Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial

Madan Jagasia, Miguel Angel Perales, Mark A. Schroeder, Haris Ali, Nirav N. Shah, Yi Bin Chen, Salman Fazal, Fitzroy W. Dawkins, Michael C. Arbushites, Chuan Tian, Laura Connelly-Smith, Michael D. Howell, H. Jean Khoury

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Patients who develop steroid-refractory acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation have poor prognosis, highlighting an unmet therapeutic need. In this open-label phase 2 study (ClinicalTrials.gov identifier: NCT02953678), patients aged at least 12 years with grades II to IV steroid-refractory aGVHD were eligible to receive ruxolitinib orally, starting at 5 mg twice daily plus corticosteroids, until treatment failure, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) at day 28; the key secondary end point was duration of response (DOR) at 6 months. As of 2 July 2018, 71 patients received at least 1 dose of ruxolitinib. Forty-eight of those patients (67.6%) had grade III/IV aGVHD at enrollment. At day 28, 39 patients (54.9%; 95% confidence interval, 42.7%-66.8%) had an overall response, including 19 (26.8%) with complete responses. Best ORR at any time was 73.2% (complete response, 56.3%). Responses were observed across skin (61.1%), upper (45.5%) and lower (46.0%) gastrointestinal tract, and liver (26.7%). Median DOR was 345 days. Overall survival estimate at 6 months was 51.0%. At day 28, 24 (55.8%) of 43 patients receiving ruxolitinib and corticosteroids had a 50% or greater corticosteroid dose reduction from baseline. The most common treatment-emergent adverse events were anemia (64.8%), thrombocytopenia (62.0%), hypokalemia (49.3%), neutropenia (47.9%), and peripheral edema (45.1%). Ruxolitinib produced durable responses and encouraging survival compared with historical data in patients with steroid-refractory aGVHD who otherwise have dismal outcomes. The safety profile was consistent with expectations for ruxolitinib and this patient population.

Original languageEnglish
Pages (from-to)1739-1749
Number of pages11
JournalBlood
Volume135
Issue number20
DOIs
StatePublished - May 14 2020
Externally publishedYes

Fingerprint Dive into the research topics of 'Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial'. Together they form a unique fingerprint.

  • Cite this

    Jagasia, M., Perales, M. A., Schroeder, M. A., Ali, H., Shah, N. N., Chen, Y. B., Fazal, S., Dawkins, F. W., Arbushites, M. C., Tian, C., Connelly-Smith, L., Howell, M. D., & Khoury, H. J. (2020). Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial. Blood, 135(20), 1739-1749. https://doi.org/10.1182/blood.2020004823