Taking on Mantle Cell Lymphoma: MSK Leads Research into New Treatments

By Jim Stallard,

MSK medical oncologist Anita Kumar
Summary

Although there is no standard therapy for mantle cell lymphoma, treatment has improved significantly over the last decade. New drugs are currently being tested in a variety of clinical trials.

Mantle cell lymphoma (MCL) is a rare but fast-growing form of non-Hodgkin lymphoma. It is diagnosed in about 4,500 people in the United States each year. The disease arises from white blood cells in the lymph nodes called B lymphocytes — specifically those found in the outer ring of the lymph nodes, known as the mantle zone. Most cases are detected at a late stage, after the disease has spread, typically to the bone marrow, digestive tract, spleen, or liver. Even after successful treatment, MCL often returns and can be difficult to cure.

MCL has long proved challenging for doctors because there is no established, standard therapy. Instead, there is a range of treatment options, and doctors have had to make judgment calls without much clinical data to guide their decisions. But Memorial Sloan Kettering clinicians and researchers are playing a leading role in improving outcomes with a variety of clinical trials testing new drugs.

“Someone who searches for mantle cell lymphoma online is likely to see poor survival estimates, but those numbers do not at all reflect the progress that has occurred in recent years,” says MSK medical oncologist Anita Kumar, who specializes in the treatment of lymphomas, and specifically MCL. “I think there are a lot of reasons for optimism in the field.”

Our doctors and patients explain why MSK is leading the way in diagnosing and treating lymphoma.

Despite the rareness of MCL, Dr. Kumar and her colleagues in the Lymphoma Service have extensive expertise in treating the disease. They also are incorporating insights about the molecular and genomic diversity of MCL into the effort to develop more-effective therapies.

“Understanding the biology better has helped us tailor individualized treatment approaches,” she says. “We have a clearer picture of which types of MCL are slow growing and can potentially be observed in the short term, and which are aggressive and need treatment right away.”

Support for People Newly Diagnosed with MCL

Treatment of newly diagnosed MCL depends partly on the person’s age and overall health. For people who are young and fit, the most common approach includes four chemotherapy drugs combined with the monoclonal antibody rituximab (Rituxan®) — a regimen called R-CHOP. These patients often receive an additional chemotherapy drug called cytarabine. The chemotherapy is followed by an autologous stem cell transplant, which uses the patient’s own immune cells. Older, less fit patients may receive less-intensive chemotherapy, such as a drug called bendamustine (Treanda®) along with rituximab.

“The overall prognosis has improved significantly for newly diagnosed patients because of improvements in upfront treatment,” Dr. Kumar says.

Researchers want to build on the success of these treatments and further reduce the chance that the cancer will return. MSK has completed a phase II clinical trial to see whether incorporating a drug called lenalidomide into chemotherapy treatment will help prevent MCL from returning. Lenalidomide affects the immune system in a way that helps to stop cancer cells from growing.

In the trial, lenalidomide is given along with R-CHOP chemotherapy, followed by rituximab and cytarabine. Then lenalidomide and rituximab are given as maintenance treatment after chemotherapy.

“We think lenalidomide maintenance could be effective in getting rid of leftover tumor cells that remain after chemotherapy treatment, resulting in longer periods before the cancer returns,” Dr. Kumar says. “Early results from the study suggest this leads to remission in almost all cases.”

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Fighting Mantle Cell Lymphoma When It Comes Back

MCL that returns, or recurs, has been hard to treat because it is more resistant to chemotherapy. But in recent years, several new drugs have emerged that target specific proteins driving the cancer’s growth. Two categories of drugs that are highly effective for the treatment of recurrent MCL are kinase inhibitors and BCL-2 inhibitors.

Ibrutinib (Imbruvica®), a kinase inhibitor, was approved by the US Food and Drug Administration in 2013 for treating MCL that recurs and is resistant to other treatments.

“Ibrutinib has shown effectiveness against MCL. We hope that by combining it with other drugs, we can overcome treatment resistance and see more patients achieve complete remissions that last even longer than with ibrutinib alone,” explains Dr. Kumar.

MSK is conducting a phase III trial testing whether ibrutinib could be even more effective if combined with a BCL-2 inhibitor called venetoclax (Venclexta®). Venetoclax is already approved by the FDA to treat people with a different type of B cell lymphoma called small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). It is a recommended treatment for recurrent MCL in the National Comprehensive Cancer Network guidelines.

Another strategy involves combining ibrutinib with a second kinase inhibitor called buparlisib that targets a different protein. A phase I/IB clinical trial investigating this combination has shown promising results, suggesting the drugs work together to cause cancer cell death.

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Exploring Novel Treatments

MSK has one of the world’s most active programs investigating immunotherapy for the treatment of lymphoma, including MCL. A phase I/IB trial is testing a type of immunotherapy drug called a bispecific antibody. These drugs are designed to target a protein called CD20 on B cells and CD3 on immune T cells. This triggers an immune response by directing the T cells to kill the cancerous B cells.

Another trial is investigating chimeric antigen receptor (CAR) T cell therapy. This technique involves removing some of a patient’s immune cells and genetically modifying them to find and kill cancer cells. In 2017, the first CAR T cell therapy was approved by the FDA for aggressive diffuse large B cell lymphoma — another non-Hodgkin lymphoma. The hope is that the treatment will also work against MCL. 

“This field is moving so fast with the number of treatment options becoming available that we expect to see continued progress toward higher response rates, more durable remissions, and hopefully a cure in many future cases,” Dr. Kumar says.

Learn more about clinical trials at MSK for people with mantle cell lymphoma.

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