Why Mantle Cell Lymphoma Can Be Hard to Treat

Medically Reviewed by Melinda Ratini, MS, DO on February 24, 2023
3 min read

Mantle cell lymphoma tends to grow quickly. When doctors find this type of cancer, it’s usually widespread throughout your body already. This can make treatment more difficult. But doctors have many tools in their toolboxes, including medicines and other therapies, to treat all stages of this type of lymphoma.

Staging can tell you how much the lymphoma has spread and where. Doctors group lymphoma into four different stages:

Stage I. You either have lymphoma in one lymph node, a single group of lymph nodes, an organ of your lymphatic system, or in another single site other than your lymph nodes.

Stage II. The lymphoma is either in two or more groups of lymph nodes or in a non-lymph node site as well as one or more groups of lymph nodes. In either case, the cancer is limited to one side of the body.

Stage III. You have lymphoma on both sides of your body. This could mean it’s in lymph nodes on both sides of your diaphragm. Or it could be in nodes above your diaphragm and in your spleen.

Stage IV. The lymphoma is in many lymph nodes and at least one non-lymph node site, such as your liver, bones, or lungs.

Your doctor may tell you that you have limited (early) or advanced lymphoma. Limited stage lymphoma usually means that you are at stage I or II. Advanced stage means your disease is in stage III or IV.

The stage of your mantle cell lymphoma helps doctors decide which form of care is best for you. Your doctors also consider other factors like:

  • The grade of your cancer (the look of the cells or the number of cells in your lymphoma)
  • Your symptoms
  • The location of the cancer
  • Your age
  • Any other health conditions that you have

If the lymphoma is slow-growing and you don’t have any major symptoms, your doctor might not suggest treatment right away. They may use a method called “active monitoring” or “watch and wait.” This means that your care team will observe your health at regular checkups. You won’t begin actual treatment unless the condition starts to affect your health.

This approach allows you to avoid the side effects of medication for as long as possible. Starting therapy before your doctor recommends it won’t help you get healthier. If you do begin to develop symptoms, your doctor will put you on treatment right away.


Cancer cells tend to grow much faster than normal, healthy cells. Chemotherapy uses chemicals to kill fast-growing cells in the body. It’s a common treatment for mantle cell lymphoma.

If you’re relatively healthy and young, doctors will want to treat the disease aggressively with intense chemotherapy often with the immunotherapy drug, rituximab. Rituximab is a targeted drug that helps your body’s own immune system kill off cancer cells. They may use one of the following combinations:

  • Hyper-CVAD: Cyclophosphamide, vincristine, doxorubicin, and dexamethasone, high-dose methotrexate, and cytarabine.
  • “Dose-intensified” R-CHOP: Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.
  • R-DHAP: Rituximab, dexamethasone, cytarabine, cisplatin.

People who are older or have underlying health issues may not tolerate such powerful chemo drugs. In this case, doctors may start with something milder, such as bendamustine (Belrapzo, Bendeka, Treanda) with rituximab.

If these treatments are effective, doctors might want to follow it with a stem cell transplant. A stem cell transplant replaces your damaged blood cells with healthy new ones.

After this, you will likely take rituximab for 3 years.

Sometimes mantle cell lymphoma doesn’t respond to treatment, or the disease comes back later. In these cases, doctors will give you additional medication. This might include:

  • Chemotherapy with drugs like bendamustine (Belrapzo, Bendeka, Treanda), bortezomib (Velcade), cladribine (Litak, Mavenclad), fludarabine (Fludara), or lenalidomide (Revlimid). Your doctor may use these alongside other chemotherapy drugs or with rituximab.
  • Targeted drugs, like acalabrutinib (Calquence), ibrutinib (Imbruvica), pirtobrutinib (Jaypirca) or zanubrutinib (Brukinsa). These types of drugs shut down one step in the cancer-spreading process so that the cancer cannot continue to grow and progress.
  • CAR T-cell therapy with brexucabtagene autoleucel (Tecartus). This treatment soups up your body’s own immune cells so that they can kill off the cancer.

Some other targeted drugs, like venetoclax (Venclexta) and idelalisib (Zydelig), also seem to be effective in early studies.