Locke FL, et al. - Researchers here focus on axicabtagene ciloleucel, an anti-CD19-CD28-CD3ζ chimeric antigen receptor T-cell therapy, the first US Food and Drug Administration–approved, genetically engineered T-cell therapy for adults with relapsed or refractory large B-cell lymphoma (LBCL) after 2 or more lines of systemic therapy. In patients with refractory LBCL, efficacy of axicabtagene ciloleucel has been demonstrated. In this review, they delineate a timeline of the rapid clinical development of axicabtagene ciloleucel from bench to bedside, describe how axicabtagene ciloleucel satisfies an unmet medical need for treatment of refractory LBCL, explain the logistics of the production process and administration of axicabtagene ciloleucel, describes its mechanism of action, and compiles the results of the pivotal study. Further, in this review, a survey of adverse events was delineated, with attention to the kinetics of their clinical presentation; the management of adverse events was addressed; and suggestions for appropriate patient selection for safe administration of axicabtagene ciloleucel were offered. In the treatment of patients with LBCL, the integration of axicabtagene ciloleucel therapy into standard-of-care practice for relapsed/refractory LBCL represents the commencement of a paradigm shift and may result in improvements in their survival and curability. For optimal patient outcomes, they emphasize timely referral to centers offering the therapy.