Chemotherapy Regimens For Mantle Cell Lymphoma

Non-hodgkin's lymphoma is the 13th most common cause of death from cancer. During the period from 2017 to 2019, Non-Hodgkin's lymphoma led to the deaths of 4,908 people in the UK.¹ Mantle Cell Lymphoma (MCL) is a rarer form of non-hodgkin's lymphoma which makes up around 5% of all non-hodgkin's cancers. Non-hodgkin's lymphoma is a cancer of the lymphatic system, made up of glands and vessels that help transport important immune cells throughout the body. MCL is most commonly diagnosed in patients aged 60-70 years and is more prevalent in men. Specifically, MCL affects the B cells in your immune system, cells which help produce antibodies to fight off any disease-causing agents your body may come in contact with. 

MCL causes many complications in patients, often depending on the area of the body affected by the cancer. For example, it can cause gastrointestinal (GI) complications hindering the body's digestive system and potentially causing bleeding or blockage. It can cause splenic rupture, which results in a medical emergency due to internal bleeding. Additionally, the most aggressive form of the disease can cause tumours to break down which releases toxic substances into the bloodstream that can severely damage the kidneys and result in critical conditions. Unfortunately, MCL remains difficult to treat with fairly low survival rates of around 1.8 to 9.4 years.² However, there are some therapies available to help reduce MCL. In particular, chemoimmunotherapy is a common treatment strategy used in this diagnosis. In this article, we will discuss and explain the treatment regimes for this rare form of cancer. 

Understanding chemotherapy for mantle cell lymphoma 

Chemotherapy, a critical treatment for MCL stops the fast growth and spread of cancer cells. These drugs interfere with the DNA in the cancer cells to destroy them. However, they not only destroy harmful cells but also damage healthy cells during the process of DNA creation which causes unpleasant side effects in the body. Chemotherapy usually requires multiple treatment cycles to be effective at destroying all the cancer cells. In addition, side effects such as nausea, fatigue, hair loss and infection can occur.³ 

When treating MCL, doctors will commonly use combination chemotherapy, a type of treatment which involves multiple drugs with differing mechanisms of action to each other. This treatment helps to reduce the chances of cancer cells growing resistant to treatment and spreading. 

Chemotherapy regimens for MCL

Chemotherapy regimens are used in treating MCL; this involves carefully timing the treatment cycles to ensure the maximum efficiency of cancer cell destruction while ensuring minimal damage is caused to healthy cells. Regimens utilise different drug combinations to target various stages of the cell cycle process through which cells divide and grow. These help to reduce the risk of treatment resistance and potentially life-threatening side effects.⁴ The two most common chemotherapy regimens utilised in MCL are R-CHOP and R-HyperCVAD.²

R-CHOP consists of the drugs rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone:

• Rituximab is a monoclonal antibody meaning it can target a protein called CD20 on the surface of lymphoma cells. It adheres to these proteins and marks them to be destroyed 
• Doxorubicin and Vincristine are chemotherapy drugs known as antimicrotubular agents, destroying the microtubules in cancer cells and limiting their division and growth
• Cyclophosphamide is an alkylating agent chemotherapy drug, which means it forms highly reactive groups that attach to DNA and block the replication of cancer cells
• Prednisolone, the final component, is a steroid. It helps reduce patients' feelings of sickness and decreases the body's immune response to stop allergic reactions to the drug rituximab.⁵ 

R-CHOP treatment typically occurs in cycles, usually every three weeks. On Day 1 of each cycle, the patient receives several medications through a drip into their bloodstream, including rituximab, cyclophosphamide, doxorubicin, and vincristine. Prednisolone tablets are taken before rituximab on Day 1 and continued on Days 2 to 5. After Day 5, the patients are required to have a break from treatment until the next cycle begins.⁵

R-HyperCVAD consists of the drugs: Cyclophosphamide (C), Vincristine Sulfate (V), Doxorubicin Hydrochloride (Adriamycin, A) and Dexamethasone (D). It is administered as a hyperfractionated therapy, meaning the total daily dose is divided into multiple doses during the day.⁶ 

• Cyclophosphamide is given at very high doses in a divided manner
• Vincristine sulphate, given intravenously
• Doxorubicin hydrochloride, an antibiotic administered intravenously
• Dexamethasone, a steroid which helps to reduce any inflammation caused and to suppress the effects of the immune system⁶ 

Additionally, R-HyperCVAD is given in alternating cycles switching between the medications- methotrexate and cytarabine. 

