One of the most important things to recognize is that a subset of patients with more indolent disease can be expectantly monitored for 2 or 3 years without introducing treatment-associated toxicities and without sacrificing overall survival or quality of life. This applies to approximately 15% to 20% of all patients with MCL and is perhaps especially salient when considering older or unfit individuals, who may not do as well with treatment.

In planning for individualization of treatment/treatment intensity, beyond chronological age, we are interested in understanding a patient's comorbidities, particularly those that may impact cardiovascular, pulmonary, renal, or liver function, all of which can impact therapeutic strategies. Review of the medication list is important because some treatments can interact with preexisting medications or may increase the risk of atrial fibrillation, bleeding, or other complications. An assessment of the patient’s overall fitness and performance status is also very important. When looking to stratify patients for therapy by frailty/fitness, it is helpful to be mindful of typical components in a formal geriatric assessment, such as nutritional status, mobility, cognitive status, and the ability to perform activities of daily living. One can learn a great deal by asking the patient to describe a typical day. It is also important to engage the patient in an attempt to truly understand their preferences and whether they are interested in an intensive treatment approach, assuming that they are a candidate. And then, the cost of therapy may be a consideration. So, you really put all of these factors together when working with patients to determine which approach makes the most sense.

For older patients with typically aggressive MCL who are very fit, intensive cytarabine-based treatment followed by autologous stem cell transplantation is not out of the question. However, the most widely utilized initial approach in older, fit patients is the combination of rituximab and bendamustine. Other regimens for older, fit patients can include the combination of rituximab, bendamustine, and cytarabine and R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by rituximab maintenance. In my practice, I do not typically use an anthracycline-based regimen in this older/unfit population because it is associated with more toxicity, including risk for cardiomyopathy. Lenalidomide in combination with rituximab may be a useful option in those who cannot tolerate more intensive therapy; however, it is an indefinite therapy, and lenalidomide, although not chemotherapy, has a known side-effect profile to contend with, including—but not limited to—fatigue, myalgias and arthralgias, cytopenias, and risk for venous thromboembolism. Bruton tyrosine kinase inhibitors are US Food and Drug Administration approved for MCL in the relapsed/refractory setting, and frontline combinations involving Bruton tyrosine kinase inhibition, monoclonal antibodies, and/or small molecules are actively being explored in clinical trials for MCL. Finally, some of my patients who are particularly frail and have multiple comorbidities can achieve some level of disease control with single-agent monoclonal antibody therapy.