Using the tyrosine kinase inhibitor ibrutinib to treat steroid-resistant chronic graft-versus-host disease (GVHD) can result in overall response rates of 67%, according to results of a multicenter, open-label phase 2 study of 42 transplant recipients.
Researchers examined ibrutinib in transplant recipients who had received 1-3 prior regimens for chronic GVHD and had either >25% body surface area erythematous rash or a National Institutes of Health (NIH) mouth score >4. Patients were treated with daily ibrutinib (420 mg) until chronic GVHD progression or unacceptable toxicity.
Median age of patients was 56 years (range, 19-74) and median duration of chronic GVHD before study entry was 13.7 months (range, 1.1-63.2).
At a median follow up of 13.9 months, overall 28 of 42 patients (67%) responded including 9 (21%) complete responses and 19 (45%) partial response. Of the 28 responders, 20 (71%) had a sustained response of ≥20 weeks.
Most patients with multiple chronic GVHD organ involvement had a multi-organ 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. Five responders discontinued corticosteroids.
There were 7 deaths during the study, and 14 patients discontinued ibrutinib therapy for adverse events including fatigue (n=3) and pneumonia (n=2).
Lead researcher Dr. David Miklos of Stanford University reported that the observed response rates in this pre-treated, high-risk population supported the approval of ibrutinib for treatment of adult patients with chronic GVHD after failure of ≥1 lines of systemic therapy. He concluded that further validation is necessary, and noted that a randomized phase 3 trial of frontline administration of ibrutinib is underway (NCT02959944).