Based on the current data, the decision to administer MCL chemotherapies in sequence or in combination is influenced by disease characteristics (ie, type of MCL) and patient characteristics (ie, patient age, patient comorbidities). The use of individual sequential therapies would, perhaps, be more appropriate in patients with asymptomatic indolent MCL or in older patients with multiple comorbidities. I would be more inclined to administer combination therapy in cases of aggressive MCL and in younger patients without comorbidities. With respect to combinations, some of our best results have been achieved with intensive induction therapies that include rituximab followed by autologous stem cell transplant (ASCT) and then post-transplant rituximab maintenance; however, not all patients can tolerate this approach. Some current trials are examining combinations of Bruton tyrosine kinase inhibitors such as ibrutinib and acalabrutinib with antibodies or venetoclax, but it is too early to determine whether these combinations will offer improvements over the currently used regimens. The use of prognostic biomarkers can help to identify suitable candidates for investigational sequences or combination chemotherapies. In particular, it has recently been shown that those with TP53 aberrations have a shorter time to treatment failure and poor overall survival, independent of both Mantle Cell Lymphoma International Prognostic Index score and the Ki-67 proliferation index. These individuals may benefit from clinical trials, since outcomes are poor—even with intensive treatments.

Approaches to patient monitoring during treatment may vary, depending on whether the patient is receiving sequential or combination chemotherapy. In patients receiving aggressive induction therapy followed by ASCT and maintenance therapy, I would recommend aggressive monitoring that includes positron emission tomography (PET) scans and bone marrow biopsies. In patients receiving individual or sequential treatments, we may be less aggressive about performing computed tomography scans and bone marrow biopsies and more focused on symptom relief and side effects. Thus far, the availability of novel agents has not had a major impact on our approach to patient monitoring during treatment. Some clinical trials are looking at minimal residual disease testing based on genomic sequencing of the lymphoma and identifying those sequences in the blood. Individuals who appear to be in complete remission based on PET scans and bone marrow biopsies may have residual disease based on the appearance of specific genomic sequences previously identified.