Preventing life-threatening human allergic reactions with ibrutinib

Approximately 15 million people (8% of children) in the US have food allergy and are at risk for life-threatening anaphylactic reactions. There is an unmet need for treatments capable of preventing such reactions. In late 2013, the FDA granted accelerated approval to a first-in-class kinase inhibitor, ibrutinib, for two types of relapsed/refractory lymphoid malignancies based on remarkable efficacy and limited toxicity. The target of this drug, a protein inside of cells called Bruton’s tyrosine kinase (Btk), is also essential for triggering of cells involved in allergic reactions. We therefore hypothesize that ibrutinib will effectively prevent allergic reactions with tolerable toxicity. We will identify a cohort with lymphoid malignancies planning to start ibrutinib therapy with known or suspected environmental allergies. Conventional allergy skin testing will be performed before and during exposure to ibrutinib. Blood samples will be obtained simultaneously to study allergic cells (“basophils”) in the laboratory. We anticipate that individuals taking ibrutinib will demonstrate marked if not complete elimination of allergic reactivity, as assessed by skin testing and basophil activation testing. If successful, this pilot study will provide sound rationale for future studies evaluating ibrutinib and other Btk inhibitors for the prevention of allergic reactions including anaphylactic reactions to foods.