Ibrutinib for the treatment of chronic graft-vs-host disease in pediatric hematopoietic stem cell transplant patients: A single-center experience.

Abstract

cGVHD is a significant cause of morbidity and mortality after transplant. Ibrutinib has been studied as treatment for cGVHD in the adult population. Pediatric dosing and safety of ibrutinib are unknown. We conducted a retrospective review on the use of ibrutinib in 22 children with cGVHD at Cincinnati Children's Hospital Medical Center. All patients received a dose of 250mg/m2 orally, once daily. Responses were measured at 6months after drug initiation using the 2014 NIH consensus panel response criteria. Twenty-two patients of median age 13.5years received ibrutinib. cGVHD grades were severe (n=15), moderate (n=6), and mild (n=1). Eight patients stopped ibrutinib prior to 3months due to adverse events or death and could not be evaluated for 6-month response. Of the 14 evaluable patients, 12 achieved a partial response at 6months and two patients had progressive disease. Seven evaluable patients with lung involvement had stable lung function at 6months. One patient had EBV reactivation, and one patient developed pneumococcal sepsis despite appropriate prophylaxis while on ibrutinib therapy. No fungal infections occurred while on ibrutinib. Adverse events leading to discontinuation included recurrent fevers without a source, extensive bruising, oral bleeding, gastrointestinal distress, lower GI bleeding, dizziness, elevated transaminases, and pneumococcal sepsis. Ibrutinib administration of 250mg/m2 oral daily shows promising responses in pediatric cGVHD. Pediatric-focused pharmacokinetic-directed studies are needed to establish optimal dosing and define efficacy in children.