Dr. Moustafa on Clinical Implications of the BRUIN Trial of Pirtobrutinib in MCL

Muhamad Alhaj Moustafa, MD, MS, hematologist/medical oncologist, Mayo Clinic, assistant professor, Mayo Clinic School of Medicine, discusses how the approval of pirtobrutinib (Jayprica) has improved the treatment of patients with mantle cell lymphoma (MCL), and the role that this agent has in the current treatment landscape.

Patients with relapsed/refractory MCL are historically characterized as having poor prognosis, and are not likely to experience responses with chemoimmunotherapy regimens, Moustafa begins. Although the introduction of first-generation BTK inhibitors marked the beginning of a transformation in the management of patients with MCL, treatment options were limited for those whose disease relapsed on prior BTK inhibitor therapy, he states. The recent approval of CAR T-cell therapies in MCL serves as a viable option in the third-line setting, Moustafa notes, but these patient still lack effective alternatives once they experience disease progression on CAR T-cell therapy.

In January 2023, pirtobrutinib gained FDA approval for patients with relapsed/refractory MCL who had been previously exposed to at least 2 prior lines of systemic therapy, including a BTK inhibitor. This regulatory decision was supported by efficacy data from the phase 1/2 BRUIN trial (NCT03740529).

Updated results from the trial have demonstrated that pirtobrutinib produced an overall response rate (ORR) of 56.7% in a subset of 90 patients with MCL, Moustafa reports. This consisted of a 18.9% complete response rate and a 37.8% partial response rate, he adds. Moreover, the median duration of response was 17.6 months at a median follow-up of 12.7 months. Additional analysis of survival outcomes revealed that pirtobrutinib produced a median progression-free survival of 7.4 months and a median overall survival of 23.5 months.

Overall, pirtobrutinib is a vital addition to the treatment armamentarium for patients with MCL in the third line and beyond, Moustafa concludes.