Effective treatment of low-risk acute GVHD with itacitinib monotherapy

Etra A, Capellini A, Alousi A, Al Malki MM, Choe H, DeFilipp Z, Hogan WJ, Kitko CL, Ayuk F, Baez J, Gandhi I, Kasikis S, Gleich S, Hexner E, Hoepting M, Kapoor U, Kowalyk S, Kwon D, Langston A, Mielcarek M, Morales G, Özbek U, Qayed M, Reshef R, Rösler W, Spyrou N, Young R, Chen YB, Ferrara JL, Levine JE (2023)

Publication Type: Journal article

Publication year: 2023


Book Volume: 141

Pages Range: 481-489

Journal Issue: 5

DOI: 10.1182/blood.2022017442


The standard primary treatment for acute graft-versus-host disease (GVHD) requires prolonged, high-dose systemic corticosteroids (SCSs) that delay reconstitution of the immune system. We used validated clinical and biomarker staging criteria to identify a group of patients with low-risk (LR) GVHD that is very likely to respond to SCS. We hypothesized that itacitinib, a selective JAK1 inhibitor, would effectively treat LR GVHD without SCS. We treated 70 patients with LR GVHD in a multicenter, phase 2 trial (NCT03846479) with 28 days of itacitinib 200 mg/d (responders could receive a second 28-day cycle), and we compared their outcomes to those of 140 contemporaneous, matched control patients treated with SCSs. More patients responded to itacitinib within 7 days (81% vs 66%, P = .02), and response rates at day 28 were very high for both groups (89% vs 86%, P = .67), with few symptomatic flares (11% vs 12%, P = .88). Fewer itacitinib-treated patients developed a serious infection within 90 days (27% vs 42%, P = .04) due to fewer viral and fungal infections. Grade ≥3 cytopenias were similar between groups except for less severe leukopenia with itacitinib (16% vs 31%, P = .02). No other grade ≥3 adverse events occurred in >10% of itacitinib-treated patients. There were no significant differences between groups at 1 year for nonrelapse mortality (4% vs 11%, P = .21), relapse (18% vs 21%, P = .64), chronic GVHD (28% vs 33%, P = .33), or survival (88% vs 80%, P = .11). Itacitinib monotherapy seems to be a safe and effective alternative to SCS treatment for LR GVHD and deserves further investigation.

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Etra, A., Capellini, A., Alousi, A., Al Malki, M.M., Choe, H., DeFilipp, Z.,... Levine, J.E. (2023). Effective treatment of low-risk acute GVHD with itacitinib monotherapy. Blood, 141(5), 481-489. https://doi.org/10.1182/blood.2022017442


Etra, Aaron, et al. "Effective treatment of low-risk acute GVHD with itacitinib monotherapy." Blood 141.5 (2023): 481-489.

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