Predictive value of pre-treatment circulating tumor DNA genomic landscape in patients with relapsed/refractory multiple myeloma undergoing anti-BCMA CAR-T therapy: Insights from tumor cells and T cells.
10.1097/CM9.0000000000003306
- Author:
Rongrong CHEN
1
;
Chunxiang JIN
2
;
Kai LIU
3
;
Mengyu ZHAO
1
;
Tingting YANG
1
;
Mingming ZHANG
1
;
Pingnan XIAO
1
;
Jingjing FENG
1
;
Ruimin HONG
1
;
Shan FU
1
;
Jiazhen CUI
3
;
Simao HUANG
3
;
Guoqing WEI
1
;
He HUANG
1
;
Yongxian HU
1
Author Information
1. Bone Marrow Transplantation Center of The First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.
2. School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, China.
3. Hematology and Immunology Laboratory, Liangzhu Laboratory, School of Medicine, Zhejiang University , Hangzhou, Zhejiang 310000, China.
- Publication Type:Journal Article
- From:
Chinese Medical Journal
2024;138(19):2481-2490
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.
METHODS:Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.
RESULTS:In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P = 0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P = 0.037), and higher percentages of CD8+ T cells (P = 0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) (P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [P = 0.004], IRF4 [P = 0.024], and CREBBP [P = 0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P = 0.040) were independent risk factors for PFS.
CONCLUSION:Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.
REGISTERATION:Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).
