Dr. Mukherjee on the Role of Disease Biology in the Treatment of MCL

Akash Mukherjee, MD, hematologist, oncologist, University of Arkansas for Medical Sciences, (UAMS), assistant professor, Division of Hematology/Oncology, the Winthrop Cancer Institute, the UAMS College of Medicine, discusses the importance of understanding disease biology when attempting to individualize treatment approaches in mantle cell lymphoma (MCL).

Understanding the classification of nodal morphology is critical in assessing a patient’s disease biology, Mukherjee begins. Patients with MCL can exhibit classical or blastoid/pleomorphic MCL morphologies, Mukherjee says. Previous clinical trials have shown that blastoid and pleomorphic morphological variants are characterized by a more aggressive disease course compared with a classical morphology, Mukherjee says.

Additionally, the presence of TP53 mutations and Ki-67 levels greater than 30% are associated with high-risk status and inferior patient prognosis, Mukherjee continues. These contributing factors are assessed in the MCL International Prognostic Index (MIPI). The index uses data from patients treated in previous clinical trials to characterize patients as high, low, or intermediate risk, and accordingly predict survival outcomes. The 4 independent risk factors included in a patient’s MIPI score are age, ECOG performance status, lactate dehydrogenase (LDH), and leukocyte count, he explains.

In addition to disease biology, it is also important to identify patients who exhibit the leukemic variant of MCL (LV-MCL), Mukherjee states. Patients in this subgroup often display slow or absent clinical progression and are asymptomatic and can present similarly to patients with chronic lymphocytic leukemia, he notes. For example, patients with the indolent variant may display mild-moderate lymphocytosis, mild lymphadenopathy, slight pancytopenia, or mild hepatosplenomegaly without demonstrating transfusion dependence or other high-risk factors, Mukherjee details. Correctly identifying this genetically distinct variant could better inform treatment decisions, as patients with LV-MCL may not need immediate treatment, Mukherjee emphasizes. These patients should instead be monitored and repeatedly examined every 3 months until treatment becomes necessary, Mukherjee concludes.