CLL Patients on Concomitant Ibrutinib Therapy Should Be Carefully Evaluated

As 2 out of 3 patients with chronic lymphocytic leukemia (CLL) are undergoing concomitant therapy with ibrutinib, hematologists are urged to conduct formal medication reviews in these patients.¹

Researchers led by Heidi Finnes, PharmD, of the Mayo Clinic in Rochester, MN, looked at 96 patients who started ibrutinib off-protocol from November 2013 to July 2015 in order to determine drug-drug interactions. They measured for time to toxicity and ibrutinib discontinuation with Kaplan Meier and cumulative incidence methods.

Sixty patients were found to be taking concurrent medications, thereby increasing their risk of ibrutinib toxicity, while 4 patients were on drugs potentially reducing ibrutinib efficacy.

Upon initiation, 16 patients were on concomitant 3A4 inhibitors, including 9 on moderate and 7 on strong. In 4 patients, the 3A4 inhibitor was switched to another agent or discontinued in order to allow standard 420 mg daily dosing. In addition, 4 patients were on strong 3A4 inducers upon ibrutinib initiation, which was discontinued prior to ibrutinib start in 3 patients.

Upon commencing ibrutinib, 9 patients were found to be on concomitant anticoagulant medication. Warfarin was switched to enoxaparin in 2 patients, to aspirin in 1 patient, and warfarin was discontinued in 1 patient. Ten patients were found to have clinically significant bleeding on ibrutinib, including 4 who required hospitalization.

After median follow-up of 7.6 months, 73 patients remained on ibrutinib therapy, and there was found to be no difference in rates of discontinuation of ibrutinib between patients who were on 3A4 inhibitors/inducers compared to those who were not.

Reference

1. Finnes HD, Chaffee KG, Call TG, et al. The importance of pharmacovigilance during ibrutinib therapy for chronic lymphocytic leukemia (CLL) in routine clinical practice [abstract]. Blood. 2015;126(3):717.