Objective:To evaluate the long-term efficacy and safety of B cell maturation antigen(BCMA)-chimeric antigen receptor-T(CAR-T)cells in the treatment of recurrent/refractory multiple myeloma(R/R MM).Methods:A retrospective analysis was conducted on the clinical data of 20 patients with R/R MM who received BCMA CAR-T-cell therapy at The First Affiliated Hospital of Nanchang University between July 2018 and July 2023.The follow-up period was up to December 31,2023.Overall survival and progression-free survival(PFS)rates were eval-uated using Kaplan-Meier analysis,and adverse effects were recorded.Results:Of all 20 cases with R/R MM,the median number of previ-ous treatment lines was three(range:two to six),total objective response rate(ORR)was 75%,and complete response(CR)rate was 50%.The median follow-up duration was 29 months,with a median PFS of 26 months.Among ten patients with CR,five were still in remission at the last follow-up,with the shortest duration of remission being 6 months and the longest being 48 months.In the subgroup analysis,PFS was significantly worse in patients with extramedullary infiltration,high tumor burden,and 17p deletion high-risk cytogenetic features(P<0.05).Cytokine release syndrome(CRS)was the most common(90%)adverse event,and it was mostly mild,with an incidence rate of grade 3 or higher of 35%.Few long-term adverse effects occurred and no CAR-T cell treatment-related deaths were observed.Conclusions:BCMA CAR-T-cell therapy was effective and safe for patients with R/R MM.Patients with extramedullary diseases and high tumor burden can also benefit from this treatment;however,their persistent response is not satisfactory.It is worth exploring the differences and design-ing prospective clinical studies to consolidate and maintain the efficacy in these patients.

Summary: The inhibitory effects ofparthenolide (PTL) on angiogenesis induced by multiple myeloma (MM) cells in vitro, and the mechanism were investigated. Human MM line RPMI8226 cells were cultured in vitro. The effects of MM culture supernatant on the migration and tubule formation ability of human umbilical vein endothelial cells (HUVECs) treated with PTL were observed. By using Western blot, the expression of p65 and IκB-α in MM cells was detected. RT-PCR was used to assay the expression of VEGF, IL-6, MMP2 and MMP9 mRNA in MM cells. ELISA was used to measure the levels of VEGF and IL-6 in MM cell culture supernatant. The expression of MMP2 and MMP9 in MM cells was examined by immunohistochemistry. (1) In 3.5, 5.0, 7.5 and 10 μmol/L PTL groups the number of migrated cells was 310±56, 207±28, 127±21 and 49±10 respectively, which was significantly different from that in positive control group (598±47) (P<0.01). In 3.5 and 5.0 μmol/L PTL groups the areas of capillary-like structures were 0.092±0.003 and 0.063±0.002 mm2, significantly less than in positive control group (0.262±0.012 mm2) (P<0.01), but in 7.5 and 10 μmol/L PTL groups no capillary-like structures were found;(2) After treatment with different concentrations of PTL for 48 h, the expression of p65 protein was gradually decreased, while that of IκB-α was gradually enhanced with the increased concentration of PTL;(3) After treatment with 3.5,5.0, 7.5 and 10 μmol/L PTL for 48 h, the VEGF levels in the supematant were 2373.4±392.2,1982.3±293.3, 1247.0±338.4 and 936.5±168.5 pg/mL respectively, significantly different from those in positive control group (2729±440.0 pg/mL) (P<0.05). After treatment with 7.5 and 10 μmol/L PTL, the IL-6 levels in the culture supernatant were 59.6±2.8 and 41.4±9.8 pg/mL respectively, significantly lower than in positive control group (1287.3±43.5 pg/mL) (P<0.05);(4) RT-PCR revealed that PTL could significantly inhibit the expression of VEGF and IL-6 mRNA in MM cells, but not influence the expression of MMP2 and MMP9 mRNA.;(5) Immunohisto chemistry indicated that PTL had no significant effects on the expression of MMP2 and MMP9 protein in MM cells. It was concluded that the abilities of the culture supematant of MM cells treated with PTL to induce endothelial cells migration and tubule formation were significantly reduced, suggesting PTL could obviously inhibit the angiogenesis induced by MM cells. PTL could decrease NF-kappaB activity and significantly suppress the expression of VEGF and IL-6 mRNA and protein, which might contribute to the mechanism by which PTL inhibited the angiogenesis induced by MM cells.