| Purpose(一)main purpose: 20 cases of relapsed and refractory multiple myeloma were treated with BCMA CAR-T cells to observe the clinical efficacy of BCMA CAR-T cell therapy.(二)Secondary objective: To observe the clinical safety of BCMA CAR-T cell therapy in 20 patients with relapsed and refractory multiple myeloma.MethodCollect the data and information of 20 patients with R/R MM treated with BCMA CAR-T cells from June 2018 to June 2020,and carry out clinical observation and research for 24 months,fully inform the patients and their families of their illness,prognosis,the general process of CAR-T cell treatment and the possible risks and benefits of the test,and sign the informed consent form after the screening entry criteria meet the requirements.On the 14 th day before reinfusion,the peripheral blood mononuclear cells of patients were collected and T cells were isolated.Then BCMA-CAR was expressed in T cells by genetic engineering and virus transfection,which were amplified and cultured in vitro.After culture,T cells fused for an average of 9 days(ranging from 8 to 10 days).All patients were given FC regimen before CAR-T infusion(Fludarabine 30 mg/m2,-5 ～-3 days;Cyclophosphamide 300mg/m2,-4 ～-3 days)was pretreated to clear lymphocytes,and then CAR-T cells were infused on the 0 th day.Before infusion,baseline indicators should be monitored,including venous blood(blood routine,blood biochemistry,serum protein electrophoresis,serum immunofixation electrophoresis,ferritin,coagulation factor),bone marrow(bone marrow morphology,MRD),and urine retention(urine routine,urine)Adverse reactions should be monitored on the 3rd,5th,7th,10 th,14th and 21 st day after infusion(detection of cytokine and CAR copy number,blood routine,blood biochemistry,myocardial enzyme,liver and kidney function,coagulation,electrolyte,CRP and ferritin).The changes of body temperature,blood oxygen,urine volume and blood pressure need to be detected every day.On the 28 th day after infusion,venous blood,bone marrow blood and urine should be taken for end point evaluation,and the evaluation standard is the standard of efficacy evaluation in NCCN guidelines.The diagnostic criteria of cytokine release syndrome(CRS)refer to the criteria proposed by Lee et al.Other adverse reactions were evaluated by WHO grading standards for acute and subacute adverse reactions of anticancer drugs.ResultsBCMA CAR-T is effective in the treatment of R/R MM.Eighteen of 20 patients ach ieved partial remission(PR),with an overall response rate of 90%(18/20),amon g which 2 patients achieved strict complete remission(s CR),accounting for 10%.10 patients achieved complete remission(CR),accounting for 50%.4 pati ents achieved very good partial response(VGPR),accounting for 20%.There were 2 patients with partial remission(PR),accounting for 10%.Cytokine rele ase syndrome(CRS)occurred in all 20 patients,and 13 cases(65%)had grad e 1 CRS.There were 4 cases of grade 2 CRS,accounting for 20%;Grade 3CRS occurred in 3 cases,accounting for 15%.Among the 20 patients treated with BCMA CAR-T,the most common adverse reactions in treatment-related a dverse events(AEs)were neutropenia with fever,decreased neutrophil count,d ecreased lymphocyte count and anemia.Followed by thrombocytopenia,leukope nia and pulmonary infection.There were 16 patients with anemia,accounting f or 80%.There were 15 patients with hematological adverse reactions of leukop enia,accounting for 75%;There were 12 patients with hematological adverse r eactions of thrombocytopenia,accounting for 60%;Lung infection occurred in8 cases,accounting for 40%.ConclusionBCMA CAR-T cell therapy is effective for RRMM,with controllable adverse reactions and good safety,which can be used as one of the effective and reasonable treatment schemes. |
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