Dr Porter on the Future of CAR T-Cell Therapy in Relapsed/Refractory CLL

David L. Porter, MD, director, Cell Therapy and Transplant, Jodi Fisher Horowitz Professor in Leukemia Care Excellence, Perelman School of Medicine, Penn Medicine, discusses the future of CAR T-cell therapy in patients with relapsed/refractory chronic lymphocytic leukemia (CLL).

CAR T-cell therapy in CLL holds promising potential, especially when considering innovative combinations with existing treatments such as ibrutinib (Imbruvica), Porter begins. In a phase 1 clinical trial (NCT02640209), patients previously treated with ibrutinib who did not achieve complete remission (CR), were administered CAR T-cell therapy, he says. The outcomes were remarkably encouraging, with 44% (95% CI, 23%-67%) of patients attaining CR within 3 months, Porter explains. Notably, advanced testing revealed undetectable levels of minimal residual disease in most patients, hinting at a broader scope of CAR T-cell therapy benefit beyond conventional CR measurements, according to Porter. Furthermore, many patients sustained these responses over the long term, indicating the therapy’s enduring efficacy, he elucidates.

The prospect of refining therapies to enhance patient outcomes fuels considerable excitement, Porter continues. Although CAR T-cell therapy has profound efficacy in responsive patients, efforts are underway to extend its benefits to a broader patient population, he explains. Various strategies are being explored, including the use of novel CAR constructs fortified with additional cytokines to amplify CAR T-cell activity, Porter reports. Additionally, studies investigating combination therapies, such as pairing CAR T cells with BTK inhibitors or employing innovative approaches to select more potent CAR T cells, are underway, Porter notes.

Innovations such as allogeneic CAR T-cell therapy and the exploration of alternative CAR-modified cell types, such as natural killer cells, present additional avenues for CLL management, he expands. These approaches offer unique advantages and are poised to contribute significantly to the evolution of cell-based therapies, Porter says. Advancements in CLL-specific CAR T-cell research hold implications beyond this specific disease, shaping the broader trajectory of CAR T-cell therapy development, he states. With rapid progress characterizing the field, the future of CAR T-cell therapy appears increasingly promising, continually advancing toward more effective and accessible treatment modalities, Porter concludes.