The JAK inhibitor itacitinib demonstrated similar efficacy with fewer serious infections compared with corticosteroids for the treatment of low-risk, acute graft vs host disease (GVHD), according to the results of a study published Blood.

The standard of care for the treatment of acute GVHD is systemic corticosteroids. Because the treatment duration is typically months, corticosteroids can result in serious bacterial, viral, and fungal infections. The aim of this study was to determine if a JAK inhibitor with low risk of causing myelosuppression and cytopenias could provide similar efficacy as corticosteroids but an improved safety profile.

This multicenter, phase 2 trial treated 70 patients with low-risk GVHD after undergoing a bone marrow transplant with itacitinib for 1 cycle of 28 days, with responding patients allowed to continue to a second cycle. At the end of treatment, itacitinib was discontinued without tapering. Outcomes were compared with a matched control set of 140 patients treated with systemic corticosteroids. The primary endpoint was overall response rate (ORR) at 28 days.

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Response rates were higher at 7 days in the itacitinib group at 81% compared with 66% in the corticosteroid group (P =.02). The ORR at 28 days was 89% and 86% with itacitinib and corticosteroids, respectively (P =.67). The ORR was similar between groups for all subgroups evaluated, including different grades of GVHD, target organ involvement, patient age, conditioning regimen, stem cell source, and GVHD prophylaxis.

The occurrence of symptomatic flares was similar between the groups at 11% and 12%, respectively (P =.88). At 1 year, the rates of nonrelapse mortality (P =.21), relapse (P =.64), chronic GVHD (P =.33), and overall survival (P =.11) were similar between the groups.

Infectious complications occurred less frequently in the itacitinib group. Patients treated with itacitinib demonstrated a significantly lower cumulative incidence of serious infections at 90 days compared with patients treated with corticosteroids. The itacitinib group also developed significantly fewer infections per patient with a mean of 0.43 compared with 0.66 with corticosteroids (rate ratio, 0.65; 95% CI, 0.43-0.97; P =.04). Severe infections were significantly less likely to occur in the itacitinib group compared with the corticosteroid group (odds ratio, 0.50; 95% CI, 0.27-0.93).

Grade 3-4 cytopenia developed among 37% and 49% of patients treated with itacitinib or corticosteroids, respectively (P =.11). Of the cytopenias, leukopenia occurred significantly less frequently in the itacitinib group at 16% compared with 31% in the corticosteroid group (P =.02).

There were 30% of patients who developed grade 3 or higher nonhematologic treatment-emergent adverse events, with the most common being alanine aminotransferase elevation and hypertension.

The authors noted that “our findings must be interpreted cautiously, however, because the 2 groups were not randomized and we did not control for numerous other host and donor factors that may contribute to the risk of hematologic toxicities or infections.” They concluded that “itacitinib monotherapy seems to be a safe and effective alternative to systemic corticosteroid treatment for low-risk GVHD and deserves further investigation.”

Disclosures: This study was supported in part by Incyte. Please see the original reference for a full list of disclosures.


Etra A, Capellini A, Alousi A, et al. Effective treatment of low-risk acute GVHD with itacitinib monotherapy. Blood. 2023;141:481-489. doi: 10.1182/blood.2022017442