CAR-T cell therapy and infection risk

This study examined infection risk in leukemia and lymphoma patients treated with CAR-T cell therapy, a new type of immunotherapy. Researchers reported that infection rates were comparable to other salvage therapies. 

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 cancer 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 attack cancer cells. Because CAR-T cells stay in the body long after treatment, they may be particularly suited for patients at high-risk of relapse.

CAR-T cell therapy has been associated with high response rates in leukemia and lymphoma patients. These include acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and non-Hodgkin lymphoma (NHL). However, more studies are needed to examine the risk of infection. Many patients receiving CAR-T cell therapy have poor immune function due to their disease and previous lines of treatments, which increases the risk of infection.

The aim of this study was to examine infection risk in patients treated with CAR-T cell therapy.

A total of 133 patients with relapsed or refractory (did not respond to treatment) disease were included. 47 were ALL patients, 24 were CLL patients, and 62 were NHL patients. Before the study, patients had undergone an average of 4 lines of treatment. All patients then received CAR-T cell therapy. The CAR-T cells were engineered to specifically attack the CD19-positive cells (a type of gene active in cancer growth). Infection rates were recorded during the first 90 days after treatment.

43 infections were recorded in 30 patients (23%) within 28 days after treatment. Overall, there were 1.19 infections for every 100 days at risk. The lowest rate of infection was observed between days 29 to 90 (0.67 infections). The first infection occurred after an average of 6 days after the end of CAR-T cell therapy.

Between day 0 and 90 after CAR-T cell therapy, 33 out of 66 infections (50%) in 23 patients were mild or moderate infections. 27 infections (41%) in 19 patients were considered severe. 4 infections (6%) in 3 patients were life-threatening. Infection was a cause or contributing factor of death in 2 patients. Overall, the incidence of infection was comparable to those observed with other immunotherapies or chemotherapies.

Infection risk within 28 days was significantly higher for ALL patients, patients with 4 or more prior lines of therapy, and those receiving high-dose CAR-T cell therapy.

40 patients showed signs of cytokine release syndrome (a specific reaction to some immunotherapies). 28 patients developed both an infection and cytokine release syndrome. Patients with more severe cytokine release syndrome were at increased risk of developing an infection. 

This study concluded that the incidence of infection with CAR-T cell therapy is comparable to those observed with other immunotherapies or chemotherapies. Modifications to the treatment regime to reduce the risk of cytokine release syndrome can also reduce the risk of infection. 

Further studies are needed to confirm these results.