How Does CAR T-Cell Immunotherapy Work?

CAR T-cell immunotherapy is a kind of targeted therapy used to treat blood cancers such as leukemias, lymphomas and multiple myeloma. CAR T-cell immunotherapy involves genetic modification of the patient’s own immune cells (T-cells) to enable them to identify and kill the cancer cells. It is usually used to treat cancers that are refractory or have relapsed after other treatments such as chemotherapy.

Leukemia is a cancer in which white blood cell forming stem cells in the bone marrow become abnormal and grow uncontrollably. Lymphoma is a cancer that affects mature lymphocytes, a type of immune cells that fight infection and are part of the lymphatic system. Multiple myeloma is a cancer of plasma cells, a type of mature lymphocytes that produce antibodies against specific pathogens.

Lymphocytes are part of the acquired immune system and are of three main types, T-cells, B-cells and natural killer cells. B-cells produce antibodies to fight pathogens, while T-cells directly kill pathogens as well as abnormal cells in the body, including cancer cells. CAR T-cell immunotherapy is a biological product containing T-cells genetically modified to identify and kill cancer cells.

In CAR T-cell immunotherapy T-cells are harvested from the patient’s blood. These T-cells (autologous) are then genetically re-engineered in the laboratory by adding a gene that produces proteins on the T-cell membrane surfaces, known as chimeric antigen receptors (CARs), which will identify and bind to specific proteins (antigens) that are present on the surface of cancer cells.

Millions of these modified CAR T-cells are then grown in the lab, washed, purified, suspended in a solution, and frozen. The solution is thawed before use, and intravenously infused back into the patient. Before infusion, the patient may be given chemotherapy to reduce other immune cells in the body, to give the CAR T-cells a better chance to get activated. The CAR T-cells continue to multiply in the body, recognize the cancer cells by the specific antigens and kill them. 

CAR T-cell therapy is an individualized treatment and cancer-specific. Only the patient’s own T-cells are used, and cells from donor blood cannot be used. So far, the available CAR T-cell therapies target one of two antigens present on B-cells, CD19 and B-cell maturation antigen (BCMA).

CAR T-cell immunotherapy is a relatively recent treatment, but has been found to help in keeping cancer in remission for years. The first CAR T-cell immunotherapy was approved by the FDA in 2017 to treat acute lymphoblastic leukemia (ALL) in children. Since then, the FDA has approved 5 more CAR T-cell immunotherapies for the treatment of leukemias, lymphomas and multiple myeloma.

CAR T-cell immunotherapy is a suspension administered as an intravenous solution. CAR T-cell immunotherapy is approved by the FDA for the treatment of the following:

• Tisagenlecleucel (Kymriah):
  • Refractory or relapsed B-cell acute lymphoblastic leukemia (ALL) in children and adults
  • Refractory or relapsed large B-cell lymphoma in adults, including diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma and DLBCL arising from follicular lymphoma
  • Refractory or relapsed follicular lymphoma in adults (continued approval for this indication will be based on verification of clinical benefit in clinical trials)
• Axicabtagene ciloleucel (Yescarta):
  • Refractory or relapsed large B-cell lymphoma in adults, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma
  • Refractory or relapsed follicular lymphoma in adults (continued approval for this indication will be based on verification of clinical benefit in clinical trials)
• Brexucabtagene autoleucel (Tecartus):
  • Refractory or relapsed mantle cell lymphoma in adults (continued approval for this indication will be based on verification of clinical benefit in clinical trials)
  • Refractory or relapsed B-cell precursor acute lymphoblastic leukemia (ALL) in adults
• Lisocabtagene maraleucel (Breyanzi):
  • Refractory or relapsed large B-cell lymphoma in adults, including diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, DLBCL arising from indolent lymphoma, and follicular lymphoma grade 3B
  • Refractory or relapsed chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia in adults (continued approval for this indication will be based on verification of clinical benefit in clinical trials)
  • Refractory or relapsed follicular lymphoma in adults (continued approval for this indication will be based on verification of clinical benefit in clinical trials)
  • Refractory or relapsed mantle cell lymphoma in adults
• Idecabtagene vicleucel (Abecma):
  • Refractory or relapsed multiple myeloma in adults
• Ciltacabtagene autoleucel (Carvykti):
  • Refractory or relapsed multiple myeloma in adults

Some of the common side effects of CAR T-cell immunotherapy include the following:

• Cytokine release syndrome (CRS)
• Low antibody/immunoglobulin levels (hypogammaglobulinemia)
• Abnormal immune response disorders (hemophagocytic lymphohistiocytosis/macrophage activation syndrome)
• Early mortality
• High temperature (pyrexia)
• Fatigue
• Swelling (edema)
• Chills
• Hypersensitivity reactions
• Decrease in blood cells including:
• Lymphocytes (lymphocytopenia)
• White blood cells (leukopenia)
• Neutrophils (neutropenia)
• Platelets (thrombocytopenia)
• Red cells (anemia)
• Fever due to low neutrophils (febrile neutropenia)
• Blood clotting disorder (coagulopathy)
• Blood clots in blood vessels (thrombosis)
• Decrease in blood fibrinogen, a protein necessary for blood clotting
• Infections including:
  • Upper respiratory tract
  • Viral
  • Bacterial
  • Fungal
  • Pneumonia
  • Sepsis
• Decrease in hemoglobin
• Decrease in phosphate (hypophosphatemia)
• Decrease in sodium (hyponatremia)
• Low calcium in blood (hypocalcemia)
• Low potassium in blood (hypokalemia)
• High ferritin levels in blood (hyperferritinemia)
• Increase in triglycerides
• Increase in liver enzyme alanine aminotransferase (ALT)
• Increase in aspartate aminotransferase (AST)
• Increase in gamma-glutamyltransferase (GGT)
• Increase in bilirubin levels (hyperbilirubinemia)
• High blood sugar (hyperglycemia)
• Increase in blood uric acid
• Rapid heart rate (tachycardia)
• Slow heart rate (bradycardia)
• Irregular heart rhythms (non-ventricular arrhythmias)
• Diarrhea
• Nausea
• Vomiting
• Constipation
• Abdominal pain
• Oral pain
• Dry mouth
• Swallowing difficulties (dysphagia)
• Musculoskeletal pain
• Joint pain (arthralgia)
• Headache
• Nerve toxicities including:
• Brain disorder (encephalopathy)
• Nerve damage (neuropathy)
• Peripheral neuropathy
• Dizziness
• Sleep disorder
• Insomnia
• Delirium
• Anxiety
• Language disorder (aphasia)
• Motor dysfunction
• Tremor
• Reduced appetite
• Low blood pressure (hypotension)
• High blood pressure (hypertension)
• Hemorrhage
• Shortness of breath (dyspnea)
• Low oxygen saturation (hypoxia)
• Cough
• Pulmonary edema
• Fluid around lungs (pleural effusion)
• Mouth and throat pain (oropharyngeal pain)
• Rapid breathing (tachypnea)
• Nasal congestion
• Kidney insufficiency
• Reduced urine output
• Kidney failure
• Rash
• Secondary malignancies

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of CAR T-cell immunotherapy include:

• Abecma
• axicabtagene ciloleucel
• brexucabtagene autoleucel
• Breyanzi
• Carvykti
• ciltacabtagene autoleucel
• idecabtagene vicleucel
• Kymriah
• lisocabtagene maraleucel
• obecabtagene autoleucel
• Tecartus
• tisagenlecleucel
• Yescarta