Dr Cohen on Available Treatments For MCL

Jonathon B. Cohen, MD, MS, associate professor, Department of Hematology and Medical Oncology, codirector, Lymphoma Program, university chair, Data and Safety Monitoring Committee, Winship Cancer Institute, Emory University School of Medicine, discusses the current treatment paradigm for patients with relapsed/refractory mantle cell lymphoma (MCL), highlighting the background of the phase 1/2 BRUIN study (NCT03740529) of treatment with pirtobrutinib (Jaypirca) in previously treated patients.

During the 2023 ASH Annual Meeting, updated results from the BRUIN trial were presented, featuring extended follow-up data on a larger cohort of newly enrolled patients. The findings highlighted pirtobrutinib's efficacy in heavily pretreated patients with relapsed/refractory MCL after prior BTK inhibitor therapy (n = 152). Notably, the median duration of response with pirtobrutinib in this group reached 21.6 months (95% CI, 9.2-27.2), and the agent had meaningful efficacy across various MCL subgroups, including patients with high-risk molecular features or BTK inhibitor–naive disease. Furthermore, pirtobrutinib led to 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) in patients who had received a prior covalent BTK inhibitor.

MCL is a relatively rare type of non-Hodgkin lymphoma known for its aggressive nature, Cohen begins. Despite treatment advancements for patients with this disease, OS remains poor for patients progressing after treatment with covalent BTK inhibitors, he states. Research efforts in the current era aim to enhance outcomes for patients with relapsed MCL, and investigators are exploring new oral therapies, CAR T-cell treatments, and immunotherapies, Cohen explains.

The phase 1/2 BRUIN study assessed the noncovalent BTK inhibitor pirtobrutinib in various B-cell malignancies, with chronic lymphocytic leukemia and MCL being the most prevalent, he expands. Initially, the study aimed to determine the optimal dosage of pirtobrutinib for phase 2 evaluation, focusing on the agent’s efficacy, particularly in patients previously treated with covalent BTK inhibitors, Cohen elucidates.

Patients with relapsed or refractory MCL were eligible for inclusion, with most having prior exposure to BTK inhibitors, although a small subset were treatment naive, he continues. Patients needed a reasonable ECOG performance status and stable blood counts, according to Cohen. However, the BRUIN investigators aimed to make the study accessible to as many patients as possible. Compared with trials investigating more intensive therapies, inclusion criteria for BRUIN were less restrictive, allowing broader patient participation, Cohen concludes.