Chimeric antigen receptor (CAR) T-cell therapy as a treatment option for patients with B-cell lymphomas: Perspectives on the therapeutic potential of Axicabtagene ciloleucel

Abstract

Axicabtagene lisoleucel (Axi-cel) is the second approved gene-alterating cancer treatment and the first in aggressive lymphoma using the “chimeric antigen receptor” (CAR) technology. T-cells from patients were transfected with CARs and reinfused after a lymphodepleting chemotherapy. CAR T-cells are “living drugs” with the ability to persist and expand after a single infusion. Axi-cel is a “second generation” CAR product characterized by the use of a retroviral gene vector transfer and by CD28 as costimulatory domain. In a phase II trial with heavily pretreated patients with aggressive B-cell lymphoma, the overall response rate was 82% with an ongoing complete response rate of 40% after 6 months - with expectations of long-term remissions and cure, even though follow-up data are still limited. There are some prominent side effects like cytokine release syndrome (Grade 3-5: 13%) and neurotoxicity (Grade 3-5: 28%). Novel strategies for prediction, prevention and treatment of these critical side effects are warranted. There are new concepts to enhance the efficacy and prevent resistance in lymphomas. CAR T-cells represent an extremely evolving field with an inestimable potential in general and particularly in aggressive lymphoma. However, we are still learning how to use Axi-cel and other CAR-T cells compounds effectively to optimize the long-term results.