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 evaluate the efficacy difference of different embolization agents in transcatheter embolization for treating massive hemoptysis caused by systemic pulmonary circulation shunt(SPS). Methods The clinical and imaging data in 98 patients with hemoptysis complicating SPS,including bronchodilator in 72 cases,pulmonary tuberculosis in 18 cases and lung carcinoma in 8 cases. All cases were treated with bronchial arterial embolization (BAE). According to different used embolization agents, the cases were divided into the gelfoam group and polyvinyl alcohol(PVA)grains embolization group. All cases were followed up at postoperative 1 d,1,3,6 months as well as 1,2 years. The data were analyzed by using Ridit test. Results Ninety-eight cases of massive hemoptysis were confirmed by DSA,among them,84 cases were complicating pulmonary artery fistula, 18 cases were pulmonary venous fistula and 2 cases were mixed fistula; 32 cases were simple BPS, 62 cases were pulmonary circulation fistula existed in the bronchial arteries and non-bronchial artery and 4 cases were simple non-BPS. The two groups had no complications such as embolism,paraplegia,esophagus-trachea fistula and skin ischemic necrosis. The follow up on postoperative 1 d, at postoperative 1, 3,6 months and at postoperative 1,2 years indicated that among 48 cases in the gelfoam group, 20 cases were cured, 18 cases were significantly effective,6 cases were effective and 4 cases were ineffective,the effective rate was 91.7 % ;among 50 cases in the PVA grain embolization group, 38 cases were cured, 8 cases were significantly effective,4 cases were effective and O case was ineffective, the effective rate was 100%. Moreove no severe complications such as ectopic embolism, paraplegia, esophagus-trachea fistula and skin ischemic necrosis occurred. The difference between the two groups had statistical significance by Ridit analysis. Conclusion Transcatheter embolization for treating massive hemoptysis caused by SPS is safe and reliable,has small trauma, using PVA grains embolization can reduce the long term recurrence rate of hemoptysis.