A phase 1 trial of itacitinib, a selective JAK1 inhibitor, in patients with acute graft-versus-host disease

Mark A. Schroeder, H. Jean Khoury, Madan Jagasia, Haris Ali, Gary J. Schiller, Karl Staser, Jaebok Choi, Leah Gehrs, Michael C. Arbushites, Ying Yan, Peter Langmuir, Nithya Srinivas, Michael Pratta, Miguel Angel Perales, Yi Bin Chen, Gabrielle Meyers, John F. DiPersio

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57 Scopus citations


Acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic cell transplantation (HCT) is a primary cause of nonrelapse mortality and a major barrier to successful transplant outcomes. Itacitinib is a Janus kinase (JAK)1–selective inhibitor that has demonstrated efficacy in preclinical models of aGVHD. We report results from the first registered study of a JAK inhibitor in patients with aGVHD. This was an open-label phase 1 study enrolling patients aged $18 years with first HCT from any source who developed grade IIB to IVD aGVHD. Patients with steroid-naive or steroid-refractory aGVHD were randomized 1:1 to itacitinib 200 mg or 300 mg once daily plus corticosteroids. The primary endpoint was safety and tolerability; day 28 overall response rate (ORR) was the main secondary endpoint. Twenty-nine patients (200 mg, n 5 14; 300 mg, n 5 15) received $1 dose of itacitinib and were included in safety and efficacy assessments. One dose-limiting toxicity was reported (grade 3 thrombocytopenia attributed to GVHD progression in a patient receiving 300 mg itacitinib with preexisting thrombocytopenia). The most common nonhematologic treatment-emergent adverse event was diarrhea (48.3%, n 5 14); anemia occurred in 11 patients (38%). ORR on day 28 for all patients in the 200-mg and 300-mg groups was 78.6% and 66.7%, respectively. Day 28 ORR was 75.0% for patients with treatment-naive aGVHD and 70.6% in those with steroid-refractory aGVHD. All patients receiving itacitinib decreased corticosteroid use over time. In summary, itacitinib was well tolerated and demonstrated encouraging efficacy in patients with steroid-naive or steroid-refractory aGVHD, warranting continued clinical investigations. This trial was registered at www.clinicaltrials.gov as #NCT02614612.

Original languageEnglish (US)
Pages (from-to)1657-1669
Number of pages13
JournalBlood Advances
Issue number8
StatePublished - Apr 28 2020

ASJC Scopus subject areas

  • Hematology


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