| Part Ⅰ Retrospective analysis of clinical data on efficacy and safety ofhuman-derived BCMA CAR-T in the treatment of relapsed andrefractory multiple myeloma Objectives:To Study the efficacy and safety of human-derived chimeric antigen receptor Tcells(CAR-T)targeted B Cell Maturation Antigen(BCMA)in the treatment of relapsed and refractory multiple myeloma,while monitoring the duration of BCMA CAR-T cells in patients.Methods:Nine RRMM patients with complete clinical data who received human-targeted BCMA CAR-T therapy from July 2019 to October 2022 were analyzed.Before reinfusion of BCMA CAR-T cells,pretreatment with cyclophosphamide combined with fludarabine(FC)regimen was performed,and the patient’s vital signs(blood pressure,heart rate,body temperature,blood oxygen saturation)were monitored.Dynamically monitor changes in blood routine,liver and kidney function,electrolytes,inflammatory factors,procalcitonin,hematuria fixed electrophoresis,bone marrow residual assessment,CAR-T copy number and other indicators according to time points,and follow up until the patient’s disease recurrence(Progressive disease,PD),death or lost to follow-up.The curative effect was evaluated according to the 2020 edition of Chinese guidelines for the diagnosis and treatment of multiple myeloma.Cytokine Release Syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome were evaluated according to the American Society For Transplantation and Cellular Therapy to assess security.Results:1.Efficacy: Among the 9 patients treated with human-derived BCMA-targeted CAR-T cells for RRMM,9 cases were evaluated for efficacy,the ORR was 89%,and the three-month ORR was 89%.Follow-up until February 2023,2 cases of CR,1 case of VGPR,2 cases of PR,1 case of SD,and 3 cases of PD.4 cases of EMM,as of February 2023,1 case of PR,1 case of VGPR,and 2 cases of PD.2.Safety: The incidence rate of CRS was 89%(8/9),the incidence rate of grade2 CRS was 77.8%(7/9),and the incidence rate of grade 3 CRS was 11.1%(1 /9),none of these 9 patients had ICANS.3.CAR T cell survivability: After reinfusion of CAR-T cells,the presence of CAR-T cells could be detected in the peripheral blood of all patients,and the median value of the peak period of CAR-T expansion was 8.5 days(7-22 days),and all of them were within 28 days after the reinfusion of CAR-T cells reached a peak level and then gradually decreased.Conclusion:1、Human-derived BCMA CAR-T is effective in the treatment of RRMM,and CRS is controllable,2、Human-derived BCMA CAR-T may be effective in the treatment of EMM,3、Human-derived BCMA-targeted CAR-T is effective in the treatment of RRMM that has relapsed and progressed after mouse-derived CAR-T therapy,4、The CRS of human-derived BCMA-targeted CAR-T therapy is controllable and the safety is good.Part Ⅱ: Exploration of new biomarkers for CAR-T-related cytokine release syndromeObjectives:To identify the new biomarkers that can predict the occurrence of CRS in human-targeted BCMA CAR-T cell therapy,and to clarify the new biomarkers related to the severity of CRS.Method:Five patients who received human-targeted BCMA CAR-T RRMM were enrolled.According to the time points of D-1,D1,D3,D5,D7,D10,D14,peripheral blood was collected,and the concentration of cytokines was detected by immunomag-netic beads(Luminex)using 12 factor panel based on Luminex200 platform.Comprehensive analysis and comparison of the concentration changes of cytokines before and after CAR-T reinfusion,the detected cytokines include: G-CSF 、 GMCSF、IL-6、IL-8、TNF-α、Eotaxin、MCP-1、CRP、Granzyme A、PD-L1/B7-H1、CD40 Ligand、PDGF-AA.Outcome:1.MCP-1 and GM-CSF showed an upward trend in the first three days after CAR-T infusion.It can be speculated that MCP-1 and GM-CSF may predict the occurrence of CRS,2.GM-CSF,IL-6 and PDGF-AA may be related to the occurrence of grade 2/3CRS.Conclusion:1.MCP-1 and GM-CSF may predict the occurrence of CRS,2.GM-CSF、IL-6 and PDGF-AA may be related to the severity of CRS. |
