Options When Mantle Cell Lymphoma Relapses

Because relapse is so common, doctors sometimes opt to supplement the initial treatment and continue treating patients even after they've achieved remission, hoping to prevent or at least postpone a relapse.  "One big question in mantle cell lymphoma is whether or not a remission upfront should be consolidated with a stem cell transplant," says Dr. Elise Chong, a hematologist/oncologist at Penn Medicine.

Doctors don't really know yet whether this "extra" treatment upfront will help prevent relapse. "The answer to that is currently being studied in clinical trials," explains Dr. Chong. "Researchers are investigating whether or not patients who are in remission are fine and can be followed after completing chemotherapy, or whether they're best off consolidating that remission, meaning proceeding to an autologous stem cell transplant in that first remission."

After a Relapse

When a patient does relapse after achieving a remission, what to do next depends on several factors, including:

• The length of time since their initial treatment
• The extent of the disease
• The treatments the patient has already received and how effective they were
• The patient’s age and overall health

There’s no consensus among doctors about which therapy is best, and there are many clinical trials underway to further study existing options, and to find new and effective treatments as well. In the meantime, there are many different options available to treat relapsed (returned after remission) or refractory (no longer responding to treatment) mantle cell lymphoma. These include:

• Acalabrutinib (Calquence)
• Bendamustine (Treanda)
• Bortezomib (Velcade)
• Brexucabtagene autoteucel (Tecartus)
• Lenalidomide (Revlimid)
• Zanubrutinib (Brukinsa)

"The major drugs include BTK inhibitors … as well as Revlimid, with or without Rituxan," says Dr. Chong, who explains that if a patient hasn't already received these drugs, they're non-chemotherapy agents that "have a lot of activity in mantle cell lymphoma and are quite exciting."

BTK inhibitors work by blocking the protein called Bruton's tyrosine kinase, or BTK that mantle cell lymphoma cells need to grow. Calquence and Brukinsa are also BTK inhibitors. These three BTK inhibitors come in pill forms that a patient takes once or twice a day.

Revlimid is a drug that spurs the immune system to kill more cancer cells, stop new cells from growing, and cut off the growth of blood vessels so cancer cells don't have the blood supply they need to survive. It also comes in pill form.

These drugs may be combined with Rituxan, a monoclonal antibody that works with the immune system to destroy cancer cells.

Another promising option, according to Dr. Chong, is CAR T-cell therapy. "This is one of the newest approved therapies for mantle cell lymphoma, and it's exciting. It was previously only approved for aggressive B-cell lymphomas." CAR T cells are immune system T cells that have been genetically engineered to recognize and kill mantle cell lymphoma cells.

A stem cell transplant, if not done earlier as part of initial treatment, can also be very effective. The transplant may be autologous (using a patient's own harvested stem cells) or allogenic (retrieved from a compatible donor). Because of the risk of rejection from donor cells, allogenic transplants are considered riskier but also potentially curable.

There are many clinical trials underway to determine which existing drugs provide the best outcome and whether specific combinations of drugs work better. There are also many clinical trials investigating a variety of new drugs for their effectiveness in treating mantle cell lymphoma, either initially or after a relapse. Patients with mantle cell lymphoma should ask their doctor about whether it would be beneficial for them to volunteer for one of these trials.

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