Dr Deng on BTK Inhibitors vs Venetoclax-Based Treatment Regimens in CLL/SLL

Changchun Deng, MD, PhD, associate professor, hematology/oncology, University Hospitals Seidman Cancer Center; member, Immune Oncology Program, Case Comprehensive Cancer Center, discusses considerations for covalent BTK inhibitors vs venetoclax (Venclexta)–based treatment regimens for patients with chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL).

Several key considerations guide CLL/SLL management, including the presence of high-risk genetic factors, notably TP53 mutations and 17p deletions, which significantly influence oncologists’ choices of therapy, Deng says. Although other disease factors, such as 11q deletions and unmutated IGHV status, are considered high-risk features, they may not weigh as heavily in the decision-making process compared with TP53 mutations and 17p deletions due to their implications on treatment response, he says.

For patients with both a 17p deletion and a TP53 mutation who require treatment, a covalent BTK inhibitor is typically favored, especially if patients are open to receiving therapy indefinitely, Deng continues. Currently, there are 3 approved covalent BTK inhibitors: zanubrutinib (Brukinsa), acalabrutinib (Calquence), and ibrutinib (Imbruvica). The choice among these inhibitors is nuanced and may depend on factors such as the patient's risk of developing atrial fibrillation, a notable concern associated with BTK inhibitors, making individualized treatment selection paramount, he reports.

The decision to use a covalent BTK inhibitor vs a BCL-2 inhibitor such as venetoclax is intricately linked to patient preferences and long-term disease management strategies, Deng expands. Covalent BTK inhibitors offer a continuous treatment approach suitable for patients willing to commit to ongoing therapy, according to Deng. In contrast, venetoclax-based regimens, particularly when combined with anti-CD20 monoclonal antibodies, may present a time-limited treatment option with the potential for yielding deep remissions, including minimal residual disease negativity, he adds.

Ultimately, the choice between a covalent BTK inhibitor and a venetoclax-based regimen involves a comprehensive assessment of genetic risk factors; patient preferences regarding treatment duration and regimen tolerability; and considerations of the evolving CLL/SLL treatment armamentarium, Deng concludes.