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

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.