Dr. Torka on the Role of Pirtobrutinib in R/R MCL

Pallawi Torka, MD, assistant attending physician, Memorial Sloan Kettering Cancer Center, discusses the clinical implications of the FDA approval of pirtobrutinib (Jaypirca) in patients with relapsed or refractory mantle cell lymphoma (MCL).

On January 27, 2023, the FDA approved pirtobrutinib in adult patients with relapsed/refractory MCL who have received at least 2 prior lines of therapy, including a BTK inhibitor. The approval was backed by findings from the phase 1/2 BRUIN trial (NCT03740529), in which treatment with the agent at 200 mg daily led to an overall response rate of 50%, including a 13% complete response rate.

Pirtobrutinib represents an additional BTK inhibitor option for patients with MCL, especially older patients in whom CAR T-cell therapy may not be an option, Torka says. Prior to the FDA approval of pirtobrutinib, once patients with MCL relapsed on first-line therapy, they typically received a BTK inhibitor followed by CAR T-cell therapy after they relapsed on the BTK inhibitor, Torka explains. Brexucabtagene autoleucel (Tecartus; brexu-cel) was approved by the FDA in 2020 for adult patients with relapsed or refractory MCL, based on findings from the phase 2 ZUMA-2 trial (NCT02601313).

Before switching from a BTK inhibitor to CAR T-cell therapy, most patients need bridging therapy, especially those who are receiving treatment at a community cancer center and need to wait to be referred to a site that administers CAR T-cell therapy, Torka notes. Bridging therapy for patients with MCL can include venetoclax (Venclexta) or additional chemotherapy agents such as bendamustine, Torka says. Now, pirtobrutinib can also be considered as a bridging therapy, as it is not toxic to stem cells and does not cause adverse effects to T cells, Torka emphasizes.

Another advantage of pirtobrutinib is its toxicity profile, Torka explains. In the BRUIN trial, 36% of patients received the agent for at least 6 months, and 10% received it for at least 1 year. Additionally, 4.7% of patients required adverse effect (AE)–related dose reductions, and 32% of patients needed AE-related pirtobrutinib interruptions. AEs of grade 3 or higher included fatigue, edema, musculoskeletal pain, arthritis or arthralgia, abdominal pain, dyspnea, pneumonia, upper respiratory tract infections, peripheral neuropathy, and hemorrhage.

In older adults with MCL who often have few therapeutic options, pirtobrutinib provides an extra option that can help patients live longer with minimal AEs, Torka concludes.