Dr Cohen on the Efficacy of Pirtobrutinib in High-Risk Patients With MCL

Jonathon B. Cohen, MD, MS, associate professor, the Department of Hematology and Medical Oncology, co-director, Lymphoma Program, university chair, Data and Safety Monitoring Committee, Winship Cancer Institute, Emory University School of Medicine, discusses safety and efficacy outcomes with pirtobrutinib (Jaypirca) in previously treated patients with relapsed/refractory mantle cell lymphoma (MCL), as observed in the phase 1/2 BRUIN study (NCT03740529).

At the 2023 ASH Annual Meeting, investigators presented updated findings on patients with relapsed/refractory MCL from the BRUIN trial, including additional follow-up from a larger cohort of newly accrued patients, Cohen begins.

Extended follow-up data demonstrated that pirtobrutinib continues to exhibit promising efficacy in heavily pretreated patients with relapsed/refractory MCL following prior BTK inhibitor therapy. The median duration of response with pirtobrutinib in this patient population was 21.6 months (n = 152; 95% CI, 9.2-27.2). Pirtobrutinib displayed clinically meaningful efficacy across various MCL subgroups, including patients who had received prior BTK inhibitor therapy, displayed high-risk molecular features, such as a higher Ki-67 index and TP53 mutations, or had BTK inhibitor–naive disease.

Additionally, pirtobrutinib produced an overall response rate of 49.3% (95% CI, 41.1%-57.6%), a median progression-free survival of 5.6 months (95% CI, 5.3-9.2), and a median overall survival (OS) of 23.5 months (95% CI, 17.1-not evaluable [NE]).

This is notable given the historically short median OS associated with in this patient population, Cohen explains. Responders to the therapy exhibited robust and enduring responses, Cohen notes.

The agent was well tolerated, with low rates of discontinuation due to drug-related toxicity, Cohencontinues. There were no unexpected safety signals or significant changes from previous reports, hesays. Although some patients experienced fatigue and cytopenias, known toxicities associated with BTK inhibitors, such as bleeding and cardiac complications, were generally low, Cohen emphasizes. For example, the incidence of atrial fibrillation was minimal, and included a low risk of grade 3 or greater atrial fibrillation or flutter, he states.

These data further establish pirtobrutinib as a new standard of care for this patient population. The randomized global phase 3 BRUIN MCL-321 trial (NCT04662255) comparing pirtobrutinib with theinvestigator’s choice of BTK inhibitor is ongoing in relapsed BTK inhibitor–naive MCL.