There does appear to be a biologically distinct clinical entity that meets the definition of indolent MCL: the so-called leukemic non-nodal variant that tends to be SOX11 negative, is more likely to have a leukemic presentation with splenomegaly, and is less likely to have significant lymphadenopathy. These patients are less likely to have symptoms, and the MCL may initially present very similarly to chronic lymphocytic leukemia, which underscores the importance of appropriate diagnostic testing. Alternatively, a patient with classical aggressive MCL may initially appear to be low risk based on the fact that they have a low tumor burden at diagnosis. This is usually due to early detection, based on the presentation (eg, perhaps a palpable cervical lymph node that led to diagnosis). 

In a scenario involving a patient with indolent non-nodal MCL, with no symptoms and a low tumor burden, who is started on watch and wait, it is important to remember that even indolent non-nodal MCL can acquire a TP53 mutation and become a clinical problem. Thus, it is important to maintain vigilance during surveillance. In the other scenario involving a patient with a more classic MCL presentation, but with low tumor burden and no symptoms, I think that it is perfectly reasonable to start them on a watch-and-wait strategy. This will allow the clinician to get a handle on the pace of the disease for that particular patient. In each case, the initial strategy is the same, and, in each case, you would monitor for clinical indications to initiate treatment. These would include the development of symptoms or signs of more rapid progression and progression toward a high tumor burden. Another indication for starting treatment is the development of cytopenias, as splenomegaly and marrow infiltration can become pronounced in certain patients with MCL, leading to the development of anemia or thrombocytopenia. 

When the patient becomes symptomatic, whether the presentation was leukemic non-nodal MCL or classical MCL, you proceed with treatment. If the patient is under 65 years of age, I would likely lean toward a more aggressive approach initially. However, there are other factors to consider, including the patient’s underlying health status and comorbidities. I may adjust my recommended approach based on what I have learned from the patient during discussions regarding treatment options. The patient’s perspectives should be considered. What are their goals and preferences? In my view, intensive treatment would involve a frontline strategy that contains high-dose chemotherapy, such as the hyper-CVAD regimen (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), or any regimen that includes autologous stem cell transplantation. Such treatment can become too toxic as patients get older. Nonintensive options include regular-intensity chemotherapy such as bendamustine and rituximab, R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), or VR-CAP (bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone) regimens. We do not know for certain that aggressive treatment strategies will improve survival in younger patients with indolent MCL, although we are fairly confident that they will produce longer first remissions. Thus, I will have this discussion with patients and let them weigh in on their personal preferences.