| Purpose:Multiple myeloma(MM)is the second most common haematological cancer,which is generally a disease of older adults.In recent years,several new therapies for MM have prolonged survival of patients with MM,but cure for MM remains elusive.At present,the latest internationally targeted BCMA CAR-T cell clinical trial has achieved good results,but it is still necessary to expand the number of patients to further verify and explore the efficacy and safety targeting of BCMA CAR-T cells in patients with relapsed refractory multiple myeloma in China.Therefore,this study conducted a clinical trial of targeting BCMA CAR-T cells for the treatment of relapsed and refractory multiple myeloma to evaluate the safety and efficacy of BCMA CAR-T cells in Chinese MM patients.Recently,a number of studies have shown that gut microbiome may influence anti-tumor immune response by means of innate and adaptive immunity,gut microbiome could modulate response to anti-PD-1 immunotherapy in melanoma patients.In this study,we collected the fecal samples from different stages of CAR-T cell therapy in MM patients,compared the changes of intestinal microecology at different stages of MM patients receiving CAR-T cell therapy and explored their correlation with CAR-T cell efficacy and CRS severity.Methods:17 patients with relapsed refractory multiple myeloma received BCMA CAR-T cell infusion after pretreatment with FC regimen.By detecting the content of M protein in peripheral blood and urine of patients,flow detection of peripheral blood and bone marrow CAR-T cells and BCMA positive cells.The serum cytokine levels,blood routine,coagulation parameters and liver and kidney function were measured to evaluate the safety and efficacy of CAR-T cells.Taxonomic profiling using 16S ribosomal RNA(rRNA)gene sequencing was performed to detect the fecal samples at different stages of CAR-T cell treatment,The changes of intestinal flora diversity and composition before and after treatment with BCMA CAR-T cells were observed in patients with multiple myeloma.Resμlts:1、17 patients with relapsed refractory multiple myeloma received BCMA CAR-T cell therapy,9/17 patients(53%)achieved a complete remission,6/17(35%)achieved a very good partial remission and 2/17(12%)achieved a partial remission.The overall response rate was 100%,Cytokine release syndrome occurred in all patients,9/17 patients(53%)had grade<3cases,8/17 patients(47%)was grade 3 CRS.patients with less than grade 3 CRS were relieved after symptomatic treatment with non-steroidal anti-inflammatory drugs and prophylactic antibiotics.Patients with grade 3 CRS were significantly relieved after treatment with an IL-6 receptor antagonist,and vital signs were stable.No central nervous system toxicity occurred in this study.2、17 MM patients received BCMA CAR-T cell therapy,the diversity of intestinal flora in the stage of cytokine releasing syndrome(CRS1)was significantly reduced compared with that in the stage before CAR-T cell infusion(FC2).In addition,the intestinal flora diversity of MM patients was further reduced after undergoing cytokine release syndrome(CRS2)compared with that before cytokine release syndrome(CRSO)3、17 MM patients after CAR-T cell therapy showed significant differences in intestinal flora in different efficacy groups and different CRS grade groups.By detecting the intestinal flora of the CRS1 stage of 17 patients with MM,it is possible to predictthe efficacy of MM patients receiving CAR-T cell therapy.Conclμsion:1,BCMA CAR-T cells have good curative effect on relapsed and refractory multiple myeloma,and have good safety and controllable side effects.2,At different stages of CAR-T cell therapy in MM patients,the diversity and dominant flora of intestinal flora changed3,There were significant differences in the dominant intestinal flora of MM patients treated with CAR-T cells between different therapeutic groups and patients with different CRS grade. |
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