Liso-cel shows impressive efficacy in double-refractory CLL/SLL

A groundbreaking clinical trial published in The Lancet demonstrated the remarkable potential of chimeric antigen receptor T-cell (CAR-T) therapy in treating patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Led by Dr. Shuo Ma, the study introduced the use of Liso-cel, a CAR-T therapy, in CLL/SLL treatment.

CLL and SLL are essentially the same disease, characterized by cancerous lymphocytes, and are the most common types of leukemia in adults. Over the past decade, the treatment landscape for CLL/SLL has significantly evolved, with oral targeted therapies replacing conventional immunochemotherapy as the new standard of care.

Despite the effectiveness of targeted therapies, some patients, especially those with high-risk CLL/SLL, become resistant to treatment (double-refractory CLL/SLL), leaving them with limited options and poor outcomes. This highlights the urgent need for better treatments.

In this trial, 117 adult patients with relapsed or refractory CLL or SLL, who had undergone an average of five previous therapies, received a one-time infusion of liso-cel, a CAR-T therapy that enhances T-cells to target and eliminate cancer cells more effectively.

Among the 49 patients with double-refractory CLL/SLL who received a higher dosage of liso-cel, the overall response rate was an impressive 47%, with a complete response and remission rate of 18%. This is a significant improvement compared to the historical rate of zero to 5%, demonstrating the therapy’s efficacy.

The time to response was approximately one month, and the patients who achieved complete response and remission showed no signs of relapse at a 20-month follow-up, indicating the lasting effect of the treatment.

Some transient immune-related adverse effects were observed following liso-cel treatment. More severe (grade 3) adverse events, such as cytokine release syndrome (an acute systemic inflammatory syndrome), occurred in 9% of patients, and advanced neurological events were reported in 18% of patients.

Overall, the study showed that a single infusion of liso-cel can lead to a rapid and durable response in patients with relapsed and refractory CLL or SLL, for whom other treatment options have been exhausted. Dr. Ma believes that CAR-T therapy holds great promise as a future treatment option for patients with CLL/SLL and plans for future studies to compare it with existing standard treatments are being developed.

Source: Northwestern University

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