On August 24, the U.S. Food and Drug Administration (FDA) approved ibrutinib (Imbruvica) for pediatric patients aged at least 1 year with chronic graft-vs-host disease after failure of one or more lines of systemic therapy. Formulations include capsules, tablets, and oral suspension.
Efficacy was evaluated in iMAGINE (ClinicalTrials.gov identifier NCT03790332), an open-label, multicenter, single-arm trial of ibrutinib for pediatric and young adult patients aged 1 year to up to 22 with moderate or severe chronic graft-vs-host disease. The trial included 47 patients who required additional therapy after failure of one or more lines of systemic therapy. Patients were excluded if single-organ genitourinary involvement was the sole manifestation of chronic graft-vs-host disease.
The median age of patients was 13 years (range = 1–19 years). Selected demographics of the 47 patients follow: 70% male, 36% White, 9% Black, and 55% other or unreported race. The main efficacy outcome measure was overall response rate through week 25. Overall response rate included complete response or partial responses according to the 2014 NIH Consensus Development Project Response Criteria.
The overall response rate by week 25 was 60% (95% confidence interval [CI] = 44%–74%). The median duration of response was 5.3 months (95% CI = 2.8–8.8 months). The median time from first response to death or new systemic therapies for chronic graft-vs-host disease was 14.8 months (95% CI = 4.6 months to not evaluable).
The most common adverse reactions, including laboratory abnormalities, occurring in at least 20% of patients were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache.
The recommended dosage of ibrutinib for patients 12 years of age and older with chronic graft-vs-host disease is 420 mg orally once daily, and for patients aged 1 year to up to 12 with chronic graft-vs-host disease, the recommended dose is 240 mg/m2 orally once daily (up to a dose of 420 mg), until chronic graft-vs-host disease progression, recurrence of an underlying malignancy, or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The applications for this action were granted Priority Review; ibrutinib was also granted Orphan Drug designation. The applications were submitted in response to a pediatric Written Request issued by the FDA.