Development and Use of the Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy Axicabtagene Ciloleucel in Large B-Cell Lymphoma: A Review
Cette étude passe en revue les différentes étapes de développement de l'axicabtagène ciloleucel (un médicament à base de lymphocytes CAR-T ciblant CD19, CD28 et CD3zêta) pour le traitement des lymphomes à grandes cellules B, décrit son mécanisme d'action, résume les résultats de l'étude pivot, identifie les effets secondaires et analyse leur prise en charge
Importance : Axicabtagene ciloleucel, an anti-CD19-CD28-CD3zêta
chimeric antigen receptor T-cell therapy, was 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. There has not been a US Food and Drug Administration–approved product for these cancers in more than 4 decades. Observations : Unlike traditional anticancer therapies, axicabtagene ciloleucel is a patient-specific, live-cell product that has unique requirements for manufacturing, shipping, and storage, as well as for its administration and management of its adverse events. In addition, axicabtagene ciloleucel has demonstrated efficacy in patients with refractory LBCL. This review presents a timeline of the rapid clinical development of axicabtagene ciloleucel from bench to bedside, highlights how axicabtagene ciloleucel satisfies an unmet medical need for treatment of refractory LBCL, outlines the logistics of the production process and administration of axicabtagene ciloleucel, describes its mechanism of action, and summarizes the results of the pivotal study. This review also provides a survey of adverse events, with attention to the kinetics of their clinical presentation; discusses the management of adverse events; and offers suggestions for appropriate patient selection for safe administration of axicabtagene ciloleucel. Conclusions and Relevance : The integration of axicabtagene ciloleucel therapy into standard-of-care practice for relapsed/refractory LBCL is the beginning of a paradigm shift in the treatment of patients with LBCL and is likely to lead to improvements in their survival and curability. Timely referral to centers offering the therapy is necessary for optimal patient outcomes.