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.
Department of Pharmacy, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA. waldrom@ccf.org.
Madeline
0000-0001-8113-5254
M
Waldron
Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
Allison
A
Winter
Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
Brian T
BT
Hill
D000225:Adenine / Q000031:analogs & derivatives; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D004347:Drug Interactions; D018565:Food-Drug Interactions; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy*; D010880:Piperidines; D011687:Purines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D011720:Pyrazoles / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D052999:Quinazolinones / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010880:Piperidines; D011687:Purines; D011720:Pyrazoles; D011743:Pyrimidines; D052999:Quinazolinones; D013449:Sulfonamides; C551803:ibrutinib; D000225:Adenine; C579720:venetoclax; C552946:idelalisib