Abstract |
Chimeric antigen receptor-modified T (CAR T) cell therapy is a highly promising treatment for haematological malignancies but is frequently associated with cytokine release syndrome and neurotoxicity. Between July 2018 and July 2019, all patients treated with CD19-targeted CAR T-cell therapy for relapsing lymphoma were followed-up longitudinally to describe neurological symptoms and their evolution over time. Four different French centres participated and 84 patients (median age 59 years, 31% females) were included. Neurotoxicity, defined as the presence of at least one neurological symptom appearing after treatment infusion, was reported in 43% of the patients. The median time to onset was 7 days after infusion with a median duration of 6 days. More than half of the patients (64%) had grade 1-2 severity and 34% had grade 3-4. CRS was observed in 80% of all patients. The most frequent neurological symptoms were cognitive signs, being severe in 36%, and were equally distributed between language disorders and cognitive disorders without language impairment. Non-pyramidal motor disorders, severe in 11%, were reported in 42% of the patients. Elevation of C-reactive protein (CRP) within 4 days after treatment was significantly correlated with the occurrence of grade 3-4 neurotoxicity. Although sometimes severe, neurotoxicity was almost always reversible. The efficacy of steroids and antiepileptic drugs remains unproven in the management of neurotoxicity. Neurotoxicity associated with CAR T-cell therapies occurs in more than 40% of patients. The clinical pattern is heterogeneous but cognitive disorders (not limited to language disorders) and, to a minor degree, non-pyramidal motor disorders, appeared as a signature of severe neurotoxicity.
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Authors | Catherine Belin, Perrine Devic, Xavier Ayrignac, Amélie Dos Santos, Adrien Paix, Lila Sirven-Villaros, Claire Simard, Sylvain Lamure, Thomas Gastinne, Renata Ursu, Colette Berger, Laura Platon, Benoît Tessoulin, Elie Azoulay, Florent Wallet, Catherine Thieblemont, Emmanuel Bachy, Guillaume Cartron, David A Laplaud, Antoine F Carpentier |
Journal | Scientific reports
(Sci Rep)
Vol. 10
Issue 1
Pg. 18997
(11 04 2020)
ISSN: 2045-2322 [Electronic] England |
PMID | 33149178
(Publication Type: Journal Article, Multicenter Study)
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Chemical References |
- CD19-specific chimeric antigen receptor
- Receptors, Antigen, T-Cell
- C-Reactive Protein
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Topics |
- Adult
- Aged
- C-Reactive Protein
(metabolism)
- Female
- Humans
- Immunotherapy, Adoptive
(adverse effects)
- Lymphoma, B-Cell
(metabolism, therapy)
- Male
- Middle Aged
- Neurotoxicity Syndromes
(epidemiology, metabolism)
- Prospective Studies
- Receptors, Antigen, T-Cell
(metabolism)
- Severity of Illness Index
- Survival Analysis
- Treatment Outcome
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