- Partial response to ibrutinib for chronic graft vs host disease (cGVHD) in pediatric hematopoietic cell transplantation (HCT) recipients suggests its use as salvage therapy.
Why this matters
- cGVHD is a leading cause of late nonrelapse mortality after HCT.
- No second-line treatment for children exists after steroids, which have high toxicity with long-term use.
- Retrospective review of ibrutinib use for cGVHD at Cincinnati Children’s Hospital Medical Center: 12 patients (median, 11 years; range, 3-19 years) with cGVHD (8 severe, 1 moderate, 3 mild) received 250 mg/m2 orally once daily from August 2017 to October 2018.
- Patients had steroid-dependent (n=2) or -refractory (n=10) cGVHD.
- Dose halved for concomitant CYP3A4 inhibitor.
- Median dose 140 mg (70-420 mg).
- Median duration 170.5 days (28-341 days).
- Diagnoses: malignancy (46%), primary immune deficiency (15%), and hemoglobinopathies (30%).
- Stem cell sources: bone marrow (59%), cord blood (16%), and peripheral blood (25%).
- 8 of 8 evaluable patients at 6 months achieved partial response; 4 discontinued (death/adverse events).
- Of 6 patients with lung involvement, 1 recovered lung function, 1 improved, and 2 were stable.
- 1 patient discontinued steroids, 2 weaned to physiologic steroids, and 5 weaned to 50% of pre-ibrutinib dose.
- Following ibrutinib initiation, levels of plasma IL-6 (n=7) and CXCL9 (n=5) declined.
- Adverse events: 3 thrombocytopenia, 2 neutropenia, 1 pneumococcal sepsis, 1 Epstein-Barr virus activation.