Journal
BLOOD ADVANCES
Volume 4, Issue 8, Pages 1656-1669Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/bloodadvances.2019001043
Keywords
-
Categories
Funding
- Incyte Corporation
- National Institutes of Health, National Cancer Institute [P30-CA9184201, SPORE P50-CA171963-01, R35 1R35-CA210084]
- Amy Strelzer Manasevit Research Program (Be The Match Foundation)
- Amy Strelzer Manasevit Research Program (National Marrow Donor Program)
- Alvin J. Siteman Cancer Center Siteman Investment Program (Foundation for Barnes-Jewish Hospital Cancer Frontier Fund)
- Alvin J. Siteman Cancer Center Siteman Investment Program (National Cancer Institute Cancer Center Support Grant) [P30 CA091842]
- Alvin J. Siteman Cancer Center Siteman Investment Program (Barnard Trust)
Ask authors/readers for more resources
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 = 14; 300 mg, n = 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 = 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available