One of the confounding features that we encounter in the treatment of patients with MCL is the heterogeneity of presentation and progression of the disease. When approaching a patient with asymptomatic MCL, it is important to consider the patient’s age, comorbidities, and prognostic factors, including the Mantle Cell Lymphoma International Prognostic Index score, positron emission tomography/computed tomography standardized update values, serum lactate dehydrogenase and β² microglobulin levels, NOTCH1 and NOTCH2 mutations, and the Ki-67 proliferative index. The stratification of patients into risk categories is particularly important in the era of multi-agent chemotherapy. The 5-year survival rate of individuals with MCL in the lowest risk category may exceed 60%, while those in the intermediate- and high-risk categories may have median survival rates of approximately 50 months and 30 months, respectively.

The patient’s ability to recover from multi-agent chemotherapy is another major consideration. Hematopoietic cellularity in the bone marrow declines with age, potentially inhibiting an older individual’s ability to recover from combination chemotherapy and leading to future problems with persistent anemia and thrombocytopenia. Unfortunately, when we are treating patients with fairly aggressive disease, we typically tend to throw the book at them. But, even after being treated with extensive multi-agent chemotherapy involving a variety of different agents, such as the hyper-CVAD and CHOP regimens, the disease will likely recur, particularly among those in the intermediate- and high-risk categories. In this situation, we are left with patients with impaired bone marrow function and treatment-related comorbidities that can influence subsequent treatment decisions.

In my experience, approximately 20% of newly diagnosed patients with MCL can be safely observed and monitored approximately every 3 months for signs of disease progression and complications that may mandate therapy. In low-risk patients, deferred therapy may be associated with improved outcomes, including the preservation of bone marrow function and increases in survival. Individuals with MCL are likely to have major concerns about mortality, loss of control, and complications of therapy. I think that a tremendous degree of reassurance is provided when patients feel that you are on top of things, are knowledgeable about their prognostic status, and will be diligent about surveying for progression and disease-related complications.