Ibrutinib interim data promising in patients with chronic graft-versus-host-disease

Ibrutinib may be a safe and potentially effective treatment for patients with chronic graft-versus-host-disease (cGVHD) who were refractory to steroid treatment or steroid-dependent, suggested interim data presented at the 51st American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

There are currently no therapies specifically approved cGVHD, a life-threatening condition in which newly transplanted cells attack the patient's body. Patients may develop this common complication after undergoing allogenic stem cell or bone marrow transplantation.

“Patients with cGVHD are often treated with prednisone or other immunosuppressive therapies, which many patients find difficult to tolerate,” said Danelle James, MD, MS, head of oncology at Pharmacyclics. “The potential of a nonsteroidal option such as ibrutinib is an important leap forward for this very difficult-to-treat post-transplant complication. There is a large unmet need for safe, effective and well-tolerated therapies among this particular patient population.”

The ongoing phase 1b/2 study evaluated the safety and efficacy of ibrutinib (Imburvica, Pharmacyclics and Janssen Biotech) for the treatment of patients with steroid-dependent or refractory cGVHD. The phase 1b portion of the study was open-label and designed to determine the recommended phase 2 dose of ibrutinib, starting at 420 mg. Six patients (median age 56 years, median Karnofsky score 85) were enrolled in the phase 1b portion. The median time from transplant was 23 months and the median time on ibrutinib was 19.3 weeks. The phase 2 study is currently ongoing.

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All 5 evaluable patients who had received at least 3 months of ibrutinib achieved a partial response (PR); 2 patients who were evaluable at 6 months maintained a PR.

Improvements in clinician-assessed GVHD-score, skin erythema and mouth score were observed in patients during the initial analysis. The most common treatment-emergent adverse events (AEs) in this study included fatigue (n=5), diarrhea (n=4), ecchymosis or bruising (n=3) and stomatitis (n=2), all of which were Grade 1 or 2. Serious AEs (SAEs) occurred in 2 patients and included Grade 3 pneumonia, as well as pyrexia and fungal brain abscess; the latter was the only event leading to ibrutinib discontinuation, which occurred at 10.9 weeks. No dose-limiting toxicities were reported in phase 1b.

“Overall, ibrutinib showed early clinical activity in the reduction of cGVHD based on the NIH consensus cGVHD Activity Assessment,” said Dr James.

As a result of the preliminary evaluation of the available data, researchers determined the phase 2 dose of ibrutinib to be 420 mg.

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