Dr. Phillips on the FDA Approval of Pirtobrutinib in MCL

Tycel Phillips, MD, associate clinical professor, Division of Lymphoma, Department of Hematology and Hematopoietic Stem Cell Transplantation, City of Hope, discusses the significance of the FDA approval of pirtobrutinib (Jaypirca) in mantle cell lymphoma (MCL).

On January 27, 2023, the FDA approved pirtobrutinib in patients with MCL previously treated with a BTK inhibitor. The regulatory decision was based on findings from the phase 1/2 BRUIN trial (NCT03740529), which investigated the agent as a monotherapy at once-daily doses of 25 mg, 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, and 300 mg.

In BRUIN, pirtobrutinib elicited an overall response rate (ORR) of 51% in BTK-pretreated patients and 82% in BTK-naïve patients. Additionally, in patients with prior stem cell transplant, the ORR was 64%, and in those with prior CAR T-cell therapy, the ORR was 50%. Responses were also durable, with 60% of patients who responded experiencing ongoing response at a median follow-up of 8.2 months.

The BTK-naïve population achieved an ORR similar to response rates seen with the covalent BTK inhibitors ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa), with a favorable toxicity profile, Phillips says. Common adverse effects of any grade across all doses and cohorts included fatigue, diarrhea, neutropenia, and contusion. No dose-limiting toxicities were reported, and the maximum tolerated dose was not reached. Additionally, the agent elicited strong response rates in the BTK-exposed population, which historically has had few effective and accessible options, Phillips notes.

Prior to the approval of pirtobrutinib, the only approved option for BTK-refractory patients with MCL was brexucabtagene autoleucel (Tecartus), a CAR T-cell product, Phillips explains. As CAR T-cell therapies are often difficult to access, given the requirement for them to be administered in CAR T–approved centers, the approval of this new agent expands treatment access in the post-BTK inhibitor setting, as it can be given at all oncology treatment centers, Phillips concludes.