Efficacy and safety of a novel CD19, CD22 dual-targeted fully human loop bi-CAR-T for the treatment of relapsed/refractory B cell non-Hodgkin lymphoma

Background Chimeric antigen receptor (CAR) T-cell therapies targeting CD19 have demonstrated promising efficacy in treating refractory or relapsed B-cell malignancies. Nonetheless, challenges such as antigen escape-mediated relapse and toxicities, including cytokine release syndrome (CRS) and neurot...

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Vydáno v:Journal of translational medicine Ročník 23; číslo 1; s. 630 - 13
Hlavní autoři: Wang, Hanyu, Wang, Gaoxiang, Li, Tongjuan, Zhang, Peiling, Mao, Zekai, Luo, Hui, Zhu, Xiaojian, Li, Dengju, Zhou, Jianfeng, Zhou, Xiaoxi, Huang, Liang
Médium: Journal Article
Jazyk:angličtina
Vydáno: London BioMed Central 05.06.2025
BioMed Central Ltd
BMC
Témata:
Adult
Aged
Antigens, CD19 - immunology
Antigens, CD19 - metabolism
Biomedical and Life Sciences
Biomedicine
Cell
Drug therapy
Female
Humans
Immunotherapy, Adoptive - adverse effects
Lymphoma, B-Cell - immunology
Lymphoma, B-Cell - therapy
Lymphoma, Non-Hodgkin - therapy
Male
Medicine/Public Health
Middle Aged
Neoplasm Recurrence, Local
Non-Hodgkin's lymphomas
Patient outcomes
Physiological aspects
Receptors, Chimeric Antigen - metabolism
Recurrence
Sialic Acid Binding Ig-like Lectin 2 - immunology
Sialic Acid Binding Ig-like Lectin 2 - metabolism
tissue and gene therapy
Treatment Outcome
China
ISSN:1479-5876, 1479-5876
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Shrnutí:Background Chimeric antigen receptor (CAR) T-cell therapies targeting CD19 have demonstrated promising efficacy in treating refractory or relapsed B-cell malignancies. Nonetheless, challenges such as antigen escape-mediated relapse and toxicities, including cytokine release syndrome (CRS) and neurotoxicity, may impede their clinical application. Methods In this study, we developed a fully human, bivalent loop bi-CAR-T targeting both CD19 and CD22 (CT120). We conducted an open-label, single-center, single-arm phase I/II trial to evaluate the efficacy and safety of CT120 in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). Results The overall response rate (ORR) was 65.2%, with 56.5% of patients achieving a complete response. The median progression-free survival (PFS) was 23.95 months, and the median overall survival (OS) was not reached. The 12-month PFS rate was 54.66%, and the 12-month OS rate was 77.34%. The 24-month PFS rate was 49.69% and the 24-month OS rate was 72.51%. Prognostic factors for poorer outcomes included bulky mass, high international prognostic index (IPI), multiple extranodal lesions, or MYD88 mutation. No loss of CD19/CD22 expression was observed in patients with relapse. Grade 3 or higher CRS occurred in only one patient (4.3%), and no immune effector cell-associated neurotoxicity syndrome (ICANS) was seen. Notably, we observed both early and late immune effector cell-associated hematotoxicity (ICAHT) following CT120 infusion. Late-onset neutropenia (after day 30) occurred in 78.3% of patients, and severe anemia was correlated with worse prognosis. Conclusions Overall, CT120 infusion is effective, safe, and reliable for reducing antigen escape-related relapse in patients with relapsed or refractory NHL. Trial registration Chinese Clinical Trial Registry (ChiCTR), ChiCTR2000038641). Registered 26 September 2020, https://www.chictr.org.cn/showproj.html?proj=61780 .
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1479-5876
1479-5876
DOI:10.1186/s12967-025-06567-3