CAR+ T-Cell Lymphoma after Cilta-cel Therapy for Relapsed or Refractory Myeloma

Harrison, SJ; Touzeau, C; Kint, N; Li, K; Nguyen, T; Mayeur-Rousse, C; Rahman, M; Le Bris, Y; Er, J; Eugene-Lamer, J; Haynes, NM; Li, J; Abbott, RC; Bodet-Milin, C; Moreau, A; Letouz&#233;, E; Lendvai, N; Schecter, JM; Deraedt, W; Banerjee, A; Lengil, T; Vogel, M; Foulk, B; Zhao, H; Smirnov, D; Slaughter, A; Lonardi, C; Lee, E; Marquez, L; Sankari, A; Plaks, V; Filho, JOC; Patel, N; Geng, D; Gastinne, T; Kelly, H; Tiong, IS; Eveillard, M; Chevallier, P; Lade, S; Moreau, P; Grimmond, S; Oliaro, J; Tessoulin, B; Blombery, P

Author(s): Harrison, SJ; Touzeau, C; Kint, N; Li, K; Nguyen, T; Mayeur-Rousse, C; Rahman, M; Le Bris, Y; Er, J; Eugene-Lamer, J; Haynes, NM; Li, J; Abbott, RC; Bodet-Milin, C; Moreau, A; Letouzé, E; Lendvai, N; Schecter, JM; Deraedt, W; Banerjee, A; Lengil, T; Vogel, M; Foulk, B; Zhao, H; Smirnov, D; Slaughter, A; Lonardi, C; Lee, E; Marquez, L; Sankari, A; Plaks, V; Filho, JOC; Patel, N; Geng, D; Gastinne, T; Kelly, H; Tiong, IS; Eveillard, M; Chevallier, P; Lade, S; Moreau, P; Grimmond, S; Oliaro, J; Tessoulin, B; Blombery, P;
Details: Publication Year 2025-02-13,Volume 392,Issue #7,Page 677-685
Journal Title: New England Journal of Medicine
Publication Type: Case report
Abstract: We describe two patients in whom malignant monoclonal T-cell lymphoproliferation developed after administration of chimeric antigen receptor (CAR) T-cell therapy with ciltacabtagene autoleucel (cilta-cel) in the phase 3 CARTITUDE-4 trial. Monoclonal T cells from both patients had detectable CAR transgene expression and integration. The clinicogenomic features of these CAR transgenic T-cell lymphoproliferative neoplasms suggest that multiple potential intrinsic or extrinsic factors (or both) contributed to their pathogenesis, such as transduction of preexisting TET2-mutated T cells, followed by acquisition of further oncogenic genomic variants. Other potential contributors include germline genomic variation, viral infections, and previous treatment for myeloma. In the absence of direct evidence, the contribution of insertional mutagenesis to the development of T-cell lymphoma is currently unclear. (Funded by Johnson & Johnson and Legend Biotech USA; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.).
Keywords: Humans; *Immunotherapy, Adoptive/adverse effects; *Receptors, Chimeric Antigen/therapeutic use; *Multiple Myeloma/therapy/genetics; Male; Middle Aged; Lymphoma, T-Cell/therapy; Female; Aged; Receptors, Antigen, T-Cell/genetics/therapeutic use; Recurrence; Antigens, CD19/therapeutic use; T-Lymphocytes/immunology; Biological Products
Department(s): Haematology; Pathology; Laboratory Research; Parkville Cancer Clinical Trials Unit
Publisher's Version: https://doi.org/10.1056/NEJMoa2309728
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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