- What is immunotherapy?
Immunotherapy, or more specifically cancer immunotherapy, is a type of treatment that helps the body’s immune system fight cancer. The body’s immune system fights infections and disease. It is made up of white blood cells, and the organs and tissues of the lymphatic system. T cells are a type of white blood cell.
- What is CAR-T therapy?
Chimeric Antigen Receptor T cell therapy, or CAR-T therapy, is a type of immunotherapy that modifies a patient’s T cells to better detect and destroy lymphoma.
- How does it work?
CAR-T therapy uses the T cells from the patient’s blood. The T cells are isolated and sent to a special laboratory where they are genetically modified with inactive viruses with a receptor that detect proteins on the surface of a tumour cell. The modified cells, called CAR-Ts, are sent back to the patient’s treatment centre and infused back into the patient. Once in the patient’s body, the CAR-Ts target the cancer cells and the cancer cells are destroyed by the body’s immune system.
- Who is CAR-T for?
Generally speaking, the following patients are eligible for CAR-T therapy:
• Diagnosed with a subtype of lymphoma for which the CAR-T therapy is approved
• Meet regulatory criteria (e.g. relapsed twice and have been previously treated)
• Have tumours that express the specific antigen the therapy targets
• Have normal or limited performance status
• No active infections
• No significant cardiac, neurological or immune dysfunction
However, in addition to subtype and stage, physicians will also assess the patient’s overall health, fitness and circumstance for this treatment. This may include the patient’s comorbidities, the associated ability to withstand the vigorous treatment, and their willingness and ability to travel for treatment
Patients consult with their physician to see if they are medically eligible for CAR-T therapy. This may include submitting medical records to the specialty laboratory that manufactures the CAR-Ts.
- Blood Sampling
Blood is taken from the patient and the white blood cells that contain T cells are isolated and removed in a process called apheresis or leukapheresis. The remaining blood is transfused back to the patient.
TIMELINE: The procedure takes 3–6 hours
- Cell Modification
The T cells are shipped to a designated laboratory where they are genetically modified with inactive viruses into CAR-Ts and expanded. The modified cells are shipped back to the patient’s treatment centre.
TIMELINE: Approximately 2–4 weeks
Patients may be given low-dose chemotherapy called lymphodepleting chemotherapy to reduce their number of immune cells before the CAR-Ts are infused. This helps the CAR-Ts start to grow and multiply within the patient. The patient may receive a bridging therapy to help keep their cancer in check while waiting for CAR-T therapy.
TIMELINE: Approximately 2–14 days before the CAR-T infusion
- CAR-T Infusion
The modified CAR-T cells are infused into the patient at their treatment centre.
TIMELINE: 30–60 minutes
Patients are monitored regularly to see if the CAR-T therapy is effective and for short- and long-term side effects. Patients are advised to stay near their treatment centre for a few weeks. Most short-term side effects can be managed with supportive therapies. These include infections and haematological-related issues, such as prolonged or febrile neutropenia, anaemia and thrombocytopenia. Other more serious and potentially life-threatening side effects include cytokine release syndrome (CRS) and neurotoxicity (now termed IEC-associated neurotoxicity syndrome or ICANS). It is important patients and carers can identify symptoms quickly so they can be treated. The treatment centre will have instructions about what to do and who to contact if symptoms develop.
There are several short- and long-term side effects related to CAR-T therapy. Patients are advised to stay near their treatment centre for a few weeks. Most short-term side effects can be managed with supportive therapies. However other side effects can be more serious and potentially life-threatening and may require treatment in a hospital intensive care unit.
Severe side effects are often the results of the high activity of the immune system brought on by the CAR-T therapy. Immunosuppressive drugs and corticosteroids are used in symptom management, with the goal of curtailing the side effects without removing the CAR-T cells completely. It is important patients and carers can identify symptoms quickly so they can be treated appropriately, especially since the symptoms of some side effects (like neurotoxicity) are the same as those of other medical conditions which are treated very differently.
Cytokine Release Syndrome: As CAR-T cells are released and multiply in the patient’s body, their immune system is highly activated and releases a massive number of inflammatory cytokines into the blood, causing cytokine release syndrome (CSR). This can happen within the first week after infusion or later in some cases. The duration and intensity of CSR can vary. Some patients only experience mild flu-like symptoms while others have high fevers, hypoxia (oxygen deficiency), low blood pressure and multi-organ toxicity.
Neurotoxicity (now termed IEC-associated neurotoxicity syndrome or ICANS): IEC refers to Immune Effector Cells. The CAR-T cells can have an effect on the patient’s brain, which can cause confusion, agitation and a lack of awareness. Patients may experience headaches, difficulties with written or spoken language, anxiety and occasional seizures. Neurotoxicity can occur with or without cytokine release syndrome. If a patient also experiences CRS, neurologic symptoms more commonly occur after CRS. It is reversible in most cases, but in rare cases, cerebral oedema associated with neurotoxicity may develop, which is potentially fatal.
Macrophage-Activation Syndrome: Macrophage-activation syndrome is the severe inflammation of the immune system, which can cause multi-organ failure.
Febrile Neutropenia: Febrile neutropenia is an abnormal decrease in the number of certain white blood cells in the blood coupled with fever.
B Cell Aplasia: B cell aplasia is a low number of B cells or no B cells. This is a common lasting side effect of CAR-T.
Anaemia: Anaemia is a condition in which the number of red blood cells is below normal.
Thrombocytopenia: Thrombocytopenia is a decrease in the number of platelets in the blood.
Hypogammaglobulinemia: Hypogammaglobulinemia is a reduction in all types of gamma globulins, including antibodies that help fight infection.
To view approved CAR-T therapies by country, click here.
To find out the latest news on CAR-T, please click here.
Also review the CAR-T report here.