Current studies and research into MCL chemotherapy regimens

In the study of mantle cell lymphoma (MCL) using the R-CHOP regimen, researchers found that the median time patients remained free from treatment failure was about 34 months. For those who achieved complete remission, this time was longer at 37 months compared to 14 months for others. The overall survival rate for the entire group was approximately 7.9 years, with younger patients under 65 years showing better outcomes. This regimen, consisting of four cycles of R-CHOP followed by a single administration of 90Y-ibritumomab tiuxetan, proved effective in prolonging the time before the disease worsened.⁷

Additionally, in a recent study on mantle cell lymphoma (MCL), R-HyperCVAD treatment was followed by an autologous stem-cell transplant (ASCT). The study included 33 fit patients, where 78.8% achieved complete remission after receiving two cycles of R-HyperCVAD. 

• Among those eligible for ASCT, the median progression-free survival (PFS) was impressive at 114 months (9.4 years), compared to 21 months (1.8 years) for patients who did not undergo transplant
• The median progression-free survival for the entire group was 73 months (6.08 years), indicating a significant extension in disease-free survival
• Median overall survival (OS) was notably longer in patients who underwent ASCT, reaching 123 months (10.25 years), compared to 31 months (2.6 years) for those who did not receive the transplant

These findings highlight R-HyperCVAD followed by ASCT as a promising treatment option for achieving prolonged remission and survival in MCL patients.⁸

R-CHOP and R-HyperCVAD are both chemotherapy regimens used for MCL but they differ in intensity and approach. R-CHOP is less intensive, typically involving fewer cycles and no stem-cell transplant. At the same time, R-HyperCVAD is more aggressive with multiple cycles and often includes autologous stem-cell transplant, leading to higher remission rates and potentially longer survival outcomes.

Personal testimonial from a patient in remission from MCL 

In 2000, Bob's life took a turn when he noticed some lumps on his chin and began feeling unwell. After tests, he received the shocking news: mantle cell lymphoma. Processing the diagnosis was tough indeed and sharing it with loved ones brought mixed reactions. Some were incredibly supportive, while others seemed unsure how to respond. Bob credits his trusted medical team for guiding him through chemotherapy and a stem cell transplant, which became pivotal moments in his journey to recovery, despite the challenges along the way.

Today, Bob is grateful to be in complete remission and enjoys an active life, made possible by the exceptional care he received. He is passionate about giving back to the lymphoma community through his work with the Lymphoma Research Foundation. His message to others facing similar battles is one of hope and resilience, underscored by his 19-year journey as a survivor.⁹

FAQs

What is mantle cell lymphoma (MCL)? 

Mantle Cell Lymphoma (MCL) is a rare type of non-Hodgkin's lymphoma, accounting for about 5% of all cases. It primarily affects B cells in the immune system, which normally help fight infections. MCL is more common in men aged 60-70 years and can be aggressive, impacting various parts of the body.

What is chemotherapy's role in treating MCL? 

Chemotherapy is a key treatment for MCL, aiming to stop the rapid growth of cancer cells. Chemotherapy drugs interfere with cancer cells' DNA, preventing them from dividing and spreading. However, these drugs can also affect healthy cells, leading to side effects like nausea, fatigue and increased susceptibility to infections.

What are R-CHOP and R-HyperCVAD chemotherapy regimens? 

R-CHOP includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. It is given in cycles, targeting lymphoma cells with monoclonal antibodies and chemotherapy drugs. R-HyperCVAD is more intensive, involving multiple drugs like cyclophosphamide, vincristine, doxorubicin, and dexamethasone, often alternating with methotrexate or cytarabine.

What are the survival outcomes with R-CHOP and R-HyperCVAD for MCL? 

Studies show that R-CHOP can extend the time before treatment failure and improve survival rates in MCL patients. Meanwhile, R-HyperCVAD followed by autologous stem-cell transplant (ASCT) has shown promising results, with higher rates of complete remission and longer progression-free survival compared to non-transplant options. These treatments continue to be evaluated to improve outcomes for individuals with MCL.

Summary

Mantle Cell Lymphoma (MCL) is a rare type of non-Hodgkin's lymphoma affecting B cells in the immune system, primarily found in older men. Treatment often involves chemotherapy, with regimens like R-CHOP and R-HyperCVAD, which aim to stop cancer cell growth. R-CHOP is less intense, given in cycles to target lymphoma cells, while R-HyperCVAD is more aggressive and may include stem cell transplants for better outcomes. Both regimens have been shown to extend the survival rates and improve remission rates in MCL patients, underscoring ongoing efforts to refine treatment strategies and enhance patient outcomes.