Chimeric Antigen Receptor (CAR) T-cell Therapy

Chimeric Antigen Receptor (CAR) T-cell Therapy is a form of immunotherapy wherein T-cells are extracted from the patient's blood and subsequently modified within a laboratory setting to enable them to identify and eradicate specific cancer cells. Usually, T-cells (T-lymphocytes, a type of white blood cell within our immune system) possess the capability to identify abnormal cells or cells infected by viruses within the body and subsequently eliminate these threats. However, T-cells may occasionally fail to recognize or eliminate cancer cells.

In Chimeric Antigen Receptor (CAR) T-cell Therapy, the modified T-cells are reintroduced into the patient's bloodstream. Upon reinfusion into the patient's body, these modified T-cells can identify cancer cells and initiate their destruction by leveraging the body's innate immune response. Singapore stands as the first country in Southeast Asia to offer this treatment.

CAR T-cell Therapy offers cancer patients a potential life saving treatment option especially when their conditon does not respond to standard chemotherapy, targeted therapy or bone marrow transplantation.

CAR T-cell Therapy is very effective in the following conditions:

• Relapsed aggressive forms of Acute Lymphoblastic Leukemia (ALL).
• Relapse of Non-Hodgkin Lymphoma such as Diffuse Large B-cell Lymphoma (DLBCL).
• In cancer therapeutic interventions where a minimum of two prior cancer treatment regimens have failed to produce the desired outcomes.

Individuals who are eligible for CAR T-cell Therapy are as follows:

• Children and young adult patients from 2 to 25 years old with B-cell Acute Lymphoblastic Leukemia (ALL) that is resistant, and where a relapse has occurred subsequently or post-transplant.
• Adults with Diffuse Large B-cell Lymphoma (DLBCL) who have not benefited from at least two types of standard treatment.

Individuals with the following clinical conditions are excluded from CAR T-cell Therapy:

• Intracranial hypertension or unconsciousness.
• Respiratory failure.
• Disseminated intravascular coagulation.
• Patients with hemato-sepsis or uncontrolled active infection.

Patients will initially undergo screening and a series of tests to determine the suitability of CAR T-cell Therapy for their disease and assess their fitness for treatment.

White blood cells, including T-cells, will be extracted from the patient's blood using a procedure known as leukapheresis. During this process, two intravenous infusion (IV) lines will be inserted into the patient: one to extract blood for the separation of white blood cells, including T-cells, and the other to return the remaining blood components to the patient's body.

Patients will be comfortably positioned either lying down or seated on a reclining chair during the procedure.

Following the extraction of white blood cells, T-cells will be isolated and transported to the laboratory for modification. This involves introducing the specific Chimeric Antigen Receptor (CAR) gene to the T-cells, transforming them into CAR T-cells. Subsequently, these cells will undergo proliferation and multiplication within the laboratory setting.

Typically, it takes 2 to 3 weeks to generate a sufficient quantity of CAR T-cells necessary for CAR T-cell Therapy.

Upon successful production of an adequate number of CAR T-cells, the product will be delivered back to the hospital for infusion into the patient.

Several days before the CAR T-cell infusion, the patient may receive chemotherapy to reduce the number of other immune cells in the body, priming the body to receive the CAR T-cells effectively. This facilitates the activation of the newly infused CAR T-cells to combat the cancer cells. The chemotherapy regimen is generally less intensive to ensure the presence of residual cancer cells for the CAR T-cells to effectively target.

As the CAR T-cells engage with cancer cells within the body, their population will increase, destroying additional cancer cells.

Patients undergoing CAR T-cell Therapy will undergo an initial recovery period lasting approximately 6 to 8 weeks. Throughout this phase, patients will be closely monitored for any adverse effects and evaluated for treatment response.

Recovery usually spans 2 to 3 months following the CAR T-cell infusion. Patients will be hospitalized for the initial 2 to 3 weeks to recuperate from any chemotherapy-related side effects before being discharged.

Upon discharge, patients will need to attend routine outpatient appointments to monitor treatment-related side effects and clinical responses.

A prevalent side effect of CAR T-cell Therapy is Cytokine Release Syndrome (CRS), a multisystemic disorder resulting from the effects of CAR T-cells and the subsequent elimination of cancer cells. Symptoms of CRS include:

• High fever and chills
• Difficulty breathing
• Nausea, vomiting, and/or diarrhoea
• Dizziness and lightheadedness
• Headaches
• Rapid heartbeat
• Fatigue
• Muscle and/or joint pain

While CRS may manifest weeks after infusion, it most commonly occurs within two weeks following the procedure. The severity of CRS does not necessarily correlate with the response to CAR T-cell Therapy.

Another frequently encountered side effect is immune effector cell-associated neurotoxicity syndrome (ICANS), which impacts the patient's central nervous system.

Both CRS and ICANS are well-recognized side effects that can be effectively managed by a proficient clinical care team.