Effect Of Concurrent Cyp3a4 Interacting Medications On Ibrutinib Outcomes In Patients With Cll.

e19514 Background: Concurrent use of strong CYP3A4 inhibitors increases ibrutinib exposure 20-fold. Hence, use of strong CYP3A4 inhibitors/inducers is not recommended, and moderate inhibitors warrant ibrutinib dose reduction. Concurrent use of ibrutinib and CYP3A4 inducers/inhibitors is inevitable in clinical practice, and may result in adverse events. In this multicenter analysis, we investigated whether concurrent use of CYP3A4 interacting drugs impacts outcomes of ibrutinib therapy. Methods: We performed a retrospective analysis of 141 patients who received ibrutinib therapy for CLL at 4 academic centers. Survival time on ibrutinib was estimated in Cox proportional hazards model. Chi-squared test was used to evaluate discontinuation of ibrutinib due to side effects. Results: 141 patients were treated with ibrutinib, 26 (18%) were concurrently prescribed a moderate or strong inducer or inhibitor of CYP3A4. 24 (17%) were on CYP3A4 inhibitors, most often fluconazole (n = 10) and ciprofloxacin (n = 11), and 2 patients used a CYP3A4 inducer (fosphenytoin, etravirine). 11 (8%) were on CYP3A4 inducers or inhibitors for ≥31 days, of which 4 had ibrutinib dose reduced, and 0 stopped ibrutinib due to adverse events. Although not statistically significant, there is a trend towards improved survival for patients who had ibrutinib dose reduced and were on concurrent CYP3A4 interacting medications versus patients whose ibrutinib was not dose reduced (HR 0.27, p = 0.21, CI 0.04-2.07). There was a strong trend towards improved survival (HR 0.29, p = 0.06, CI 0.08-0.97), and time on ibrutinib therapy (HR 0.33, p = 0.08, CI 0.10-1.13) for patients who did not require therapy with moderate or strong CYP3A4 interacting medications. Patients who took ibrutinib concurrently with CYP3A4 interacting medications did not have an increase on the rate of discontinuation of ibrutinib due to adverse events (p = 0.47). Conclusions: In this real world multicenter dataset, concurrent use of CYP3A4 interacting medications resulted in a trend towards shortened survival and time on ibrutinib. Dose reduction of ibrutinib for CYP3A4 interactions may correct for the change in overall survival seen. Additional data is needed to make a conclusive statement.