Approval of First BTK Inhibitor to Treat Pediatric Graft-Versus-Host Disease 

Ibrutinib, a small molecule inhibitor of B-cell proliferation, was approved for pediatric patients with chronic graft-versus-host disease. 

The U.S. Food and Drug Administration (FDA) has approved ibrutinib (Imbruvica) for pediatric patients 1 year of age or older who have chronic graft-versus-host disease (cGvHD) that did not respond to prior lines of systemic therapy.  

Ibrutinib is an irreversible small molecule inhibitor of Bruton’s tyrosine kinase (BTK), a protein that is involved in B-cell receptor signaling and is required for malignant B-cell proliferation. Inhibition of BTK results in decreased proliferation of malignant B cells. Ibrutinib is the first BTK inhibitor approved for pediatric patients with cGvHD. It was approved for adult patients with cGvHD in 2017.  

The pediatric approval is based on results from the open-label, multicenter, single-arm iMAGINE phase I/II clinical trial. 

The iMAGINE trial enrolled 47 patients between the ages of 1 and 19 years who had moderate or severe cGVHD and required additional therapy after at least one prior line of systemic therapy. The median age of enrolled patients was 13 years. Sixty percent of patients experienced an objective response by week 25 post-treatment. The median duration of response was 5.3 months, and the median time from first response to death or new systemic therapies for cGVHD was 14.8 months. 

Common adverse reactions included anemia, musculoskeletal pain, fever, diarrhea, pneumonia, abdominal pain, stomatitis, thrombocytopenia, and headache. 

GvHD is a potentially serious complication of allogeneic stem cell transplantation, a procedure frequently utilized to treat pediatric patients with blood cancers. This disease develops when the transplanted immune cells attack the patients’ healthy cells. It is estimated that 5 to 30 percent of pediatric patients undergoing stem cell transplantation will develop GvHD. 

The FDA rendered its decision on June 24, 2022.