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All-oral combination regimens represent a transformative advancement in chronic lymphocytic leukemia (CLL) treatment, offering patients fixed-duration therapy options without requiring intravenous infusions. These combinations, particularly BTK inhibitors paired with venetoclax, are revolutionizing the treatment landscape by providing convenient, effective therapy that significantly improves patient quality of life. The elimination of intravenous requirements reduces clinic visit frequency and allows greater treatment flexibility, making therapy more accessible and manageable for patients with CLL.
The most significant advancement with oral combination therapies is their efficacy in high-risk CLL populations, particularly patients with TP53 mutations or 17p deletions. While the CAPTIVATE study showed limitations for ibrutinib-venetoclax combinations in high-risk patients, newer trials like AMPLIFY with acalabrutinib-venetoclax and SEQUOIA with zanubrutinib-venetoclax demonstrate improved outcomes in these challenging cases. These regimens appear to address the critical unmet need for effective treatments in high-risk CLL, offering hope for previously difficult-to-treat patient populations.
Selecting from available oral combination regimens requires consideration of patient-specific factors, including genetic risk profiles, comorbidities, and individual tolerance concerns. For patients with TP53/17p abnormalities, zanubrutinib-venetoclax may be preferred based on SEQUOIA data, while other factors like hypertension management might influence Bruton tyrosine kinase inhibitor selection. The availability of multiple effective oral combinations allows for truly personalized CLL treatment approaches, matching regimen characteristics to individual patient needs and disease characteristics for optimal outcomes.