Overview of mantle cell lymphoma (MCL)
Mantle cell lymphoma (MCL) is usually an aggressive (fast growing) B-cell non-Hodgkin lymphoma. However, in a small proportion of patients it can also behave in a more indolent (slow growing) fashion.
MCL is relatively rare and accounts for around 3-5 percent of all lymphomas and approximately 5-10 percent of all NHL cases. The disease is called ‘mantle cell lymphoma’ because the lymphoma cells grow from the ‘mantle zone’ (the outer edge) of the lymph node
Who is affected by mantle cell lymphoma (MCL)?
Men are likely to be diagnosed at the rate of 3 times more than women with Mantle cell lymphoma (MCL) . The average age at diagnosis of MCL is 70 years and over and MCL is very rare in younger adults.
As with all lymphomas, generally the cause is unknown, however a genetic defect has been seen in many patients who have been later diagnosed with MCL.
Around 85% of people with MCL have a characteristic genetic change in the malignant (cancerous) B-cells where two chromosomes, 11 and 14, break apart and then join together with each other. This is called translocation and causes the cells to produce too much of the protein called cyclin D1. In normal quantities, cyclin D1 helps to promote normal cell growth, however an excess results in uncontrolled growth of the mantle zone cells which lead to MCL.
Symptoms of mantle cell lymphoma (MCL)
Mantle cell lymphoma (MCL) can start anywhere in the body and can have many different symptoms. The exact symptoms can be dependent on the type of lymphoma and where it is located in the body. Most symptoms of lymphoma can also be symptoms of many other illnesses. Because the symptoms can be very general, it can be hard to diagnose. Some common symptoms include:
- Painless lumps in the neck, groin or armpit, that are enlarged lymph nodes. These usually grow quickly
- Other sites of the body include the spleen, the bone marrow, blood, tonsils, lungs, liver, brain/spinal cord and gut.
- If MCL grows around the gut, it can result in diarrhoea, blood in stools or iron deficiency.
- Abdominal bloating
- Loss of appetite
- Fatigue (tiredness or lack of energy)
- Itchy body
B symptoms are related to the following symptoms and can include:
- Night sweats (drenching sleepwear or bedding)
- Persistent fevers (especially at night >38C)
- Unexplained weight loss
Diagnosis and staging of mantle cell lymphoma (MCL)
A biopsy is always required for diagnosis of lymphoma. A biopsy is a surgical procedure to remove part of or all of an affected lymph node or other tissue to be viewed under the microscope by a pathologist. The biopsy can be done under local or a general anaesthetic depending on what part of the body is being biopsied. The biopsy can be done one of three ways:
- Fine needle aspirate
- Core needle biopsy
- Excisional node biopsy
An excisional node biopsy is the best investigative option, as it collects the most adequate amount of tissue to be able to do the necessary testing for a diagnosis.
Waiting for test results can be a difficult time. It may help to talk with family, friends or a specialist cancer nurse.
Staging of lymphoma
Once a diagnosis of MCL is made, further tests are required to see where else in the body the lymphoma has affected or is located. This is called staging. The staging of the lymphoma helps the clinician decide the best treatment
There are four stages from stage 1 (lymphoma in one area) through to stage 4 (lymphoma that is widespread).
- Early stage means stage 1 and some stage 2 lymphoma. This can also be referred to as ‘localised’. Stage 1 or 2 means that the lymphoma is found in one area or a few areas close together.
- Advanced stage means the lymphoma is stage 3 and stage 4, and it is widespread. In most cases, the lymphoma has spread to many parts of the body that are far from each other.
What is the ‘grade’ of MCL
Lymphomas are also often grouped as either indolent or aggressive. Indolent lymphomas are usually slow growing and aggressive lymphomas are fast growing. The grade is also referred to as the clinical behaviour of the lymphoma. MCL is an aggressive lymphoma but for some patients it can also behave as an indolent lymphoma.
Staging scan and tests
The scans and tests needed for staging and before treatment can start may include:
- Positron emission tomography (PET) scan
- Computed tomography (CT) scan
- Bone marrow biopsy
- Lumbar puncture & magnetic resonance imaging (MRI) – If lymphoma is suspected in the brain or spinal cord
Patients may also undergo a number of baseline tests prior to any treatment commencing to check organ functions. These are often repeated during and after the treatment has completed to assess whether the treatment has affected the functioning of organs. Sometimes the treatment and follow-up care may need to be adjusted to help manage side effects. These may include:
- Physical examination
- Vital observations (blood pressure, temperature, & pulse rate)
- Heart scan
- Kidney scan
- Breathing tests
- Blood tests
It may take some time for all the necessary biopsies and tests to be done (an average of 1-3 weeks), but it is important for the doctors to have a complete picture of the lymphoma and the general health of the patient in order to make the best treatment decisions
Many of the staging and organ function tests are done again after treatment to check whether the lymphoma treatment has worked and the effect this has had on the body.
