We identified all patients with chronic lymphocytic leukemia at Mayo Clinic treated with ibrutinib outside the context of a clinical trial; timing and reasons for discontinuation were ascertained, as were symptoms, exam and radiographic findings, and laboratory changes following discontinuation. Of 202 patients who received ibrutinib, 52 discontinued therapy (estimated 1- and 2-year risk of discontinuation 18% and 28%, respectively). The most common reasons for discontinuation were toxicity (56%) and progression of disease (32%, including Richter's transformation in 15%). Rapid progression of disease within 4 weeks after discontinuation was observed in 9/36 (25%) patients with adequate records for review, mostly in those stopping ibrutinib for disease progression (n = 8) rather than toxicity (n = 1). This was evident by sudden worsening of disease-related symptoms (n = 9), exam/radiographic changes (n = 7), and laboratory changes (n = 8). An estimated one in every three patients discontinued ibrutinib by 2 years, with 25% developing rapid disease progression afterwards.
Keywords: Chronic lymphocytic leukemia (CLL); discontinuation; ibrutinib; progression.