A distinct cytokine network distinguishes chimeric antigen receptor T cell (CAR-T)-associated hemophagocytic lymphohistiocytosis-like toxicity (carHLH) from severe cytokine release syndrome following CAR-T therapy.
Cytotherapy
; 25(11): 1167-1175, 2023 11.
Article
em En
| MEDLINE
| ID: mdl-37480884
ABSTRACT
BACKGROUND AIMS:
With the increasing application of chimeric antigen receptor (CAR)-T cell therapy in various malignancies, an extra toxicity profile has been revealed, including a severe complication resembling hemophagocytic lymphohistiocytosis (HLH), which is usually disguised by severe cytokine release syndrome (CRS).METHODS:
In a clinical trial in whom 99 patients received B-cell maturation antigen CAR-T cells, we identified 20 (20.20%) cases of CAR-T cell-associated HLH (carHLH), most of whom possessed a background of severe CRS (grade ≥3). The overlapping features of carHLH and severe CRS attracted us to further explore the differences between them.RESULTS:
We showed that carHLH can be distinguished by extreme elevation of interferon-γ, granzyme B, interleukin-1RA and interleukin-10, which can be informative in developing prevention and management strategies of this toxicity. Moreover, we developed a predictive model of carHLH with a mean area under the curve of 0.81 ± 0.07, incorporating serum lactate dehydrogenase at day 6 post-CRS and serum fibrinogen at day 3 post-CRS.CONCLUSIONS:
The incidence of carHLH in CAR-T recipients might be relatively higher than we previously thought. relatively higher than we previously. A cytokine network distinguished from CRS is responsible for carHLH. And corresponding cytokine-directed therapies, especially targeting IL-10, are worth trying.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfo-Histiocitose Hemofagocítica
/
Receptores de Antígenos Quiméricos
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cytotherapy
Assunto da revista:
TERAPEUTICA
Ano de publicação:
2023
Tipo de documento:
Article