At the 64th ASH Annual Meeting and Exposition, researchers presented early findings from the dose-finding portion of GRAVITAS-309, a study on itacitinib combined with corticosteroids as first-line treatment for patients with moderate or severe chronic graft-versus-host disease (GVHD).
Lead author and presenter, Annie Im, MD, said the preliminary results showed increased rates of overall and complete response with itacitinib and corticosteroids compared with corticosteroids alone; however, the combined regimen also increased rates of cytopenia, infection, and mortality.
Not Enough Benefit With Itacitinib Plus Corticosteroid in cGVHD
The first portion of the study enrolled 11 and 10 patients to receive itacitinib at a dose of 200 mg or 300 mg once daily, respectively, alongside corticosteroids. Researchers then expanded to itacitinib 400 mg or 300 mg twice daily groups and a corticosteroid monotherapy control group. The primary end point was identifying a recommended itacitinib schedule for further research.
At the data cutoff of January 31, 2022, 103 patients had been enrolled and received at least 1 dose of itacitinib. The median duration of treatment was 27-28 weeks of itacitinib with 13-16 weeks of concurrent corticosteroid in the combination groups, and 17 weeks in the corticosteroid monotherapy group.
Notably, the itacitinib 300 mg twice a day group was discontinued early due to relapse of underlying malignancy in 4 of 29 patients (14%) and because a higher proportion of subjects required dose reductions compared with the 400 and 300 mg once a day groups. The incidence of grade 3 or higher treatment-emergent adverse events was higher in all itacitinib cohorts than in the corticosteroid group (65% vs 31%).
Cytomegalovirus infections were reported in 10%-15% of patients in the itacitinib cohorts compared with 3% in the corticosteroid cohort. Finally, the rate of all-cause mortality in the itacitinib cohorts ranged from 14% to 18% compared with 11% in the monotherapy group, with infections as the most common cause.
Ultimately, the authors suggested that “this benefit:risk ratio does not support moving the combination of itacitinib [plus corticosteroids] to a later phase of development in first-line therapy of chronic GVHD.”
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