Ibrutinib-Induced Vasculitis in a Patient with Metastatic ColonCancer Treated in Combination with Cetuximab

Combination therapy with ibrutinib and cetuximab is being studied in a phase 1b/2 trial in patients with advanced gastrointestinaland genitourinary malignancies. Rash is a common cutaneous adverse effect for both medications. Ibrutinib is a Bruton’s tyrosinekinase (BTK) inhibitor approved for the treatment of several hematologic malignancies. The rash can be asymptomatic,nonpalpable, mild skin eruption, or palpable purpuric rash. A rarer panniculitis form has also been reported. Cetuximab, anepidermal growth factor (EGFR) inhibitor, approved for treatment in head and neck and advanced gastrointestinal malignanciesis also known to cause acneiform rash in majority of patients. The rash is due to inhibition of EGFR in the basal keratinocytesand hair follicles. In the case of ibrutinib, the off-target effects on EGFR, c-kit, and platelet-derived growth factor receptor(PDGFR) are thought to be responsible for the cutaneous eruption of various forms of rash. The combination therapy with theBTK inhibitor and a direct EGFR inhibitor may potentiate the rash inducing effects of the drugs. Here, we describe a case ofvasculitis in a patient with metastatic colon cancer who received both ibrutinib and cetuximab on a phase Ib/II clinical trial.