
Activity ID
13730Expires
December 12, 2027Format Type
Journal-basedCME Credit
1Fee
$30CME Provider: JAMA Oncology
Description of CME Course
Importance The commercialization of chimeric antigen receptor–T-cell (CAR-T) therapy has changed the landscape of treatment of hematological cancers. Numerous studies from the early 2000s paved the way for cell-based targeted therapeutics, which have been established as practice-changing therapies in lymphoma, leukemia, and multiple myeloma. However, there has been some recent concern about the risk for second primary cancers (SPCs).
Observations Multiple cases of SPCs arising after CAR-T therapy have been reported to the US Food and Drug Administration. Most SPCs have been negative for the chimeric antigen receptor transgene, with rare reports of transgene-positive cancers. This review summarizes the most salient literature on epidemiology and pathobiology of SPCs after CAR-T therapy. Additionally, a discussion is provided on potential mitigation strategies for SPCs after CAR-T therapies.
Conclusions and Relevance The results of this review suggest that there are limited data to suggest that inadvertent transgene insertion is associated with SPCs in the post–CAR-T setting. Nonetheless, evidence-based practical solutions and scientific strategies for risk mitigation can be implemented. These include optimization of T-cell manufacturing, application of safer synthetic immunobiology, and implementation of high-fidelity genomic testing, including baseline screening for clonal hematopoiesis. These strategies may inform optimal design of the next generation of CAR-T products that confer minimal risk for SPCs such that the risk-benefit profile remains favorable to proceed with CAR-T administration for eligible patients.
Disclaimers
1. This activity is accredited by the American Medical Association.
2. This activity is free to AMA members.
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ABMS Lifelong Learning CME Activity
Allergy and Immunology
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Commercial Support?
NoNOTE: If a Member Board has not deemed this activity for MOC approval as an accredited CME activity, this activity may count toward an ABMS Member Board’s general CME requirement. Please refer directly to your Member Board’s MOC Part II Lifelong Learning and Self-Assessment Program Requirements.
Educational Objectives
To identify the key insights or developments described in this article
Keywords
Targeted and Immune Therapy, Cancer Screening, Prevention, Control, Hematologic Cancer, Hematology, Oncology
Competencies
Medical Knowledge
CME Credit Type
AMA PRA Category 1 Credit
DOI
10.1001/jamaoncol.2024.5412