The New England Journal of MedicineRisk of Second Tumors and T-Cell Lymphoma after CAR T-Cell Therapy

Second Tumors After CAR T-Cell Therapy: Molecular Insights and Clinical Implications

Chimeric antigen receptor (CAR) T-cell therapy, a breakthrough in cancer treatment, has raised concerns about the risk of second tumors, particularly T-cell lymphomas. This study reviews clinical experiences with CAR T-cell therapy to ascertain the occurrence and characteristics of second tumors, with a focus on molecular and genetic profiling.

Study Design:

• Reviewed clinical experience with adoptive cellular CAR T-cell therapy since 2016.
• Included 724 patients treated with T-cell therapies at a single institution.
• Detailed molecular, genetic, and cellular analysis conducted on cases of second tumors.

Key Findings:

• One patient developed a lethal T-cell lymphoma after receiving axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma.
• Both the initial and secondary lymphomas exhibited distinct molecular immunophenotypes and genomic profiles.
• Epstein-Barr virus (EBV) was detected in both lymphomas, linked with DNMT3A and TET2 mutant clonal hematopoiesis.
• No evidence of oncogenic retroviral integration was found in the tumor analysis.
• The study demonstrates the rarity of second tumors following CAR T-cell therapy.

HCN Medical Memo
This study highlights the importance of monitoring for second tumors in patients undergoing CAR T-cell therapy. Physicians should be aware of the molecular characteristics and potential viral associations of secondary malignancies to better manage and counsel their patients.

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