A clonally expanded nodal T-cell population diagnosed as T-cell lymphoma after CAR-T therapy
Reports of secondary malignancies after chimeric antigen receptor (CAR)-T and possible CAR-T derived malignant transformation necessitate caution. Here we describe a patient with diffuse large B-cell lymphoma who developed new lymphadenopathy 2.5 years after CAR-T in the context of COVID-19 infection with histopathologic features consistent with T-cell lymphoma (TCL). Deep molecular interrogation with genomic sequencing and single-cell spatial transcriptomics reveals a highly proliferative clonal T-cell population co-expressing CD4 and CD8 with biallelic TCR rearrangement and no evidence of the CAR construct. The expanded clonotype displayed T follicular helper (TFH) cell transcriptomic programs and occupies immune-excluded spatial niches within the lymph node, supportive of TFH-like neoplastic T cell behavior. Remarkably, the lymphadenopathy spontaneously resolved on interval imaging. Our data underscore the need for better understanding of post-CAR-T clonal T-cell lymphoproliferative disorders to avoid unnecessary treatment and higher specificity in diagnostic methods for TCL.
Authors
- Gad A. Getz (ORCID: https://orcid.org/0000-0002-0936-0753)
- Jackson A. Weir (ORCID: https://orcid.org/0000-0001-8741-1344)
- Phillip D. Michaels (ORCID: https://orcid.org/0000-0003-3827-953X)
- Laura E. Moreno Luna
- Emma Lin
- Jacob Shapiro
- Hariharan Bharadwaj (ORCID: https://orcid.org/0000-0003-4550-4811)
- Vipin Kumar (ORCID: https://orcid.org/0000-0003-0910-233X)
- Caron Alyce Jacobson (ORCID: https://orcid.org/0000-0002-0180-0654)
- Adi Nagler (ORCID: https://orcid.org/0000-0003-2127-5938)
- Linsey Gong
- Brianna Waller
- Catherine J. Wu (ORCID: https://orcid.org/0000-0002-3348-5054)
- Jacob P. Laubach (ORCID: https://orcid.org/0000-0001-7565-2052)
- Katie Maurer (ORCID: https://orcid.org/0000-0002-4160-181X)
- Nicholas J. Haradhvala (ORCID: https://orcid.org/0000-0003-1113-3135)
- Jorge Cruz (ORCID: https://orcid.org/0000-0001-5361-0927)
- Fei Chen (ORCID: https://orcid.org/0000-0003-2308-3649)
- Mehdi Borji (ORCID: https://orcid.org/0009-0002-7023-434X)
- Qiyu Gong
- Geraldine Pinkus
- Mikaela M. McDonough
- Somkene Alakwe
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Dana-Farber Cancer Institute (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-12
- DOI
- https://doi.org/10.1038/s41467-025-62709-7
- Citations
- 1
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 1.05
Funders
- New York Stem Cell Foundation
- Dana-Farber Cancer Institute
- Parker Institute for Cancer Immunotherapy
- National Cancer Institute