FDA Approves Ibrutinib for Previously Treated Peds and Young Adults With cGVHD

Findings from.the phase 1/2 IMAGINE have led the FDA to approve ibrutinib for select pediatric and young adult patients with chronic graft-versus-host disease.

The FDA has granted approval to ibrutinib (Imbruvica) for the treatment of pediatric patients ≥ 1 year of age with chronic graft versus host disease (cGVHD) who failed 1 or more lines of systemic therapy. Ibrutinib is available for this indication as a capsule, tablet, and oral suspension.1

Approval was granted based on findings from the phase ½ IMAGINE clinical trial (NCT03790332). The study showed activity through a positive objective response rate and response durability.

In 47 pediatric patients with cGVHD, the ORR at week 25 was 60% (95% CI: 44-74). The median duration of response observed was 5.3 months (95% CI: 2.8- 8.8). The study also showed a median time from first response to death or new systemic therapies for cGVHD of 14.8 months (95% CI: 4.6 to not evaluable).1

For safety, the most common adverse events were anemia, musculoskeletal pain, pyrexia, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache. Common AEs occurred in ≥ 20% of patients in the study.

IMAGINE was an open-label, multi-center, single-arm trial of ibrutinib administered to pediatric and young adult patients with moderate or severe cGVHD. Baseline characteristics showed that patients had a median age of 13 years (range, 1-19). The population was 70% male, 36% White, 9% Black or African American, and 55% other or unreported.2

In the IMAGINE trial, patients with moderate to severe cGVHD aged 1-22 with a Karnofsky or Lansky performance score of ≥ 60 are treated with ibrutinib 120 mg/m2 once daily during phase 1, which is escalated to 240 mg/m2 after 14 days in patients without grade 3 toxicity to determine the recommended phase 2 dose of the agent. The coprimary end points of the study are PK, and safety/tolerability determined by the number of patients with AEs. As secondary end points, the study is investigating safety/tolerability, response rate at week 24, duration of response, overall survival, late effects surveillance, and laboratory parameters.2

According to the FDA, the recommended dosage of ibrutinib for patients 12 years of age and older with cGVHD is 420 mg orally once daily. For patients who are 1 year old to younger than 12 years old with cGVHD, the recommended dosage is 240 mg/m2 orally once daily. Ibrutinib can be administered until cGVHD progression, recurrence of an underlying malignancy, or unacceptable toxicity.1

“The pediatric cGVHD community is a prime example of an underserved patient population with high unmet medical needs for whom Janssen is committed to developing life-saving therapies,” said Craig Tendler, MD, global head of Late Development, Diagnostics & Medical Affairs, Hematology & Oncology Janssen Research & Development, LLC, in a press release.3 “cGVHD has life-threatening implications for children, and we are deeply proud of the opportunity to make an impact for these young patients with Imbruvica and their families.”


1. FDA approves ibrutinib for pediatric patients with chronic graft versus host disease, including a new oral suspension. News release. FDA webstie. Accessed August 24, 2022. https://bit.ly/3CoNsMy

2. Phase 1/2 dose finding and safety study of ibrutinib in pediatric subjects with chronic graft versus host disease (cGVHD). Clinicaltrials.gov. Accessed February 28, 2022. https://bit.ly/3K9GfAJ

3. U.S. FDA approves Imbruvica® (ibrutinib) as first and only BTKi treatment for pediatric patients with chronic graft-versus-host disease. News release. The Janssen Pharmaceutical Companies of Johnson & Johnson. August 24, 2022. Accessed August 24, 2022. https://bit.ly/3QWiLms