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.
10.3760/cma.j.issn.0253-2727.2023.10.003
- Author:
Ling Hui ZHOU
1
,
2
,
3
,
4
;
You Qin FENG
1
,
2
,
3
,
4
;
Yong Xian HU
1
,
2
,
3
,
4
;
He HUANG
1
,
2
,
3
,
4
Author Information
1. Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine
2. Liangzhu Laboratory, Zhejiang University Medical Center
3. Institute of Hematology, Zhejiang University
4. Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou 310003, China.
- Publication Type:Journal Article
- Keywords:
Chimeric antigen receptor T-cell;
Diffuse large B-cell lymphoma;
Prognosis;
ctDNA
- MeSH:
Humans;
Prognosis;
Receptors, Chimeric Antigen;
Circulating Tumor DNA/genetics*;
Feasibility Studies;
Lymphoma, Large B-Cell, Diffuse/therapy*;
Lymphoma, Non-Hodgkin;
Mutation;
Cell- and Tissue-Based Therapy;
Retrospective Studies;
Immediate-Early Proteins;
Tumor Suppressor Proteins
- From:
Chinese Journal of Hematology
2023;44(10):805-812
- CountryChina
- Language:Chinese
-
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.
