• N. Engl. J. Med. · Feb 2025

    Case Reports

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

    • Simon J Harrison, Cyrille Touzeau, Nicolas Kint, Katherine Li, Tamia Nguyen, Caroline Mayeur-Rousse, Marzia Rahman, Yannick Le Bris, Jeremy Er, Juliette Eugene-Lamer, Nicole M Haynes, Jessica Li, Rebecca C Abbott, Caroline Bodet-Milin, Anne Moreau, Eric Letouzé, Nikoletta Lendvai, Jordan M Schecter, William Deraedt, Arnob Banerjee, Tamar Lengil, Martin Vogel, Brad Foulk, Hao Zhao, Denis Smirnov, Ana Slaughter, Carolina Lonardi, Erin Lee, Loreta Marquez, Ayah Sankari, Vicki Plaks, Jose Octavio Costa Filho, Nitin Patel, Dong Geng, Thomas Gastinne, Hannah Kelly, Ing Soo Tiong, Marion Eveillard, Patrice Chevallier, Stephen Lade, Philippe Moreau, Sean Grimmond, Jane Oliaro, Benoit Tessoulin, and Piers Blombery.
    • Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
    • N. Engl. J. Med. 2025 Feb 13; 392 (7): 677685677-685.

    AbstractWe 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.).Copyright © 2025 Massachusetts Medical Society.

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