Dr. Heyman on the Evolution of BTK Inhibitors in Relapsed/Refractory MCL

Benjamin Heyman, MD, assistant clinical professor, Medicine, hematologist, Moores Cancer Center, University of California, San Diego Health, discusses the evolution of BTK inhibitors in relapsed/refractory mantle cell lymphoma (MCL).

The introduction of single-agent BTK inhibitors transformed the treatment of patients with relapsed/refractory MCL, Heyman says. Long-term data with single-agent ibrutinib (Imbruvica) demonstrated an overall response rate of approximately 70% and complete response rate of approximately 30%. However, responses appear to be dependent on timing of treatment. For example, patients with 1 prior line of therapy have superior responses compared with those who received 2 or more prior lines of therapy, Heyman explains.

The second-generation covalent BTK inhibitors acalabrutinib (Calquence) and zanubrutinib (Brukinsa) are also FDA approved for use in patients with relapsed/refractory MCL, Heyman says. Without cross-trial comparisons, it is difficult to determine whether these agents demonstrate improved efficacy vs ibrutinib; however, acalabrutinib and zanubrutinib are associated with less hematologic adverse effects and reduced risk of cardiovascular toxicities compared with ibrutinib, Heyman says.

Additionally, noncovalent BTK inhibitors, such as pirtobrutinib (LOXO-305), as well as combination regimens with ibrutinib and venetoclax (Venclexta) or CD20-directed monoclonal antibodies appear to be promising strategies to improve response rates, outcomes, and duration of response, Heyman concludes.