It is important to note that lymphoma is what is known as a systemic cancer. It can spread throughout the lymphatic system and nearby tissue and organs. Many patients are diagnosed at an advanced stage and the lymphoma can still be successfully treated. Lymphoma is very unlike advanced stage solid tumour cancers, such as bowel or lung cancer.
Prognosis of mantle cell lymphoma (MCL)
Treatment is usually successful initially in many patients with mantle cell lymphoma (MCL), where most patients respond (either partially or a complete response). However, many people relapse with mantle cell lymphoma (MCL).
Treatment for mantle cell lymphoma (MCL)
Once all the results from the biopsy and the staging scans have been completed, the doctor will review these to decide the best possible treatment for a patient. At some cancer centres, the doctor will also meet with a team of specialists to discuss the best treatment and this is called a multidisciplinary team (MDT) meeting.
Doctors take into consideration many factors about the lymphoma and the patient’s general health to decide when and what treatment is required. This is based on:
- The stage of lymphoma
- Symptoms (including the size and location of the lymphoma)
- How the lymphoma is affecting the body
- Past medical history & general health
- Current physical and mental wellbeing
- Patient preferences
Before treatment is started it is important that adequate information is provided about the treatment that is planned, the possible side effects and what to expect. Education from the cancer nurses prior to receiving treatment, can be extremely helpful and this should include instructions about becoming unwell or needing medical or nursing assistance.
The standard first-line treatment may include:
- R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone)
- R-DHAP (dexamethasone, cisplatin and cytarabine) +/- alternating cycles with R-CHOP
- R-maxi CHOP with alternating cycles of rituximab and cytarabine.
- Hyper-CVAD (part A: cyclophosphamide, doxorubicin, vincristine alternating cycles with part B: methotrexate and cytarabine)
- Autologous stem cell transplant (ASCT)
- Bendamustine and Rituximab
- Clinical trial
Common side effects of treatment
There are many different side effects of the treatment and these are dependent on the treatment that has been given. The treating doctor and/or cancer nurse can explain the specific side effects prior to the treatment. Some of the more common side effects of treatment for MCL (not all) can include:
- Anaemia (low red blood cells that carry oxygen around the body)
- Thrombocytopenia (low platelets that help with clotting and bleeding)
- Neutropenia (low white blood cells that help fight infection)
- Nausea and vomiting
- Fatigue (tiredness or lack of energy)
- Reduced fertility
The medical team, doctor, cancer nurse or pharmacist, should provide information about:
- What treatment will be given
- What are the common and possible side effects for the treatment
- What side effects do you need to report to the medical team
- What are the contact numbers, and where to attend in case of emergency 7 days a week and 24 hours per day
Once treatment has completed, post treatment staging scans are done to review how well the treatment has worked. The scans will show the doctor if there has been a:
- Complete response (CR or no signs of lymphoma remain) or a
- Partial response (PR or there is still lymphoma present, but it has reduced in size)
If all goes well regular follow-up appointments will be made for every 3-6 months to monitor the below:
- Review the effectiveness of the treatment
- Monitor any ongoing side effects from the treatment
- Monitor for any late effects from treatment over time
- Monitor signs of the lymphoma relapsing
These appointments are also important so that the patient can raise any concerns that they may need to discuss with the medical team. A physical examination and blood tests are also standard tests for these appointments. Apart from immediately after treatment to review how the treatment has worked, scans are not usually done unless there is a reason for them. For some patient’s appointments may become less frequent over time
Relapsed or refractory management of mantle cell lymphoma (MCL)
Mantle cell lymphoma will usually respond initially to treatment; however, many patients will relapse (comes back) . The lymphoma can also be refractory, that means the lymphoma either only partially responds or does not respond to standard first line treatment.
When MCL comes back (relapses) or is refractory, further treatment is needed. The second line treatment options may include:
- Clinical trial
- Ibrutinib (ImbruvicaTM)
- Acalabrutinib (Calquence ™)
- Zanubrutinib (Brukinsa™)
- Lenalidomide (RevlimidTM)
- Combination chemotherapy
- Allogeneic stem cell transplant (an option considered for a select few younger, and fitter patients)
Treatment under investigation
There are many treatments that are currently being tested in clinical trials around the world and in Australia for patients with both newly diagnosed and relapsed MCL lymphoma. These can include
- Venetoclax (VenclextaTM)
- Acalabrutinib (Calquence ™)
- Zanubrutinib (BrukinsaTM)
- Bispecific antibody (e.g. mosunetuzumabTM)
- Obinutuzumab (GazyvaTM)
- Umbralisib (P13K inhibitorTM)
- Bortezomib (velcadeTM)
- Chimeric antigen receptor (CAR) T-cell therapy
What happens after treatment?
Sometimes a side effect from treatment may continue or develop months or years after treatment has completed.
This can be a challenging time for many people and some of the common concerns can be related to:
- Mental wellbeing
- Emotional health
- Work, study and social activities
Health and wellbeing
A healthy lifestyle, or some positive lifestyle changes after treatment can be a great help after the treatment has been finished. Making small changes such as eating and increasing fitness can improve health and wellbeing and help the body to recover. There are many self-care strategies that can help during the recovery phase.