Dr. Torka on BTK Inhibitors Available for Patients With R/R MCL

Pallawi Torka, MD, assistant attending physician, Memorial Sloan Kettering Cancer Center, discusses the BTK inhibitors available for treatment of patients with relapsed/refractory mantle cell lymphoma (MCL).

Four BTK inhibitors have been approved by the FDA for the treatment of patients with relapsed/refractory MCL, Torka begins. Ibrutinib (Imbruvica), which was a first-generation BTK inhibitor, was the first BTK inhibitor approved in this space, and the second-generation BTK inhibitors acalabrutinib (Calquence) and zanubrutinib (Brukinsa) later followed. In January 2023, the FDA approved pirtobrutinib (Jaypirca) for patients with relapsed or refractory MCL who have received at least 2 prior lines of therapy, including a BTK inhibitor, based on findings from the phase 1/2 BRUIN trial (NCT03740529).

Since pirtobrutinib is currently approved for use after a prior BTK inhibitor, ibrutinib, acalabrutinib, and zanubrutinib are the first options for patients with relapsed/refractory MCL. Torka notes that in her clinical practice, ibrutinib has drifted away from being a preferred agent, and she are typically opts for either acalabrutinib or zanubrutinib.

In the past, Torka’s preference leaned toward acalabrutinib, unless a patient was on a proton pump inhibitor, which would serve as a contraindication, in which case zanubrutinib would be preferred, Torka says. However, acalabrutinib now has a formulation which is proton pump inhibitor agnostic, making it a viable option for those patients. Selecting between acalabrutinib and zanubrutinib may come down to physician preference and other patient factors, but Torka adds that both are good choices. The preference for acalabrutinib or zanubrutinib over ibrutinib stems from a better safety profile and slightly better efficacy, Torka continues.

Since pirtobrutinib is indicated for patients after disease progression on another BTK inhibitor, it is not a consideration in the same setting as the other 3 BTK inhibitors. For patients who do experience disease progression on a BTK inhibitor, pirtobrutinib represents a viable option, Torka concludes.