Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Chronic Lymphocytic Leukemia: Ibrutinib, Idelalisib, and Venetoclax
Management of chronic lymphocytic leukemia has changed markedly over the last several years with the emergence of several novel oral agents targeting B-cell receptor and Bcl-2 signaling pathways. For patients requiring treatment, ibrutinib, idelalisib, and venetoclax offer unique clinical benefits with a different set of therapeutic considerations compared with traditional parenteral therapy. Despite the conveniences afforded by oral therapy, these agents also carry unique logistical obstacles. Drug interactions with agents that are metabolized via the cytochrome P450 3A4 pathway are possible with all three agents. Unique treatment-related adverse events including bleeding and atrial fibrillation with ibrutinib, hepatotoxicity with idelalisib, and tumor lysis syndrome with venetoclax can be severe and dose limiting. Furthermore, dose adjustments for organ dysfunction may also be warranted. Here, we review the available literature on the pharmacokinetic and pharmacodynamic properties of these novel agents to guide the reader in the appropriate use of ibrutinib, idelalisib, and venetoclax.
KeywordsChronic Lymphocytic Leukemia Grapefruit Juice CYP3A4 Inhibitor Chronic Lymphocytic Leukemia Cell Absolute Lymphocyte Count
Compliance with ethical standards
Conflict of interest
Dr. Brian Hill serves on the advisory board for Pharmacyclics and Gilead. He has received research funding from Abbvie and Gilead. Dr. Allison Winter and Dr. Madeline Waldron have no conflicts of interest to report that are directly relevant to the content of this article.
No funding was received in the preparation of this manuscript.
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