A review of CAR-T cell therapy for CLL

This study reviewed CAR-T cell therapy, a new type of immunotherapy, for chronic lymphocytic leukemia (CLL).

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.

CAR-T therapy may be particularly suited for patients who cannot tolerate or relapse after standard therapy. Previous lines of therapy before CAR-T therapy typically involves targeted therapy, such as ibrutinib (Imbruvica) or idelalisib (Zydelig), or a stem cell transplant.

Most CAR-T cells are engineered to specifically attack the CD19-positive cells (a type of gene active in CLL). This can cause B cell aplasia (low B cell count or absent B cells), which means less protection from infection. However, infusions of immunoglobulins (antibodies) is effective at managing B cell aplasia.

CAR-T cell therapy can result in sustained remission in high-risk CLL patients. One of the first studies reported an overall response rate in 8 of 14 high-risk and heavily pre-treated patients. 4 patients achieved complete remission. All 4 patients maintained complete response at 4 years. Similar results were observed in a second study. 7 out of 8 CLL patients responded to CAR-T cell therapy. Of these, 4 achieved complete remission.

In another study, 20 patients who showed signs of disease progression after a stem cell transplant were treated with CAR-T cell therapy. 5 of these patients had CLL. Of these, 1 CLL patient showed a partial response and 1 achieved complete response.

18 CLL patients no longer responding or relapsing after ibrutinib received CAR-T cell therapy at gradually increasing doses. The overall response rate was 76%. These included 8 partial responses and 5 complete responses. At day 28, 11 of the 13 (85%) responding patients no longer had any detectable leukemia cells in the one marrow.

The most serious side effect associated with CAR-T cell therapy is cytokine-release syndrome. This refers to a specific reaction to some immunotherapies. Symptoms can include fever, low blood pressure, heart complications, breathing problems, and neurologic side effects such as confusion or seizures. Cytokine-release syndrome is usually manageable with appropriate treatment. 

This study concluded that early results with CAR-T cell therapy were promising. Further studies are needed to develop the treatment further and to investigate possible treatment combinations.