Outcomes following exposure to drug interactions with ibrutinib in patients with chronic lymphocytic leukaemia.

Abstract

Ibrutinib is metabolized by cytochrome P450 3A (CYP3A) and poses challenges with drug interactions. We conducted a population-based cohort study of Ontario residents aged ≥66 years who initiated ibrutinib for chronic lymphocytic leukaemia (CLL) to evaluate the frequency of potential drug interactions involving moderate/strong CYP3A inhibitors and inducers and their association with overall survival (OS). Secondary analyses employed a nested case-control design examining hospitalizations for haemorrhage or infection as potential markers of ibrutinib toxicity. Among 642 ibrutinib recipients (median age 74 years, 34.4% female), 70 (10.9%) received a concomitant CYP3A inducer while 404 (62.9%) received a concomitant CYP3A inhibitor. In the primary analysis, we found no association between death (n = 162) and concurrent use of either moderate/strong CYP3A inducers or inhibitors. In secondary analyses, 86 patients (13.4%) were admitted to hospital for bleeding and 287 patients (44.7%) for infection. Receipt of moderate/strong CYP3A inhibitors was associated with an increased odds of hospitalization for infection (odds ratio 2.88, 95% confidence intervals [CI] 1.29-6.43) but not haemorrhage. Among older patients receiving ibrutinib for CLL, concomitant use of CYP3A-modulating drugs is common. We found no association between use of interacting drugs and OS, but CYP3A inhibitors were strongly associated with hospitalization for infection, underscoring the importance of pharmacovigilance.