MCL is a heterogenous disease. One of the first steps at initial diagnosis is to examine the tumor biology, including the Ki-67 proliferation index and TP53 and 17p deletion mutations. We look at patient characteristics, such as chronological and physiologic age and comorbidities, as well as the extent of disease.

Patients with a very low Ki-67, who often have blood and bone marrow involvement but without a lot of systemic disease, tend to behave in a very indolent fashion. They can be managed with watch-and-wait strategies, and this is especially applicable in older patients and/or in those with other comorbidities. Some of these individuals can defer treatment for several months, or even years. When an older patient with asymptomatic MCL becomes symptomatic and requires therapy, a number of treatment options are available. Additionally, we move forward with treatment in a patient with MCL who presents with any of the following symptoms: anemia or pancytopenia, painful splenomegaly, or gastrointestinal bleeding from MCL involvement.

Patients with the blastoid variant of MCL who are younger and in otherwise good physical condition are usually treated aggressively, typically with cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine (hyper-CVAD) plus rituximab followed by ASCT. Lumbar puncture and cerebrospinal fluid analysis for both cytology and flow cytometry are recommended, as central nervous system prophylaxis is often indicated in patients with the blastoid variant of MCL. ASCT or even allogeneic stem cell transplantation may be considered following induction therapy.

In younger patients without the blastoid variant of MCL, a number of different options are available for induction. One option is a cytarabine-containing regimen, such as the NORDIC regimen (ie, dose-intensified induction chemoimmunotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone [maxi-CHOP] alternating with rituximab plus high-dose cytarabine). Hyper-CVAD plus rituximab is used in some institutions, but we have stopped using this regimen because we felt that it was too toxic for this particular patient population. Typically, we would offer or consider ASCT at the first complete response in this patient population. There are no randomized studies to prove that it is better, but retrospective analyses indicate that it does appear that patients who can undergo ASCT have better outcomes.

The optimal treatment approach is not as “black-and-white” in MCL as it is in some other lymphomas. You want to discuss all of the information with the patient and their family, help them to understand the options, and include them in the treatment decisions.