On August 24, 2022, ibrutinib was approved for pediatric patients 1 year of age or older with chronic graft-vs-host disease after failure of one or more lines of systemic therapy.1 A new oral suspension formulation is available.
Supporting Efficacy Data
Approval was based on findings from the multicenter iMAGINE trial (ClinicalTrials.gov identifier NCT03790332), which enrolled patients aged 1 to 22 years with moderate or severe chronic graft-vs-host disease who required additional therapy after failure of one or more lines of systemic therapy. A total of 47 patients (median age = 13 years, range = 1–19 years) received oral ibrutinib at doses of 420 mg once daily for those aged 12 years and older and 240 mg/m2 once daily for those aged 1 to 12 years.
By week 25, a total of 28 patients (60%, 95% confidence interval [CI] = 44%–74%) had a complete (n = 2) or partial response, according to 2014 National Institutes of Health Consensus Development Project Response Criteria. 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 therapy for chronic graft-vs-host disease was 14.8 months (95% CI = 4.6 months to not evaluable).
How It Is Used
The recommended dosage of ibrutinib is 420 mg once daily for patients aged 12 years or older and 240 mg/m2 once daily (up to 420 mg) for those aged 1 to 12 years and older, with treatment continued until chronic graft-vs-host disease progression, recurrence of underlying malignancy, or unacceptable toxicity.
Product labeling provides instructions on dosage modification for adverse reactions including cardiac toxicity, other grade 3 or 4 nonhematologic toxicity, and hematologic toxicity; hepatic impairment; and concomitant use with moderate or strong CYP3A inhibitors. Concomitant use of ibrutinib with strong CYP3A inducers (eg, rifampin, phenobarbital, phenytoin) should be avoided.
Among the 47 patients in the iMAGINE trial, the most common (≥ 20%) adverse events of any-grade reactions, including laboratory abnormalities, were anemia (49%), musculoskeletal pain (30%), pyrexia (30%), diarrhea (28%), pneumonia (23%), abdominal pain (23%), stomatitis (23%), thrombocytopenia (21%), and headache (21%). The most common grade 3 or 4 adverse events included pneumonia (13%), pyrexia (11%), and osteonecrosis, stomatitis, and sepsis (9% each).
Serious adverse events were reported in 64% of patients; those occurring in more than two patients were pneumonia, pyrexia, sepsis, and stomatitis. Adverse events led to discontinuation of treatment in 23%; fatal adverse events occurred in two patients.
Ibrutinib has warnings/precautions for hemorrhage; infections; cytopenias; cardiac arrhythmia, cardiac failure, and sudden death; hypertension; second primary malignancies; tumor-lysis syndrome; and embryofetal toxicity. Patients should be advised not to breastfeed while receiving ibrutinib.
1. Imbruvica (ibrutinib) capsules, tablets, and oral suspension prescribing information, Pharmacyclics LLC, Janssen Biotech, Inc, August 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/217003s000lbl.pdf. Accessed August 30, 2022.