Myeloid neoplasms after CD19-directed CAR T cells therapy in long-term B-cell lymphoma responders, a rising risk over time?
Therapy-related myeloid neoplasms (t-MN), including myelodysplastic neoplasms (t-MDS) and acute myeloid leukemia (t-AML), have emerged as significant late complications after CAR T cell therapy. We retrospectively analyzed 539 patients with B cell lymphoma treated with CD19 directed CAR T cell therapy across four French centers. Cumulative incidences of t-MN was estimated with relapse or death treated as competing risk. Univariate and propensity score matching (PSM) analyses were conducted to assess risk factors with age and the number of prior treatments as covariates. After a median follow-up of 25 months, the cumulative incidence of t-MN was 4.5% at 2 years. T-MN occurred predominantly as t-MDS (62%) and t-AML (38%) with high cytogenetic risk. Median overall survival after t-MN diagnosis was 4.5 months. In univariate analysis, older age (p < 0.01), higher MCV (p < 0.01), and higher ICANS grade (p = 0.04) were associated with increased risk of t-MN. After PSM, MCV and ICANS grade remained significant risk factors. CAR T cell products with CD28 co-stimulatory domains trended towards higher t-MN risk (p = 0.09). NGS analysis showed that 85.7% of t-MN had pre-existing mutations, most commonly TP53. This study highlights t-MN as a severe late complication of CAR T cell therapy. MCV and ICANS grade were identified as key risk factors.
Authors
- Maël Heiblig (ORCID: https://orcid.org/0000-0003-1682-8657)
- Nicolas Gower
- Benjamin Podvin (ORCID: https://orcid.org/0000-0002-0616-8694)
- Nicolas Gazeau (ORCID: https://orcid.org/0000-0003-3449-6676)
- Paul Chauvet (ORCID: https://orcid.org/0000-0001-6326-9283)
- Rémi Tilmont (ORCID: https://orcid.org/0000-0003-1739-2162)
- Julie Demaret (ORCID: https://orcid.org/0000-0001-6960-4521)
- David Beauvais (ORCID: https://orcid.org/0000-0003-1866-828X)
- Micha Srour (ORCID: https://orcid.org/0000-0002-8519-4187)
- Franck Morschhauser
- Ibrahim Yakoub‐Agha (ORCID: https://orcid.org/0000-0003-4524-8782)
- Emmanuel Bachy (ORCID: https://orcid.org/0000-0003-2694-7510)
- Gandhi Laurent Damaj (ORCID: https://orcid.org/0000-0002-4689-3882)
- Pierre Sesques (ORCID: https://orcid.org/0000-0001-8264-822X)
- Violaine Safar
- Nicolas Duployez (ORCID: https://orcid.org/0000-0002-3927-1022)
- Sarah Huet (ORCID: https://orcid.org/0000-0002-3408-2783)
- Pierre Sujobert (ORCID: https://orcid.org/0000-0003-1724-4792)
- Pascale Flandrin‐Gresta (ORCID: https://orcid.org/0000-0001-6258-7028)
- Emmanuelle Ferrant
- Hervé Ghesquières
- Ludovic Fouillet
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université de Lille (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Hospices Civils de Lyon (FR)
- Hôpital Lyon Sud (FR)
- Centre Hospitalier Universitaire de Caen Normandie (FR)
- Hôpital Nord (FR)
- Lille Inflammation Research International Center (FR)
- Centre Hospitalier Universitaire de Saint-Étienne (FR)
- Protéomique, Réponse Inflammatoire et Spectrométrie de Masse (FR)
- Institute for Translational Research in Inflammation (FR)
Publication Details
- Journal
- Leukemia
- Published
- 2025-04-24
- DOI
- https://doi.org/10.1038/s41375-025-02605-7
- Citations
- 12
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 12.54
Funders
- Hospices Civils de Lyon