Among patients with low-risk, acute graft vs host disease (GVHD), itacitinib monotherapy may be as effective, with a lower risk of serious infection, as are systemic corticosteroids (SCSs), according to research published in Blood.

SCSs comprise the mainstay treatment of low-risk, acute GVHD among patients who undergo allogenic transplantation that develop it. SCSs are, however, associated with a large number of morbidities, including a risk of serious infection, such as sepsis and invasive fungal infection. Patients frequently also continue treatment even after GVHD symptoms resolve, raising infection risk.

Itacitinib is a monoclonal antibody that selectively inhibits JAK1. In previous studies, furthermore, there has been evidence that the risk of hematologic toxicities is lower with itacitinib than that seen with ruxolitinib, a JAK1/2 inhibitor approved by the US Food and Drug Administration for the treatment of acute GVHD resistant to SCS therapy.

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For this phase 2 study ( Identifier: NCT03846479), researchers evaluated whether itacitinib monotherapy yields non-inferior safety and efficacy outcomes to SCSs among patients who develop acute, low-risk GVHD. The authors evaluated itacitinib safety and activity in a cohort of enrolled patients and compared results with data from a control cohort of individuals treated with SCSs.

Overall, 70 patients were enrolled to the experimental arm of this trial. All patients received at least 1 28-day cycle of itacitinib 200 mg/day. The matched control cohort consisted of 140 patients.

Analysis suggested that, compared with SCSs, patients who received itacitinib were more likely to respond to treatment within 7 days of initiating therapy (81% vs 66%; P =.02). Response rates were, however, similar at 28 days between the 2 groups (89% with itacitinib vs 86% with SCSs; P =.67).

Critically, serious infection within 90 days was less common among patients treated with itacitinib (27% vs 42% with SCSs; P =.04).

Further analysis suggested that there was no difference between the 2 groups in nonrelapse mortality rates, relapse rates, chronic GVHF rates, or overall survival rates.

The only grade 3 or worse adverse event noted in more than 10% of patients treated with itacitinib was severe leukopenia (16%), which occurred less frequently in the experimental cohort than in the control cohort (31%; P =.02).

“Patients with low risk GVHD are ideal for testing strategies that de-escalate treatment intensity, either by replacing SCS with less toxic drugs, shorter SCS courses, or both,” the authors wrote in their report. “A randomized trial of itacitinib vs SCS is necessary to expand and validate these findings and to determine the benefits of a SCS-free approach to GVHD treatment.”

Disclosure: Thestudy author(s) declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 


Etra AM, Capellini A, Alousi AM, et al. Effective treatment of low risk acute GVHD with itacitinib monotherapy. Blood. Published online September 12, 2022. doi:10.1182/blood.2022017442