Expectant monitoring is a very important management strategy in up to 30% of patients with MCL who have indolent or slow-growing disease and do not require the immediate initiation of therapy. Although we do not have the perfect tools for predicting the duration of expectant monitoring in patients with MCL, we know that many patients with indolent MCL can enjoy an extended treatment-free period, with the median duration being 2 to 3 years, depending on the series. This can be an important period because patients are able to avoid treatment-related toxicities and it gives research an opportunity to progress, which allows for the development of newer novel therapies that may eventually benefit the patient. 

In addition, there are some subsets of patients with MCL in whom the early initiation of therapy may lead to the selection of more resistant strains of the disease. For example, a subclone that harbors the TP53 mutation may emerge if a patient is treated initially with chemoimmunotherapy, and then that disease may become very challenging to treat. 

A main question is: How do you decide which patients to monitor? We have learned more about the biologic characteristics of MCL that are associated with a favorable prognosis or indolent, slow-growing disease. For example, a subset of MCL called non-nodal leukemic MCL has been added to the World Health Organization classification system for lymphoid malignancies. This subset of MCL looks very similar to chronic lymphocytic leukemia in that patients may present with a leukemic phase of disease, with an elevated lymphocyte count, and frequently with splenomegaly. Typically, these individuals do not have enlarged lymph nodes, and the disease is limited to the peripheral blood, the bone marrow, and/or the spleen. The biologic characteristics that are associated with more indolent disease include a low proliferation rate or Ki-67, immunoglobulin heavy chain that has undergone somatic hypermutation, and the absence of expression of the transcription factor SOX11. I have a few patients in my practice with non-nodal leukemic MCL who have been observed alone for more than 10 years. Other patients with MCL who may be good candidates for expectant monitoring include those who are asymptomatic with microscopic gastrointestinal tract involvement and those with a low tumor burden.

One of the interesting things that has been observed as we look more closely at these non-nodal leukemic MCL cases is that such patients can have evidence of a TP53 mutation or 17p deletion in the absence of cytopenias or other indications for immediate therapy. If these patients do not have bulky disease, there is no organ compression, their blood counts are normal, and they are feeling well, then even they may be candidates for expectant monitoring. Those with blastic or pleomorphic MCL histologic subtypes are not good candidates for monitoring because they typically have rapidly proliferative disease. But, in the absence of that, based on our data, we see that there should not be any biologic characteristics that absolutely exclude a patient from initial monitoring.