Analysis of the feasibility and prognostic value of circulating tumor DNA monitoring in detecting gene mutations in patients with diffuse large B-cell lymphoma receiving chimeric antigen receptor T-cell therapy / 中华血液学杂志
Chinese Journal of Hematology
; (12): 805-812, 2023.
Article
em Zh
| WPRIM
| ID: wpr-1012236
Biblioteca responsável:
WPRO
ABSTRACT
Objective:
To explore the prognostic value of circulating tumor DNA (ctDNA) testing in patients with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) undergoing chimeric antigen receptor T-cell (CAR-T) therapy, and to guide the prevention and subsequent treatment of CAR-T-cell therapy failure.Methods:
In this study, 48 patients with R/R DLBCL who received CAR-T-cell therapy at the First Affiliated Hospital of Zhejiang University School of Medicine between December 2017 and March 2022 were included. Furthermore, ctDNA testing of 187 lymphoma-related gene sets was performed on peripheral blood samples obtained before treatment. The patients were divided into complete remission and noncomplete remission groups. The chi-square test and t-test were used to compare group differences, and the Log-rank test was used to compare the differences in survival.Results:
Among the patients who did not achieve complete remission after CAR-T-cell therapy for R/R DLBCL, the top ten genes with the highest mutation frequencies were TP53 (41%), TTN (36%), BCR (27%), KMT2D (27%), IGLL5 (23%), KMT2C (23%), MYD88 (23%), BTG2 (18%), MUC16 (18%), and SGK1 (18%). Kaplan-Meier survival analysis revealed that patients with ctDNA mutation genes >10 had poorer overall survival (OS) rate (1-year OS rate 0 vs 73.8%, P<0.001) and progression-free survival (PFS) rate (1-year PFS rate 0 vs 51.8%, P=0.011) compared with patients with ctDNA mutation genes ≤10. Moreover, patients with MUC16 mutation positivity before treatment had better OS (2-year OS rate 56.8% vs 26.7%, P=0.046), whereas patients with BTG2 mutation positivity had poorer OS (1-year OS rate 0 vs 72.5%, P=0.005) .Conclusion:
ctDNA detection can serve as a tool for evaluating the efficacy of CAR-T-cell therapy in patients with R/R DLBCL. The pretreatment gene mutation burden, mutations in MUC16 and BTG2 have potential prognostic value.Palavras-chave
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Assunto principal:
Prognóstico
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Linfoma não Hodgkin
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Estudos de Viabilidade
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Estudos Retrospectivos
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Linfoma Difuso de Grandes Células B
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Proteínas Imediatamente Precoces
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Proteínas Supressoras de Tumor
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Terapia Baseada em Transplante de Células e Tecidos
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DNA Tumoral Circulante
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Receptores de Antígenos Quiméricos
Limite:
Humans
Idioma:
Zh
Revista:
Chinese Journal of Hematology
Ano de publicação:
2023
Tipo de documento:
Article