Resistance Mutations in Chronic Lymphocytic Leukemia Relapsing After First-Line Treatment With Fixed-Duration Ibrutinib Plus Venetoclax

Results from the phase 2 CAPTIVATE study demonstrated that first-line treatment with fixed-duration ibrutinib plus venetoclax provides deep, durable responses and sustained progression-free survival with a favorable safety profile in young, fit patients with chronic lymphocytic leukemia. In the current analysis, no resistance-associated mutations in BTK, PLCG2, or BCL2 were identified in samples from patients experiencing progressive disease after completion of fixed-duration ibrutinib plus venetoclax. These results suggest that fixed-duration combination treatment with ibrutinib plus venetoclax may mitigate the development of resistance mechanisms associated with continuous single-agent targeted therapies and allow for effective retreatment with ibrutinib or ibrutinib plus venetoclax, thereby extending clinical benefit with these agents.