Dr DeAngelo on Non-Chemotherapy Treatment Options in CLL

“Most patients nowadays are being treated initially with BTK inhibitors and then progressing on to a combination of venetoclax and a monoclonal [anti-]CD20 antibody.”

Daniel DeAngelo, MD, PhD, professor, medicine, Harvard Medical School, chief, Division of Leukemia, institute physician, Dana-Farber Cancer Institute, discusses how the hematology field’sshift away from chemotherapy has affected treatment strategies for chronic lymphocytic leukemia (CLL).

The transition away from chemotherapy as the mainstay treatment for CLL has transformed therapeutic strategies for this disease, DeAngelo begins. CLL management often involves monitoring asymptomatic patients with stage 0 disease until symptoms arise, at which point intervention becomes necessary, according to DeAngelo. Previously, chemotherapy was the default treatment choice; however, it now plays a limited role due to the availability of more targeted therapies, he emphasizes. For instance, the introduction of BTK inhibitors into the treatment paradigm has redefined treatment standards, he says. Ibrutinib (Imbruvica) was the first BTK inhibitor to receive regulatory approval, but its association with significant cardiotoxicities, particularly atrial fibrillation, has led to caution in its use, he notes. Although all BTK inhibitors are associated with a degree of cardiovascular risk, newer agents like acalabrutinib (Calquence) and zanubrutinib (Brukinsa) have demonstrated reduced toxicity profiles, DeAngelo states. Consequently, ibrutinib has seen a decline in usage in favor of these newer alternatives, he adds.

For patients seeking a time-limited treatment option or those who develop resistance to standard BTK inhibitors, the combination of venetoclax (Venclexta) and obinutuzumab (Gazyva) has become a viable choice, he continues. Additionally, the FDA approval of a new noncovalent inhibitor, pirtobrutinib (Jaypirca), offers an option for patients exhibiting resistance to existing BTK inhibitors, DeAngelo shares.

In current practice, chemotherapy is largely reserved for a select group of younger patients with specific genetic markers, such as IGH-mutated favorable-risk disease or those with wild-type TP53status, he expands. However, for the majority of patients with CLL, initial treatment now typically involves BTK inhibitors, with progression to combinations like venetoclax and a monoclonal CD20 antibody, further underscoring the shift toward precision-targeted therapies over traditional chemotherapy, DeAngelo concludes.