What to Do if Mantle Cell Lymphoma Comes Back

Medically Reviewed by Brunilda Nazario, MD on December 21, 2020

Your treatment for mantle cell lymphoma may put you into remission, which means you no longer have signs of cancer. But after a while, your cancer may return. If it does, it doesn't mean you're out of options. Your doctor may suggest other medicines that may work for you.

The medical term for cancer that comes back is "relapse." If it happens to you, your doctor will choose a drug or combination of medications based on things like your age, overall health, how long you were in remission, and which treatments you've already tried and how well they worked.

You may get the same treatment you had before if it was helpful. If your cancer comes back more than once, you might need a different treatment each time.

Targeted Drugs

Targeted drugs focus on specific substances in your body that help your cancer grow. Acalabrutinib (Calquence), ibrutinib (Imbruvica), and zanubrutinib (Brukinsa) are ones that doctors suggest for people who are having a relapse of mantle cell lymphoma. The medicines are called BTK inhibitors because they block the protein Bruton's tyrosine kinase (BTK), which mantle cell cancer cells need to grow.

A targeted drug might be right for you if you've tried at least one other treatment. Acalabrutinib, ibrutinib, and zanubrutinib come as pills that you take once or twice a day.

BTK inhibitors can cause side effects. The most common ones are:

  • Low blood cell counts
  • Headache
  • Diarrhea
  • Tiredness
  • Bruises
  • Muscle pain

Other possible problems include:

  • Excess bleeding
  • Infections
  • Abnormal heart rhythms
  • Another cancer, such as skin cancer

Talk to your doctor if you have any side effects. You might be able to get treatment that controls them.

Lenalidomide (Revlimid)

Lenalidomide (Revlimid) is a drug that acts on your immune system -- your body's defense against germs -- to kill cancer cells. It ramps up your immune system to attack the cancer, stops new cancer cells from growing, and blocks the growth of blood vessels that feed the cancer.

You could get this drug if you've tried at least two other treatments and one of them was the chemotherapy drug bortezomib (Velcade).

Lenalidomide comes in a pill. You take it once a day for 21 days, and then you stop using it for a week.

The medicine has a "black box warning" -- the FDA's strongest alert -- because it can raise the chances of birth defects. If you're a woman and you haven't gone into menopause yet, get tested to make sure you're not pregnant before you start taking this drug. Use two forms of birth control the whole time you're on lenalidomide.

Other possible side effects from lenalidomide include:

  • Low blood cell counts
  • Tiredness
  • Diarrhea
  • Nausea
  • Cough
  • Fever
  • Rash
  • Shortness of breath
  • Itching
  • Constipation

This drug can also cause liver problems and allergic reactions, and it might raise your odds of getting another cancer.

Rituximab (Rituxan)

Rituximab is a type of drug called a monoclonal antibody. It works with your immune system to kill cancer cells.

You may get rituximab together with chemotherapy. Doctors call this combination chemo-immunotherapy. Rituximab can also be combined with BTK inhibitors.


Chemotherapy may have been the first treatment you tried for mantle cell lymphoma. If your doctor recommends it again, this time you'll likely get a different drug or combination of medications.

Chemotherapy drugs that treat relapsed mantle cell lymphoma include:

  • Bendamustine (Bendeka)
  • Bortezomib (Velcade)
  • Cyclophosphamide (Cytoxan, Neosar)
  • Doxorubicin (Adriamycin)
  • Vincristine sulfate (Oncovin)

Sometimes you'll get a few chemotherapy drugs together, along with rituximab or a steroid drug. These drug combinations go by names like R-CHOP and VcR-CAP.

Stem Cell Transplant

One way to put your cancer back into remission, or even cure it, is with a stem cell transplant. First, you'll get very high doses of chemotherapy. The chemo drugs kill lots of cancer cells, but they also kill stem cells -- immature blood cells in your bone marrow and blood. A stem cell transplant replaces the stem cells that were destroyed with healthy cells.

For relapsed mantle cell lymphoma, the stem cells usually come from a donor. This is called an allogeneic stem cell transplant. If you are young and in overall good health, your doctor might use your own stem cells, which is called an autologous stem cell transplant.

Show Sources


American Cancer Society: "Why Are Stem Cell Transplants Used as Cancer Treatment?"

European Medicines Agency: "Revlimid."

FDA: "Calquence Prescribing Information," "Imbruvica Prescribing Information," "Revlimid Prescribing Information."

Lymphoma Action: "Mantle Cell Lymphoma."

Lymphoma Research Foundation: "Mantle Cell Lymphoma: Relapsed/Refractory."

Mayo Clinic: "Rituximab (Intravenous Route)."

National Cancer Institute: "Acalabrutinib Receives FDA Approval for Mantle Cell Lymphoma," "NCI Dictionary of Cancer Terms."

National Comprehensive Cancer Network: "NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas."

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