CAR+ T-Cell Lymphoma after Cilta-cel Therapy for Relapsed or Refractory Myeloma
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 <i>TET2</i>-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.).
Authors
- Nitin Patel (ORCID: https://orcid.org/0009-0003-5084-5220)
- Yannick Le Bris (ORCID: https://orcid.org/0000-0002-0095-6999)
- Hannah G. Kelly (ORCID: https://orcid.org/0000-0002-4652-5609)
- Marion Eveillard (ORCID: https://orcid.org/0000-0001-7206-5135)
- Jane Oliaro (ORCID: https://orcid.org/0000-0002-2097-6428)
- Brad Foulk (ORCID: https://orcid.org/0000-0003-2502-2399)
- Ing Soo Tiong (ORCID: https://orcid.org/0000-0001-7417-4343)
- Juliette Eugene-Lamer
- Nikoletta K. Lendvai (ORCID: https://orcid.org/0000-0002-9849-4795)
- José Varela Donato Filho (ORCID: https://orcid.org/0009-0001-4010-9997)
- Vicki Plaks (ORCID: https://orcid.org/0000-0002-4809-9252)
- Stephen Lade (ORCID: https://orcid.org/0000-0002-6504-1343)
- Tamia Nguyen
- Patrice Chevallier (ORCID: https://orcid.org/0000-0003-3142-5581)
- Caroline Bodet‐Milin (ORCID: https://orcid.org/0000-0002-8219-3592)
- Marzia Rahman
- Sean M. Grimmond (ORCID: https://orcid.org/0000-0002-8102-7998)
- Denis A. Smirnov (ORCID: https://orcid.org/0000-0001-6864-5516)
- Katherine Li (ORCID: https://orcid.org/0000-0002-1578-5029)
- Erin Lee (ORCID: https://orcid.org/0000-0002-8728-7627)
- Arnob Banerjee (ORCID: https://orcid.org/0000-0002-4580-4657)
- Cyrille Touzeau (ORCID: https://orcid.org/0000-0003-0275-2575)
- Thomas Gastinne (ORCID: https://orcid.org/0000-0003-4704-1187)
- Loreta Marquez
- Nicole M. Haynes (ORCID: https://orcid.org/0000-0003-4991-6274)
- Carolina Lonardi
- Rebecca C Abbott (ORCID: https://orcid.org/0000-0002-0897-7874)
- Ana Slaughter
- Jeremy Er
- Benoît Tessoulin (ORCID: https://orcid.org/0000-0001-7600-3329)
- Éric Letouzé (ORCID: https://orcid.org/0000-0002-6369-2839)
- A. Sankari
- Jordan Mark Schecter (ORCID: https://orcid.org/0000-0001-5849-0987)
- William Deraedt (ORCID: https://orcid.org/0000-0003-1414-2387)
- Caroline Mayeur‐Rousse (ORCID: https://orcid.org/0000-0003-4070-3694)
- Martin Vogel
- Jessica Li (ORCID: https://orcid.org/0009-0007-2674-3194)
- Simon James Harrison (ORCID: https://orcid.org/0000-0003-4555-6582)
- Philippe Moreau (ORCID: https://orcid.org/0000-0003-1780-8746)
- Nicolas Kint (ORCID: https://orcid.org/0000-0003-0884-9298)
- Tamar Lengil
- Piers Blombery
- Hao Zhao
- Dong Geng
Institutions
- The Royal Melbourne Hospital (AU)
- Johnson & Johnson (United States) (US)
- Inserm (FR)
- The University of Melbourne (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Peter MacCallum Cancer Centre (AU)
- Ghent University Hospital (BE)
- Centre Hospitalier Universitaire de Nantes (FR)
- 490 BioTech (United States) (US)
- Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers (FR)
- Johnson & Johnson (Germany) (DE)
- Universitair Ziekenhuis Brussel (BE)
- Johnson & Johnson (United Kingdom) (GB)
- Institut National du Cancer (FR)
- Université d'Angers (FR)
- Nantes Université (FR)
Publication Details
- Journal
- New England Journal of Medicine
- Published
- 2025-02-12
- DOI
- https://doi.org/10.1056/nejmoa2309728
- Citations
- 41
- Primary Topic
- Lymphoma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 60.34