Ibrutinib for chronic graft-versus-host disease after failure of prior therapy

David Miklos, Corey S. Cutler, Mukta Arora, Edmund K. Waller, Madan Jagasia, Iskra Pusic, Mary E. Flowers, Aaron C. Logan, Ryotaro Nakamura, Bruce R. Blazar, Yunfeng Li, Stephen Chang, Indu Lal, Jason Dubovsky, Danelle F. James, Lori Styles, Samantha Jaglowski

Research output: Contribution to journalArticlepeer-review

235 Scopus citations


Chronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic stem cell transplantation with few effective options available after failure of corticosteroids. B and T cells play a role in the pathophysiology of cGVHD. Ibrutinib inhibits Bruton tyrosine kinase in B cells and interleukin-2–inducible T-cell kinase in T cells. In preclinical models, ibrutinib reduced severity of cGVHD. This multicenter, open-label study evaluated the safety and efficacy of ibrutinib in patients with active cGVHD with inadequate response to corticosteroid-containing therapies. Forty-two patients who had failed 1 to 3 prior treatments received ibrutinib (420 mg) daily until cGVHD progression. The primary efficacy end point was cGVHD response based on 2005 National Institutes of Health criteria. At a median follow-up of 13.9 months, best overall response was 67%; 71% of responders showed a sustained response for ‡20 weeks. Responses were observed across involved organs evaluated. Most patients with multiple cGVHD organ involvement had a multiorgan response. Median corticosteroid dose in responders decreased from 0.29 mg/kg per day at baseline to 0.12 mg/kg per day at week 49; 5 responders discontinued corticosteroids. The most common adverse events were fatigue, diarrhea, muscle spasms, nausea, and bruising. Plasma levels of soluble factors associated with inflammation, fibrosis, and cGVHD significantly decreased over time with ibrutinib. Ibrutinib resulted in clinically meaningful responses with acceptable safety in patients with ‡1 prior treatments for cGVHD. Based on these results, ibrutinib was approved in the United States for treatment of adult patients with cGVHD after failure of 1 or more lines of systemic therapy. This trial was registered at www.clinicaltrials.gov as #NCT02195869.

Original languageEnglish
Pages (from-to)2243-2250
Number of pages8
Issue number21
StatePublished - Nov 23 2017


Dive into the research topics of 'Ibrutinib for chronic graft-versus-host disease after failure of prior therapy'. Together they form a unique fingerprint.

Cite this