Ibrutinib in Pediatric Patients With Chronic GVHD

By Patrick Daly - Last Updated: September 15, 2022

In the phase 1/2 iMAGINE study, Paul Carpenter, MBBS, and colleagues evaluated ibrutinib in the treatment of pediatric patients with chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation. Their article, published in Transplantation and Cellular Therapy, reported that ibrutinib yielded durable responses in this population at a numerically higher rate than previously shown in adult patients.

The study enrolled 59 patients with a median age of 13 years (range, 1-19), of which 12 were treatment-naïve and 47 were relapsed or refractory to previous treatment. The primary end point of the study was identifying the recommended pediatric equivalent dose (RPED), while secondary end points included overall response rate (ORR), overall survival, and duration of response (DOR).

Participants 12 years or younger were administered ibrutinib 120 mg/m2 once daily, escalating to 240 mg/m2 after 14 days if no treatment-related grade 3 or higher toxicities were reported. Patients 12 years or older received ibrutinib 420 mg once daily.

According to the researchers, plasma concentration-time profiles for ibrutinib 240 mg/m2 in pediatric patients were comparable to those reported in adults with once-daily 420 mg, and 240 mg/m2 was established as the RPED. The authors also noted that safety was consistent with published evidence on ibrutinib.

Regarding secondary outcomes, the 24-week ORR was 64% overall, 83% for the treatment-naïve patients, and 60% for the relapsed or refractory patients. In the 46 responders with a median follow-up of 20 months (range, 2-32), the DOR was 60% for treatment-naïve (95% CI, 25-83) and 58% (95% CI, 35-75) for relapsed or refractory. The researchers also reported improvements in quality-of-life outcomes.

Given their findings, Carpenter and colleagues concluded that “ibrutinib may represent a new, effective therapeutic option for children with moderate or severe cGVHD.”

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