Lymphoma—a cancer impacting the lymphatic system—has seen significant advancements in treatment options. One notable method is CAR T-cell therapy, a technique that harnesses our immune system's power to target and eliminate cancer cells specifically.

Let's delve into the details if you're curious about this innovative therapy and its potential benefits in the fight against cancer.

What is CAR T-Cell Therapy?

Immunotherapy has transformed cancer treatment by leveraging the body's immune system against cancer cells. CAR T-cell therapy, short for chimeric antigen receptor T-cell therapy, is an exciting branch of immunotherapy.

This treatment approach involves altering a patient's T cells in order to recognise and attack cancer cells, offering an effective remedy, particularly for some blood cancers and lymphoma. Recently approved in Singapore, this therapy now offers hope for patients who have limited treatment choices.

CAR T-Cell Therapy vs Chemotherapy 

In contrast to traditional chemotherapy, which affects all rapidly dividing cells, CAR T-cell therapy targets only the cancer cells that exhibit specific antigens. This precision potentially reduces the impact on healthy cells, aligning with more personalised treatment strategies and potentially decreasing related side effects.

Potential Conditions Responsive to CAR T-Cell Therapy

According to the Centre for Clinical Haematology, CAR T-cell therapy has demonstrated effectiveness in treating various high-risk blood cancers, including Myeloma, Acute Lymphoblastic Leukaemia (ALL), and Non-Hodgkin Lymphoma (NHL). It is particularly beneficial for patients with relapsed non-Hodgkin lymphoma, providing a crucial alternative after other treatments have not achieved the desired results.

Research is ongoing to determine its effectiveness against other forms of leukaemia and solid tumours, aiming to broaden the application of this targeted treatment.

Understanding CAR T-Cell Therapy Mechanisms

CAR T-cell therapy harnesses the body's immune system to fight cancer more effectively. This treatment modifies a patient's T cells — a crucial component of the immune system — to recognise and destroy cancer cells. The modification involves genetically engineering the T cells to produce special structures called chimeric antigen receptors (CARs), which allow them to latch onto specific cancer cell proteins and kill them.

Immune Receptors and Their Role in Cancer Detection

The immune system detects and neutralises external threats like viruses and bacteria by recognising proteins called antigens on these invaders.

T cells, which are part of the immune system, have receptors that specifically match these antigens. This mechanism allows T cells to bind to and destroy infected or malignant cells. However, cancer cells often evade the immune system by not displaying these antigens clearly.

CAR T-cell therapy overcomes this by providing T cells with engineered receptors that target specific antigens found on cancer cells.

The Role of Chimeric Antigen Receptors (CARs)

CARs are engineered molecules that equip T cells with the ability to target specific proteins on cancer cells. As mentioned, by introducing CARs into a patient’s T cells, these cells are transformed into targeted agents against cancer.

After genetic modification and expansion in the laboratory, these CAR T cells are infused back into the patient. Once inside, they multiply and launch a targeted attack on the lymphoma cells, which are cells displaying the targeted antigens. This approach holds great promise for patients with non-Hodgkin lymphoma that has relapsed or proven resistant to other treatments.

The Comprehensive Process of CAR T-Cell Therapy

The journey of CAR T-cell therapy from lab to clinic involves several critical steps:

• Evaluation: Patients undergo thorough assessments to determine if CAR T-cell therapy is suitable for their specific type of cancer.
• Collection: T cells are collected from the patient’s blood through a process called apheresis, which usually takes a few hours.
• Engineering: These T cells are then genetically modified in a lab to express CARs that target cancer-specific antigens.
• Multiplication: The engineered T cells are cultured in the lab until they multiply into the millions. This growth phase is crucial for ensuring there are enough CAR T cells to effectively combat the cancer.
• Conditioning: Before these cells are returned to the patient, the patient may undergo a mild form of chemotherapy to prepare the body to receive the modified T cells.
• Infusion: The CAR T cells are then infused back into the patient's bloodstream in a procedure similar to a blood transfusion.
• Recovery: Post-infusion, patients are closely monitored for any adverse reactions and the effectiveness of the therapy is evaluated. The recovery of the immune system and the patient's overall health can take several months.

What is One Major Side Effect of CAR T-Cell Therapy

While CAR T-cell therapy offers a new hope for cancer treatment, it comes with potential side effects that patients should be aware of.

