Pharmacovigilance during ibrutinib therapy for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in routine clinical practice

Abstract

Due to Cytochrome P450 3A (CYP3A) metabolism, clinical trials of ibrutinib-treated chronic lymphocytic leukemia (CLL) patients prohibited concurrent medications metabolized by CYP3A. We evaluated concomitant medication use in 118 ibrutinib-treated CLL patients outside the context of clinical trials. Seventy-five (64%) patients were on medications that could increase ibrutinib toxicity and 4 (3%) were on drugs that could decrease ibrutinib efficacy. Nineteen (16%) patients were on concomitant CYP3A inhibitors (11 moderate, 8 strong), and 4 (3%) were on CYP3A inducers (two patients were on both CYP3A inhibitors and inducers). Although the ibrutinib starting dose was changed in 18 patients on CYP3A interacting medications, no difference in 18-month progression-free survival or rate of ibrutinib discontinuation was observed in patients who were not. In routine clinical practice, 2 of 3 CLL patients commencing ibrutinib are on a concomitant medication with potential to influence ibrutinib metabolism. Formal medication review by a pharmacist should be considered in all patients initiating ibrutinib.

Keywords:

• Pharmacotherapeutics
• chemotherapeutic approaches
• prognostication

Acknowledgements and Research Support

This work was supported by funding from the National Cancer Institute [grants K12 CA090628 to Sameer Parikh, MD, K23CA160345 to Wei Ding, MD, CA95241 to Neil Kay, MD and K12 CA090628 to Saad Kenderian MD] and in part by the Predolin Foundation.

Tait D. Shanafelt, MD is a clinical scholar of the Leukemia and Lymphoma Society.

Previous Presentation of this Research

The results of this study were presented at the 57th Annual American Society of Hematology Meeting in Orlando, FL in December 2015.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at http://dx.doi.org/10.1080/10428194.2016.1251592.