CAR-T cell therapy: A new type of immunotherapy for relapsed ALL?

This study examined the safety and effectiveness of CAR-T cell therapy, a new type of immunotherapy, for relapsed acute lymphoblastic leukemia (ALL). Authors reported high remission rates with CAR-T cell therapy, even for patients with several relapses or for whom stem cell transplantation had failed.

Chemotherapy is often the first-line treatment for ALL. 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.

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 ALL 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 ALL cells. Because CAR-T cells stay in the body long after treatment, they may be particularly suited for patients with a high-risk relapse or multiple relapses.

The aim of this study was to examine the effects of CAR-T cell therapy in relapsed ALL patients.

30 children and adults with relapsed ALL were included in this study. 26 patients had the most common subtype of ALL (called B-cell ALL). These patients were in their first to fourth relapse. 3 further patients with B-cell ALL were no longer responding to primary treatment. One patient had T-cell ALL, a less common form of ALL. 18 of the patients had relapsed disease after undergoing stem cell transplantation. All patients were treated with CAR-T cell therapy. The CAR-T cells were engineered to specifically attack the CD19-positive cells (a protein active in ALL).

At 1 month, 90% of patients were in morphologic complete remission (normal blood cell counts). A complete remission was observed in 2 of the 3 patients who were no longer responding to primary treatment. 15 patients who had undergone a stem cell transplant reached complete remission. 22  patients were negative for minimal residual disease (small number of leukemia cells that remain after treatment).

Sustained remission at 6 months was achieved in 67% of patients. Of the 19 patients who remained in remission, 15 received no further therapy and 4 patients withdrew from the study to receive other therapy. The 6-month overall survival rate (proportion who have not died from any cause since treatment) was 78%.

CAR-T cells were detectable in the blood for up to 11 months after treatment. The probability of detecting CAR-T cells at 6 months was 68%. The probability that a patient would show an absence of CD19-positive ALL cells at 6 months was 73%. In the patient with the longest remission (2 years), an absence of CD19-positive ALL cells continued for a year after CAR-T cells were no longer detectable in the blood.

All patients showed signs of cytokine-release syndrome. This is a 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. 27% of patients had severe cytokine-release syndrome, which started on average 1 day after treatment. All patients recovered fully.

Researchers concluded that CAR-T cell therapy was effective in treating relapsed ALL. Authors reported high remission rates even for patients with several relapses or for whom stem cell transplantation had failed. 

Larger studies are needed to confirm these preliminary results.