The use of CAR-T cell therapy for AML

This study reviewed the use of CAR-T cell therapy, a new type of immunotherapy, for acute myeloid leukemia (ALL).

Chemotherapy is often the first-line treatment for AML. In cases of a relapse (return of the disease), alternative treatment options are usually explored. This is because many patients develop a resistance to standard therapy over time (refractory disease).

Chimeric antigen receptor (CAR) T-cell therapy helps the immune system to fight cancer cells. In this treatment, immune cells (the T-cells) are removed from the blood. The T-cells are then genetically modified in a laboratory to produce CAR. CAR is a protein that helps the T-cells recognize leukemia cells as something to attack. After the T-cells are modified, they are CAR-T cells. The CAR-T cells are reintroduced into the patient and will then attack AML cells. Because CAR-T cells stay in the body long after treatment, they may be particularly suited for patients at high-risk of relapse.

A number of studies have reported high long-term complete remission rates in patients with relapsed or refractory acute lymphoblastic leukemia (ALL). In recent years, studies have focused on translating CAR-T cell therapy for AML. The aim of this study was to review the use of CAR-T cell therapy for AML.

One possible side effect of CAR-T cell therapy is cytokine-release syndrome. This refers to a specific reaction to some immunotherapies. Symptoms can include fever, nausea, chills, low blood pressure, fast heart rate, low energy, headache, rash, sore throat, and difficulty breathing. A number of clinical studies have shown rapid relief with the immune system suppressant tocilizumab (Actemra) plus a steroid drug.

A complication known as ‘on target/off tumor toxicity’ occurs when the CAR-T cells attack the correct type of protein but the tissue does not contain leukemia cells. Symptoms range from mild (fever, nausea) to severe (organ failure, heart rate abnormalities, death). ‘Suicide genes’ let doctors kill off engineered T cells in emergencies which threaten patient survival. The effect takes place within hours and helps control ‘on target/off tumor toxicity’.

Early results are showing high effectiveness of CAR-T cell therapy in AML patients. However, some patients relapse after CAR-T cell therapy. This can be due to a number of leukemia cells not being recognized by a given CAR. Engineered cells known as ‘TRUCKS’ can help attract an immune cell response toward those leukemia cells invisible to CAR-T cells. Researchers have also identified methods that may increase the effectiveness of CAR-T cell therapy. Engineering CAR-T cells to attack CD33 as well as CD19-positive cells (types of proteins active in acute leukemia) may offer better cancer control. This is known as dual-signaling CAR-T cells. 

Research groups have developed a number of strategies to help improve the use of CAR-T cell therapy for AML. Authors concluded that CAR-T cell therapy has potential as a new therapeutic approach for high-risk AML.