On August 24, 2022, the U.S. Food and Drug Administration (FDA) approved ibrutinib (Imbruvica®) for pediatric patients aged less than 1 year with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy. Formulations include capsules, tablets, and oral suspension.
Efficacy was evaluated in iMAGINE (NCT03790332), an open-label, multicenter, single-arm trial of ibrutinib for pediatric and young adult patients aged 1 to less than 22 years with moderate or severe cGVHD. The trial included 47 patients who required additional therapy after failure of one or more lines of systemic therapy. Patients whose cGVHD manifested only as single-organ genitourinary involvement were excluded.
The study patients’ median age was 13 years (range = 1–19), and 70% were male, 36% White, 9% Black or African American, and 55% other or unreported.
The main efficacy outcome measure was overall response rate (ORR) through week 25. ORR included complete response or partial responses according to the 2014 National Institutes of Health Consensus Development Project Response Criteria. ORR by week 25 was 60% (95% CI = 44, 74). The median duration of response was 5.3 months (95% CI = 2.8, 8.8). The median time from first response to death or new systemic therapies for cGVHD was 14.8 months (95% CI = 4.6, not evaluable).
The most common adverse reactions reported in at least 20% of patients in the study’s clinical trial were laboratory abnormalities, anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache.
The recommended ibrutinib dosage is 420 mg orally once daily for patients aged 12 years and older and 240 mg/m2 orally once daily (up to a dose of 420 mg) for patients aged 1 to less than 12 years until patients experience cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity.
View the full prescribing information for ibrutinib.
The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.
The applications for this action were granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics. Ibrutinib also was granted orphan drug designation. The applications were submitted in response to FDA’s pediatric written request.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.