Dr Visco on Unmet Needs for Patients With Mantle Cell Lymphoma

“When we look out there at the MCL field, the number one high-risk factor and matter pf consideration is TP53 mutation [status]. We need to study more on that. We need to better define these mutations.”

Carlo Visco, MD, an associate professor of hematology in the Department of Medicine, coordinator of the Lymphoma Team in the Hematology and Bone Marrow Transplant Unit in the Section of Biomedical Innovation in the Department of Engineering for Innovative Medicine at the University of Verona, discussed unmet treatment needs for patients with mantle cell lymphoma (MCL) that may inform future research in this patient population.

TP53 mutation status stands as the primary high-risk factor and the most critical matter of consideration in the MCL field, Visco began. Patients presenting with disease that harbors this mutation do not achieve prolonged remissions when treated with standard immunochemotherapy, he said. Furthermore, when treated upfront with combination therapies, including covalent BTK inhibitors, these patients have demonstrated inferior overall survival (OS) outcomes compared with those without TP53-mutated disease, he noted. Even modern therapeutic approaches, such as pirtobrutinib (Jaypirca) and CAR T-cell therapies, have been associated with dismal OS rates for this patient population, he added.

Given these poor outcomes, there is a recognized necessity to further study TP53 mutations in MCL, according to Visco. It is essential to better define these mutations, recognizing that significant differences may exist between individual mutational profiles, he continued. Hematologists must also consider how these mutations rely on or combine with other known risk factors, including clinical and histopathological factors, he reported. These high-risk patients should be clustered into rigorous, well-defined groups, and treatment methods for these patients should be unique. To address the need for differential MCL management strategies based on risk, the prospective, phase 2 FIL_V-RBAC trial (NCT03567876) was conducted as the first of its kind to stratify MCL patients to receive different treatments according to their risk profiles.