Dr. Kahl on a Potential Limitation of Frontline BTK Inhibitor Combos in MCL

Brad S. Kahl, MD, professor of medicine, Department of Medicine, Oncology Division, Medical Oncology, Washington University School of Medicine in St. Louis, discusses a potential limitation of frontline combination strategies with BTK inhibitors in mantle cell lymphoma (MCL).

Studies are evaluating the first-line utility of BTK inhibitors in combination with chemoimmunotherapy in patients with MCL, Kahl says. However, if a patient progresses on a first-line BTK inhibitor, they then become refractory to BTK inhibitors, which limits available options in subsequent lines of treatment, Kahl explains. Moreover, when looking at mechanisms of resistance, if a patient becomes resistant to ibrutinib (Imbruvica) or acalabrutinib (Calquence), it is likely they will be resistant to the other agent as well, Kahl says.

However, investigational noncovalent BTK inhibitors could have activity in patients who progress on covalent BTK inhibitors. Although these agents are not FDA approved, they may offer potential options for ibrutinib- or acalabrutinib-resistant patients, Kahl says. Additionally, although BTK inhibitor options are limited, CAR T-cell therapies are also available, as are other FDA-approved agents. Ultimately, whether BTK inhibitors have utility as frontline therapy remains unknown until additional data are published, Kahl concludes.