Ibrutinib Approved for Pediatric Patients With Chronic Graft-Versus-Host Disease

Colonic crypts showing foci of apoptotic nuclear debris, a feature of graft-versus-host disease.

The FDA has approved ibrutinib (Imbruvica^®, Pharmacyclics LLC) for treatment of pediatric patients with chronic graft-versus-host disease (cGVHD) following failure of one or more lines of systemic therapy.

"Pediatric cGVHD, a potentially debilitating, life-threatening complication of allogeneic hematopoietic stem cell transplantation, has limited treatment options," wrote Marco Zecca, MD, Director of the Pediatric Oncology/Hematology Unit at the Fondazione IRCCS Policlinico San Matteo in Italy, and colleagues, in their presentation of the results of the iMAGINE study (NCT03790332) at the EBMT 48^th Annual Meeting. "Ibrutinib, a once-daily oral Bruton's tyrosine kinase inhibitor, is the first approved therapy in the United States for adults with cGVHD after failure of prior systemic therapy."

Safety and efficacy were measured in the phase 1/2, open-label, single-arm trial, which enrolled 47 pediatric patients, ages 1 to 22, with moderate-to-severe cGVHD who required additional treatment following one or more lines of systemic therapy. Each patient was given ibrutinib once daily by capsule, tablet, or oral suspension. The trial was split in two parts, Part A and Part B. In Part A, the recommended pediatric equivalent dosage (RPED) was measured, and if patients participated in Part B, their dosage was adjusted to their corresponding RPED. Patients 12 years and older received 420 mg of ibrutinib once daily, and patients 12 and younger received 240 mg/m² once daily.

The primary end point studied was overall response rate, including partial and complete response according to the 2014 National Institutes of Health (NIH) Consensus Development Project Response Criteria, with a key secondary end point of duration of response. Overall response rate was recorded to be 60% at Week 25, with a median duration of response of 5.3 months.

The most common adverse events in ≥20% of patients, including laboratory abnormalities, were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache.

"In this analysis of children with previously untreated and relapsed/refractory moderate/severe cGVHD, pharmacokinetics and safety were consistent with the known profiles for ibrutinib and cGVHD," concluded Dr. Zecca and colleagues. "Response rates were higher than previously observed in adults and were generally durable, demonstrating promising activity of ibrutinib in children with GVHD."

The recommended dosage of ibrutinib for pediatric patients with cGVHD who are 12 years and older is 420 mg orally once daily, and for patients 12 years and younger, is 240 mg/m² orally once daily until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity.

For More Information

Zecca M, Carpenter PA, Kang HJ, et al (2022). Prospective trial of ibrutinib for the treatment of pediatric chronic graft-versus-host disease [oral presentation]. EBMT 48^th Annual Meeting. Abstract OS10.

Clinicaltrials.gov (2022). Phase 1/2 dose finding and safety study of ibrutinib in pediatric subjects with chronic graft versus host disease (cGVHD). NLM identifier: NCT03790332.

Imbruvica^® (ibrutinib) prescribing information (2022). Pharmacyclics LLC. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/217003s000lbl.pdf

US Food and Drug Administration (2022). FDA approves ibrutinib for pediatric patients with chronic graft versus host disease, including a new oral suspension. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ibrutinib-pediatric-patients-chronic-graft-versus-host-disease-including-new-oral

Image credit: Mark ong. Licensed under CC BY-SA 4.0