Grzegorz S. Nowakowski, MD, assistant professor of medicine at Mayo Clinic, discusses the desire to use biological heterogeneity as a factor for treatment in newly diagnosed patients with mantle cell lymphoma (MCL).

One factor that he is not yet taking into consideration but would like to is biological heterogeneity of the disease, Nowakowski explains. There are some patients with relatively indolent disease progressing over the years, while other patients have rapidly progressive MCL. The vast majority of patients come right in the middle, he adds. Having a biologic prognostic factor would help predict the clinical course of those patients, as it would assist physicians in selecting the most appropriate therapy for them.

A certain attempt is being made with the NanoString platform in conjunction with the MCL55 assay, which uses gene expression profiling from paraffin-embedded tissue.  

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Dr. Nowakowski on Biological Heterogeneity  in Newly Diagnosed Patients With MCL

Grzegorz S. Nowakowski, MD, assistant professor of medicine at Mayo Clinic, discusses what potential immunotherapy agents have in the treatment landscape of mantle cell lymphoma (MCL).

The activity of single-agent PD-1 inhibitors in MCL has not been as significant as has been seen in Hodgkin lymphoma, Nowakowski explains. Therefore, it would be interesting to explore combinations of immunotherapy agents with other systemic therapies. For example, lenalidomide (Revlimid) is an immunomodulatory agent that stimulates the immune system, so a combination of PD-1 blockade plus lenalidomide could be an interesting approach in MCL. These studies are currently ongoing.

PD-1 inhibitors with cytotoxic therapy would also be an intriguing option, because chemotherapy traditionally tends to introduce additional mutations within tumor cells. Additional mutations can create new epitopes or antigens, which can then be recognized by the immune system, he says.

Dr. Nowakowski on the Potential Role of Immunotherapy in MCL

Grzegorz S. Nowakowski, MD, an assistant professor of Medicine at Mayo Clinic, discusses the status of emerging agents moving through the pipeline of mantle cell lymphoma (MCL).

The agent that is closest to frontline therapy is the combination of lenalidomide (Revlimid) and rituximab (Rituxan), Nowakowski explains, which is also known as R-squared. This combination has been compared in a randomized study against chemoimmunotherapy with results that are now maturing. Another study demonstrated the benefit of maintenance therapy with rituximab in the post-induction setting for elderly patients, as well as following high-dose chemotherapy and autologous transplantation in young and fit patients.

Targeted therapies are being tested in the relapsed/refractory setting and are slowly moving to the upfront setting, he explains. Ibrutinib (Imbruvica) is one that has significant single-agent activity in MCL. The addition of ibrutinib is being studied with bendamustine and rituximab (BR) against BR alone in an ongoing phase III study.

Finally, venetoclax (Venclexta) was recently found to have significant single-agent activity in MCL. What is interesting, he says, is to see combinations of venetoclax and ibrutinib together in an effort to lose the chemotherapy backbone.

Grzegorz S. Nowakowski, MD, an assistant professor of Medicine at Mayo Clinic, discusses the status of emerging agents moving through the pipeline of mantle cell lymphoma.

Dr. Nowakowski on Next Steps With Emerging Agents in MCL

Grzegorz Nowakowski, MD, assistant professor of medicine, Mayo Clinic, discusses the evolving treatment paradigm of mantle cell lymphoma (MCL).

MCL is an area where a lot of new agents are being developed, Nowakowski explains. Moreover, what is interesting is that there is a paradigm shift from chemotherapy-based combinations to targeted therapy-based regimens in the relapsed setting. These include ibrutinib (Imbruvica) plus rituximab (Rituxan) and lenalidomide (Revlimid) and rituximab. Venetoclax (Venclexta) is another agent being explored in these regimens.

Over time, some of these more novel regimens are likely to replace chemotherapy in the relapsed setting, he adds..

Grzegorz S. Nowakowski, MD

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Dr. Nowakowski on Biological Heterogeneity in Newly Diagnosed Patients With MCL

Dr. Nowakowski on the Potential Role of Immunotherapy in MCL

Dr. Nowakowski on Next Steps With Emerging Agents in MCL

Dr. Nowakowski on Evolving Treatment Paradigm of MCL