TY - JOUR
T1 - Development and Use of the Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy Axicabtagene Ciloleucel in Large B-Cell Lymphoma
T2 - A Review
AU - Locke, Frederick L.
AU - Go, William Y.
AU - Neelapu, Sattva S.
N1 - Funding Information:
personal fees and nonfinancial support from Kite/ Gilead and Novartis, and personal fees from Cellular BioMedicine Group during the conduct of the study; in addition, Dr Locke had a patent to Survivin vaccine pending. Dr Go reported receiving other from Kite, a Gilead Company, other from Gilead Biosciences during the conduct of the study, and other from A2 Biotherapeutics outside the submitted work. Dr Go was previously employed by Kite, a Gilead Company, is currently employed by A2 Biotherapeutics Inc, and has equity ownership in Gilead Sciences Inc and in A2 Biotherapeutics Inc. Dr Neelapu reported receiving grants, personal fees, and nonfinancial support from Kite, a Gilead Company, during the conduct of the study; personal fees from Novartis, grants and personal fees from Allogene, Celgene, Merck, and Unum Therapeutics; grants from BMS, Cellectis, Poseida, Karus, and Acerta; and personal fees from Pfizer, Precision Biosciences, Cell Medica, and Incyte outside the submitted work; in addition, Dr Neelapu had a patent to chimeric antigen receptor against CD79b pending. No other disclosures were reported.
Publisher Copyright:
© 2019 American Medical Association. All rights reserved.
PY - 2020/2
Y1 - 2020/2
N2 - Importance: Axicabtagene ciloleucel, an anti-CD19-CD28-CD3ζ 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.
AB - Importance: Axicabtagene ciloleucel, an anti-CD19-CD28-CD3ζ 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.
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U2 - 10.1001/jamaoncol.2019.3869
DO - 10.1001/jamaoncol.2019.3869
M3 - Review article
C2 - 31697310
AN - SCOPUS:85075037668
SN - 2374-2437
VL - 6
SP - 281
EP - 290
JO - JAMA Oncology
JF - JAMA Oncology
IS - 2
ER -