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).

Objective To explore the relationship among the changes of five coagulation indexes and clinical stage,metastasis in pre-operative patients with gastric carcinoma,and to investigate the coagulation in patients with different clinical stages and its clinical significance.Methods Eight hundred and sixty-eight gastric carcinoma patients( carcinoma group) who were firstly diagnosed and 213 patients ( control group) who were diagnosed as inguinal hernia in the same hospital during the same period were enrolled.Levels of rothrombin time (PT),activated partial thromboplastin rime (APTT),fibrinogen (FBG),plasma thrombin time (TT) and platelet count (PLT)were observed and compared in these two groups.Results (1)Compared with health control group,PT( [ 11.51 ± 1.21 ] s vs [ 11.27 ± 0.91 ] s,t =- 3.226,P ＜ 0.01 ),FBG( [ 3010.0 ±470.4] mg/L vs [ 2307.1 ± 651.8 ] mg/L,t =- 4.240,P ＜ 0.01 ) and PLT ( 238.57 ± 78.50 ) x 109/L vs (206.79 ±61.01 ) x 109/L,t =-5.514,P ＜0.01 )were significantly increased in gastric carcinoma group.(2)PT,FBG and PLT were significantly different between control group and different clinical stages of gastric carcinoma group ( P ＜ 0.05 or P ＜ 0.01 ).The levels of APTF,TT exhibited no significant difference between control group and different clinical stages of gastric carcinoma group ( P ＞ 0.05 ).( 3 ) Compared with gastric carcinoma without metastasis group,preoperative blood PT extended significantly ([ 11.41 ± 0.99] s vs [ 11.57 ± 1.32 ]s,t =- 2.095,P ＜ 0.05 ),FBG concentration increased significantly ( [ 2639.1 ± 748.6 ] mg/Lvs [ 3233.2 ± 591.60 ] mg/L,t =- 2.307,P ＜ 0.05 ) and PLT count increased significantly ( [ 224.02 ±76.94] x 109/L vs [ 247.32 ± 78.37 ] x 109/L,t =- 4.299,P ＜ 0.01 ) in gastric carcinoma with metastasis group.(4) Correlation analysis on four coagulation and PLT count with clinical stage:PT ( r =0.071,P ＜ 0.05 ),FBG ( r =0.271,P ＜ 0.01 ) and PLT( r =0.166,P ＜ 0.01 ) were positively correlated with clinical stage of gastric carcinoma and TT( r =- 0.077,P ＜ 0.05 ) was negatively correlated with clinical stage,among the total,the correlation coefficient of FBS with clinical stage was maximum.Conclusion Most patients with gastric cancer present state of blood coagulation and bleeding tendency,particularly in advanced gastric cancer,and with increased clinical stage of gastric cancer,some coagulation indicators showing a rising trend.Detection of coagulation index indirectly indicates the incidence,invasion and metastasis of gastric carcinoma.