Dr Goy on the Influence of High-Risk Features on Treatment Decision-Making in MCL

Andre Goy, MD, physician in chief, Hackensack Meridian Health Oncology Care Transformation Services, chairman, chief physician officer, chief, Lymphoma Division, John Theurer Cancer Center, Hackensack University Medical Center, discusses the prevalence of high-risk clinical features in patients with mantle cell lymphoma (MCL) and their influence on treatment approaches.

The standard approach to treatment in MCL has shifted over time to have a larger focus on integrating novel therapies into the paradigm and identifying which patient populations benefit most from these agents in the first-line setting and beyond, Goy begins. This includes a better understanding of what constitutes as a high-risk population. High-risk disease is defined by factors such as MCL International Prognostic Index score, Ki-67 proliferation, disease progression after 24 months, and minimal residual disease (MRD) negativity, Goy details, noting that the latter 2 criteria can help inform treatment selection at baseline or during the disease course.

MRD negativity is increasingly recognized as a significant end point in MCL, although it is not yet a part of the standard routine, Goy continues. However, the identification of high-risk patients extends beyond conventional criteria. Next-generation sequencing (NGS) has emerged as a valuable tool for identifying high-risk genetic features in MCL, he says. Approximately 25% to 30% of patients exhibit high-risk features, including TP53 mutations, 17p deletions, or complex karyotypes, Goy states. As a frequently observed feature in MCL, complex karyotypes are generally unstable even without a blastoid variant, Goy explains.

Understanding the genetic complexity of MCL through NGS provides clinicians with a comprehensive view of the disease's signature, Goy says. Unlike standard presentations, some MCL cases with seemingly typical features reveal complex, high-risk genetic features through NGS, he adds. Identifying this high-risk subset early in treatment is crucial to patient outcomes, Goy emphasizes.

Long-term data from Europe further underscore the importance of identifying high-risk genetic abnormalities early in the disease course for this high-risk population, Goy notes. For example, patients with TP53 mutations exhibit a lower median overall survival vs those without such features and have a poorer prognosis with treatments like high-dose therapy or transplant, Goy reports. This knowledge prompts a paradigm shift in the approach to managing high-risk MCL, emphasizing the importance of tailored therapies based on genetic insights, he says. As these genetic variations become more easily identifiable through NGS, the goal is to integrate this information into routine clinical practice, allowing for more precise risk stratification and personalized treatment strategies, Goy concludes.