms involving the skin, liver, or mouth showed impressive responses, but those with steroid-refractory or steroid-dependent cGVHD involving the lungs or the eyes had a poor response. The median follow-up time was 262 (170–535) days, and the 6-month overall survival rate was 84.2% (95% CI: 74.3–94.1%). One patient died due to a second malignancy, and one died due to severe cGVHD involving the skin, liver and lungs. Infections were observed during baricitinib treatment; among them, 1/32 (3.13%) patients had cytomegalovirus infection, 1/32 had Epstein–Barr virus infection, and 1/32 had severe parvovirus B19 infection. Cytopenia rarely occurred in these patients, and platelet levels increased during baricitinib therapy, whereas adverse thrombotic events, as known side effects, were observed in 2/32 (6.25%) patients, leading to discontinuation of baricitinib treatment.

Conclusions In patients with steroid-refractory or steroid-dependent chronic GVHD after allo-HSCT, baricitinib led to a significant overall response and relatively few adverse events. Moreover, unlike other JAK1‒JAK2 inhibitors, the most important effect of baricitinib is the increase in platelet levels. The evidence from this study suggests that baricitinib might be a novel candidate for treating steroid-refractory or steroid-dependent cGVHD. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with cGVHD after HSCT.