Dr Pearse on the Utility of Pirtobrutinib in Relapsed/Refractory MCL

William B. Pearse, MD, assistant professor, medicine, University of California, San Diego (UCSD), UCSD School of Medicine, discusses the current role of the BTK inhibitor pirtobrutinib (Jaypirca) in the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL). Notably, in January 2023, pirtobrutinib was FDA approved for the treatment of patients with this disease following at least 2 lines of systemic therapy, including a BTK inhibitor.

The optimal sequencing of pirtobrutinib and other BTK inhibitors remains an area of active investigation, Pearse begins. The ongoing MCL 135 BRUIN MCL 321 study (NCT04662255) is a phase 3, open-label, randomized trial designed to explore this question, he states, saying that the study will compare pirtobrutinib against an investigator’s choice of BTK inhibitor in patients with previously treated, BTK inhibitor–naive MCL. By evaluating pirtobrutinib's safety and efficacy relative to established BTK inhibitors, such as acalabrutinib (Calquence) or zanubrutinib (Brukinsa), researchers hope to shed light on the potential for pirtobrutinib as a frontline treatment option in MCL, Pearse elucidates.

One key aspect of the MCL 135 study is its exploration of moving pirtobrutinib earlier in the treatment sequence, he expands. This shift seeks to determine whether initiating therapy with pirtobrutinib yields improved efficacy and safety outcomes compared with standard BTK inhibitors in the second-line relapsed/refractory setting, he explains. Additionally, the study provides an opportunity for head-to-head comparisons between acalabrutinib and zanubrutinib, 2 commonly used BTK inhibitors, in the second-line setting, Pearse says. This comparative analysis promises to enrich the MCL field’s understanding of these agents' respective efficacy and safety profiles, as well as their suitability for different patient populations, he notes.

Although existing data on BTK inhibitors in the second-line relapsed/refractory setting are limited, ongoing trials, such as the MCL 135 study, hold promise for addressing critical gaps in knowledge, Pearse continues. By prospectively evaluating different BTK inhibitors and their sequencing strategies, researchers aim to refine treatment approaches for patients with MCL, according to Pearse. Ultimately, insights gleaned from these trials have the potential to inform clinical decision-making and optimize patient outcomes in the management of MCL, he concludes.