Axicabtagene Ciloleucel (Yescarta®): A Comprehensive Clinical and Scientific Review

I. Executive Summary

Axicabtagene ciloleucel, marketed under the brand name Yescarta®, is a CD19-directed, genetically modified autologous T-cell immunotherapy that represents a paradigm shift in the treatment of certain B-cell malignancies.[1] As a living drug, it is manufactured on a patient-specific basis by harvesting a patient's T-cells, engineering them

ex vivo to express a chimeric antigen receptor (CAR) that targets the CD19 protein on lymphoma cells, and infusing them back into the patient to elicit a potent anti-tumor immune response.[2] This report provides a comprehensive analysis of its foundational science, clinical evidence, regulatory history, and therapeutic context.

The clinical development of axicabtagene ciloleucel has been marked by landmark trials demonstrating profound and durable efficacy. The pivotal ZUMA-1 trial established its value in the third-line or later setting for relapsed or refractory (R/R) large B-cell lymphoma (LBCL), showing a 5-year overall survival rate of 42.6% in a patient population with a historically dismal prognosis, suggesting curative potential for a significant subset of patients.[4] More significantly, the randomized Phase 3 ZUMA-7 trial demonstrated the superiority of axicabtagene ciloleucel over the long-standing standard of care (SOC)—salvage chemotherapy followed by high-dose therapy and autologous stem cell transplant—in the second-line treatment of high-risk LBCL.[1] This trial led to a fundamental reordering of the treatment algorithm, establishing CAR-T therapy as a new standard in an earlier line of treatment for patients with primary refractory disease or early relapse.[7]