Agammaglobulinaemia Tyrosine Kinase; Antineoplastic Agents; Disease-Free Survival; Dose-Response Relationship, Drug; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Mutation; Patient Compliance; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrazoles; Pyrimidines; Tumor Suppressor Protein p53
Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that was maintained at 24 hours. It is unknown if intermittent interruption of ibrutinib therapy contributes to altered clinical outcomes. We therefore evaluated the effect of ibrutinib dose adherence on patient outcomes in the phase 3 RESONATE trial. The overall mean dose intensity (DI) was 95% with median treatment duration of ∼9 months. Pharmacokinetic assessment of ibrutinib exposure at 420-mg dose suggested similar exposure regardless of patient weight or age. As assessed by independent review committee, patients with higher DI experienced longer median progression-free survival (PFS) compared with those with lower DI regardless of del17p and/or
Barr, Paul M; Brown, Jennifer R; Hillmen, Peter; O'Brien, Susan; Barrientos, Jacqueline C; Reddy, Nishitha M; Coutre, Steven; Mulligan, Stephen P; Jaeger, Ulrich; Furman, Richard R; Cymbalista, Florence; Montillo, Marco; Dearden, Claire; Robak, Tadeusz; Moreno, Carol; Pagel, John M; Burger, Jan A; Suzuki, Samuel; Sukbuntherng, Juthamas; Cole, George; James, Danelle F; and Byrd, John C, "Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL/SLL." (2017). Articles, Abstracts, and Reports. 1570.