Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma

Abstract

Adoptive T-cell immunotherapy is a rapidly growing field and is shifting the paradigm of clinical cancer treatment. Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor T-cell therapy that was initially developed at the National Cancer Institute and has recently been commercially approved by the US Food and Drug Administration for relapsed or refractory aggressive non-Hodgkin's lymphomas including diffuse large B-cell lymphoma and its variants. The ZUMA-1 Phase I and II clinical trials formed the basis of the US Food and Drug Administration approval of this product, and we discuss the particulars of the clinical trials and the pharmacology of axi-cel. In addition, we review the CD19 chimeric antigen receptor T-specific toxicities of cytokine release syndrome and neurotoxicity, which remain the challenges to the safe delivery of this important therapy for aggressive B-cell lymphomas with poor prognosis.

Keywords: CAR T; axicabtagene ciloleucel; immunotherapy; non-Hodgkin’s lymphoma.

Figure 1

Comparative serum concentrations of chemotherapy and CAR T-cell expansion. Notes: Traditional cytoreductive chemotherapy has the greatest impact immediately following initiation; however, it is short-lived, requiring multiple cycles for a long-term antineoplastic effect. In contrast, the pharmacokinetic profile of axi-cel leads to a slower initial decrease in tumor burden, but it is sustained after a single infusion due to potential persistence of CAR T cells in patients’ blood over time. Abbreviations: CAR, chimeric antigen receptor; LOD, limit of detection.