Effective treatment of low-risk acute GVHD with itacitinib monotherapy

• Published in: Blood Vol. 141; no. 5; pp. 481 - 489
• Main Authors: Etra, Aaron, Capellini, Alexandra, Alousi, Amin, Al Malki, Monzr M., Choe, Hannah, DeFilipp, Zachariah, Hogan, William J., Kitko, Carrie L., Ayuk, Francis, Baez, Janna, Gandhi, Isha, Kasikis, Stelios, Gleich, Sigrun, Hexner, Elizabeth, Hoepting, Matthias, Kapoor, Urvi, Kowalyk, Steven, Kwon, Deukwoo, Langston, Amelia, Mielcarek, Marco, Morales, George, Özbek, Umut, Qayed, Muna, Reshef, Ran, Rösler, Wolf, Spyrou, Nikolaos, Young, Rachel, Chen, Yi-Bin, Ferrara, James L. M., Levine, John E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.02.2023; The American Society of Hematology
• Subjects: Acetonitriles - therapeutic use; Adrenal Cortex Hormones - therapeutic use; Clinical Trials and Observations; Graft vs Host Disease - drug therapy; Graft vs Host Disease - etiology; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Pyrazoles - adverse effects; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2022017442

•Itacitinib monotherapy is as effective as systemic corticosteroids for the treatment of low-risk acute GVHD.•Itacitinib monotherapy resulted in fewer serious infections compared with systemic corticosteroids. [Display omitted] 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. Primary therapy for acute graft vs host disease (aGVHD) is systemic corticosteroids. Etra et al report on the results of a nonrandomized study of monotherapy with the selective JAK1 inhibitor itacitinib in 70 patients with low-risk aGVHD, compared to a contemporaneous cohort of steroid-treated patients. Responses to itacitinib were comparable to steroids (89% vs 86% at 28 days), with fewer serious viral and fungal infections with itacitinib, providing support for a randomized clinical trial in low-risk GVHD.