Efficacy And Safety Of Targeted BCMA CAR-T Therapy For Relapsed/refractory Multiple Myeloma

Objective:To evaluate the clinical efficacy,survival and safety of BCMA-targeted CAR-T in the treatment of relapsed/refract-ory multiple myeloma(R/RMM),and analyze its influencing factors.Methods:Through a retrospective study,the complete clinical data of 72 patients w-ith R/RMM who received targeted BCMA CAR-T therapy in the Department of Hemato-logy,Shaanxi Provincial People’s Hospital from March 2021 to February 2022 were coll-ected,and CAR-T cells were analyzed.Culture infusion,treatment effect,adverse reacti-ons,changes in the condition of follow-up treatment,and factors affecting the curative e-ffect,etc.The collec-ted data were statistically analyzed by SPSS26.0 software,and grap-hs were drawn by Gr-aph Pad prism9.0 software.When P<0.05,the difference was stati-stically significant.Results:1.Among the 72 R/RMM patients who received CAR-T therapy,there were 46 males and 26 females;the median age was 55(38～75)years old,and the age>65 years accounted for 13.9%(10/72);37 patients were Ig G type,10 cases of Ig A type,11 cases of Ig D type,and 14 cases of light chain type;40.3%(29/72)with extramedullary lesions,43.1%(31/72)with high tumor burden(bone marrow plasma cell ratio>30%),previous The median number of treatment lines was 4(2～12)lines,44.4%(32/72)had received hematopoietic stem cell transplantation,15.3%(11/72)had received BCMA CAR-T therapy,25.0%(18/72)had received The patients were complicated with renal insufficiency before infusion,and the median follow-up time after treatment was 7.2(0.1～12.3)months.2.Before infusion of CAR-T cells,68.1%(49/72)received cyclophosphamide(CTX)-based preconditioning,and 31.9%(23/72)received daratumumab(DARA)sequence Through CTX-based preprocessing.After collecting autologous peripheral blood cells,after 9.2(7～15)days of in vitro culture and expansion,the number of CAR-T positive cells infused was 11.5×10~6(1.2×10~6～2.2×10~7)/kg.3.Among the 64 patients with evaluable efficacy,the overall response rate(ORR)of1 month,3 months,6 months,and more than 6 months after CAR-T cell therapy were90.6%,96.7%,84.2%,and 82.7%,respectively..Stringent complete response(s CR)/CR rates were 18.8%,45.9%,68.4%,and 72.4%,respectively.Very good partial response(VGPR)rates were 34.3%,41.0%,15.8%,and 10.3%,respectively.Analysis of the factors affecting the efficacy showed that the ORR of Ig D patients after CAR-T reinfusion was only 42.9%,which was significantly lower than that of Ig G,Ig A and light chain patients.The ORRs of the latter three were 100.0%,100.0%and 77.8 respectively.%(P=0.003).4.The median disease-free survival(DFS)of the 72 patients was 3 months,and the median overall survival(OS)had not yet been reached.The estimated 1-year DFS rate and OS rate were 48.9%and 84.3,respectively.%,univariate analysis found that gender and plasma cell ratio were associated with OS,and multivariate Cox regression analysis found that bone marrow plasma cell ratio>30%was an independent risk factor for OS in all patients(P=0.017);64 cases could be evaluated for efficacy The median DFS and median OS of the patients were not reached during the follow-up period.The estimated 1-year DFS rate and OS rate were 81.5%and 94.9%,respectively.Univariate analysis found that age was related to the patient’s DFS and OS.Extramedullary infiltration,reinfusion 3-month remission status after CAR-T was associated with OS,and multivariate Cox regression analysis found that age>65 years was an independent risk factor for OS in 64 evaluable patients(P=0.044).5.Among the 72 patients,95.7%(69/72)had cytokine release syndrome(CRS),of which 69.4%(50/72)had grade 1 CRS and 8.3%(6/72)had grade 2 CRS,grade 3 CRS occurred in 6.9%(5/72),and grade 5 CRS occurred in 11.1%(8/72)with early death.CRS severity was associated with bone marrow plasma cell ratio(P=0.002);12.5%(9/72)patients developed CAR-T-cell-related encephalopathy(CRES),9.7%(7/72)Patients had grade 1 CRES,and 2.8%(2/72)had grade 2 CRES.Conclusion:The BCMA-targeted CAR-T treatment of R/RMM in various disease states is effective,and the treatment-related adverse reactions are basically controllable.Male,age>65 years,abnormal Ig D type immunoglobulin,high proportion of plasma cells in bone marrow before CAR-T treatment(>30%),and extramedullary infiltration were negative factors affecting the efficacy of CAR-T.Note that the number of positive CAR-T cells has no significant effect on the effect of CAR-T therapy.