Immediate Reactions and Cytokine Release Syndrome (CRS)

A frequent side effect of CAR T-cell therapy is cytokine release syndrome (CRS), characterised by symptoms such as fever, chills, fatigue, and nausea. This occurs when the activated CAR T-cells release cytokines into the bloodstream, triggering an inflammatory response. In severe cases, CRS can lead to more serious complications such as low blood pressure, difficulty breathing, and rapid heartbeat.

Neurological Concerns and Immune System Challenges

Another significant concern with CAR T-cell therapy is its impact on the nervous system, sometimes leading to conditions known as immune effector cell-associated neurotoxicity syndrome (ICANS). Patients may experience confusion, difficulty speaking, tremors, or even seizures.

Long-term Risks and Ongoing Monitoring

Besides the immediate side effects, CAR T-cell therapy may pose long-term risks, such as an increased chance of developing another type of blood cancer.

How Do I Know If I Am Eligible For CAR T-Cell Therapy?

Determining if you are a candidate for CAR T-cell therapy involves a thorough evaluation by healthcare professionals. This innovative therapy is available for specific types of blood cancers under stringent regulations approved by global and local health authorities.

In Singapore, CAR T-cell therapy is available for individuals up to 25 years old with relapsed or refractory acute lymphoblastic leukaemia (ALL) and adults suffering from aggressive forms of B-cell lymphoma who have exhausted other treatment options.

What is the Success Rate of CAR T-Cell Therapy?

CAR T-cell therapy has shown significant success rates in treating certain types of refractory or relapsed lymphomas.

Adults with these conditions have seen complete response rates ranging from 40% to 54% during four-year follow-ups, which are considerably high, especially compared to the 7% response rates from traditional treatments like chemotherapy and autologous transplants.

Similarly, young adults with relapsed or refractory B-acute lymphoblastic leukaemia have experienced complete response rates of 81%, with 76% maintaining this response after 12 months.

Consulting leading cancer doctors in Singapore can provide personalised insights tailored to individual cases.

Where is CAR T-Cell Therapy Available

CAR T-cell therapy was trialled at the National University Cancer Institute, Singapore (NCIS) in April 2023. For those seeking this treatment, it is important to consult healthcare providers for the latest information on where it is actively offered.

Furthermore, it's encouraging to know that some patients have been covered by their health insurance for CAR T-cell therapy. If you're considering this option, it's advisable to speak with your insurance provider to understand the extent of coverage.

Connect with OncoCare For Personalised Guidance

When dealing with lymphoma, understanding your treatment options, including potential disadvantages and complications associated with treatments like CAR T-cell therapy, is crucial. If you or your loved one is navigating the journey of lymphoma treatment in Singapore, consider reaching out to the experienced doctors at OncoCare. Your journey toward lymphoma treatment deserves expert guidance and individualised attention. Speak to the experienced cancer specialists at OncoCare to explore the appropriate cancer treatment pathway for you or your family member. Their knowledge and commitment ensure you receive the care and information you need to make informed decisions. To understand more about how your health insurance may cover lymphoma treatments, visit our insurance enquiries page.

Reach out today to take a step towards effective lymphoma treatment and improved well-being.

“Expert knowledge means better care for cancer”

Written by:

Dr Kevin Tay

MBBS (Singapore)

ABIM Int. Med (USA)

ABIM Med Onc (USA)

FAMS (Medical Oncology)

Citations

Hayes, C. (2020). Cellular immunotherapies for cancer. Irish Journal of Medical Science (1971 -), 190(1), 41–57. https://doi.org/10.1007/s11845-020-02264-w

Singapore General Hospital, National Cancer Centre Singapore (2024). Supporting CAR T-Cell Recipients – What to Look Out For in Primary Care. SingHealth. https://www.singhealth.com.sg/news/defining-med/car-t-cell-primary-care

National Cancer Institute. (2022, March 10). Car T cells: Engineering immune cells to treat cancer. National Cancer Institute. https://www.cancer.gov/about-cancer/treatment/research/car-t-cells

Novartis. (2021, March 9). Novartis receives approval for Kymriah® (TISAGENLECLEUCEL) by Health Sciences Authority as Singapore’s first commercially approved CAR-T therapy. Novartis Singapore. https://www.novartis.com/sg-en/news/media-releases/novartis-receives-approval-kymriah-tisagenlecleucel-health-sciences-authority-singapores-first-commercially-approved-car-t-therapy