Evaluating the long-term effectiveness and safety of tandem CAR T-cell therapy for patients with relapsed/refractory non-Hodgkin lymphoma.

This study investigated the long-term safety and effectiveness of tandem chimeric antigen receptor (tCAR) T-cell therapy for patients with relapsed or refractory (r/r) non-Hodgkin lymphoma (NHL). The data showed that tCAR T-cell therapy resulted in long-term remission rates with manageable side effects for these patients.

NHL is cancer that starts in white blood cells called lymphocytes, which are part of the body’s immune system. Standard treatment for NHL is chemotherapy plus immunotherapy. A high number of patients with NHL experience relapse (the tumor grows after treatment) or are refractory (not responsive to the treatment) to standard treatment. For these patients, treatment options are limited.

CAR T-cell therapy is one option for these patients. T cells are a type of white blood cell that is involved in destroying cancer cells. Cells have various molecules on their surfaces. Each T cell has receptors (proteins) that can recognize a specific target molecule. The T cells will destroy any cells that have the target. CAR T-cell treatment involves removing a patient’s own T cells and modifying them to have receptors designed in the laboratory. Most of these designed receptors target CD19, which is a protein found on B cells in NHL.

However, some patients will relapse after CAR T-cell treatment. When CD19 is targeted, lymphoma cells can evolve over time to have fewer CD19 proteins on their surface. When this happens, the CAR T-cell treatment will no longer be effective. One way to prevent this is to design receptors that can recognize two target molecules. tCAR7 T-cells can recognize both CD19 and CD20, two molecules that are found on B lymphoma cells. However, there are few studies investigating the long-term safety and effectiveness of tCAR7 T-cell treatment for patients with r/r NHL.

The study involved 87 patients with r/r NHL who had positive CD19 and CD20 receptors on cancer cells. All patients received tCAR7 T-cells after chemotherapy. The average follow-up time was 27.7 months.

Overall, 78% of the patients responded to the treatment. The complete response rate (complete disappearance of cancer cells) was 70%. The partial response rate (partial disappearance of cancer cells) was 8%.

After 6 months, 80% of the patients were in remission and after 12 months, 76% of the patients were in remission. After 27.7 months, 60% of patients were still in remission.

The average survival without progression or cancer worsening was 27.6 months. After 12 months, 61% of the patients were alive without progression or cancer worsening.

70% of the patients experienced cytokine release syndrome (CRS). 60% had mild CRS and 10% had severe CRS. CRS is a side effect of CAR T-cell therapy caused by the immune system becoming highly active. CRS can cause fever, nausea, skin rash, an increase in heartbeat, low blood pressure, and trouble breathing. The other most common side effects were low white blood cells counts, low platelet counts, and fever.

This study concluded that tCAR7 T-cell therapy resulted in long-term remission rates in patients with r/r NHL.

The sample size of this study was small. This study was conducted only at a single institution in China. Larger studies with a longer follow-up are needed to confirm the effectiveness of combined T-cell therapy.