A Single-center,Open,One-arm Clinical Study Of The Safety And Efficacy Of Infusion Of Anti-BCMA CAR-T For Relapsed/Refractory/High-risk BCMA+ Tumors

Objective(1)Main purpose: To evaluate the safety of infusion of anti-BCMA CAR-T for relapsed/refractory/high-risk BCMA+ tumors.(2)Secondary purpose: To evaluate the clinical efficacy of infusion of anti-BCMA CAR-T for relapsed/refractory/high-risk BCMA+ tumors.Study design This study was approved by the institutional review board of Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,and registered with the Chinese Clinical Trial Registry(Chi CTR-OPC-16009113).It was a single-center,open and one-arm clinical study.Subject Subjects of the study were patients of BCMA+ tumors.Methods A 18-month prospective clinical observational study of 18 patients with R/R MM who were received anti-BCMA CAR-T cells infusion at Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology from March 2017 to October 2018 was done.Fistly,mononuclear cells of eligible patients were collected.Then anti-BCMA CAR-T cells were constructed and cultured by Wuhan Bio-Raid Biotechnology through genetic engineering method.Patients were received fludarabine 25mg/m2 and cyclophosphamide 20mg/kg for 3 days(day-4 to-2)as lymphodepletion chemotherapy.Anti-BCMA CAR-T cells were infused separately on successive days from day 0.The median effective anti-BCMA CAR-T cells totaled 1×10^7/kg,which was ranging from 5.4×10^6/kg to 2.5×10^7/kg.Indicators such as blood routine,liver function and kidney function,electrolytes,coagulation function,β-2 microglobulin,cytokines,ferritin,serum immunoglobulin,etc.were monitored before and after CAR-T cells infusion.All relevant indicators were monitored after CAR-T cells infusion for 30 days,60 days,90 days,120 days,150 days,180 days,270 days,360 days,540 days.All patients were followed up until they died,lost to follow-up,or disease progressed.Adverse events(AEs)were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events V4.03.Cytokine release syndrome(CRS)was graded as the scale proposed by Lee et al.Efficacy assessment was assessed by the International Myeloma Working Group(IMWG)2016 update criteria,and the data collected were processed by Graphpad prism7.0 software.P<0.05 indicated that the difference was statistically significant.Finally,the safety and clinical effectiveness of anti-BCMA CAR-T treatment of R/R MM were evaluated.Results Anti-BCMA CAR-T treatment allowed R/R MM patients to respond again.The overall response rate(ORR)was 88.9%(16/18).All patients experienced cytokine release syndrome(CRS).Fifteen patients underwent grade 1 to 2 CRS(83.3%),3 patients underwent grade 3 CRS(16.7%),and no one experienced grade 4 or above CRS(0%).Among the 18 R/R MM patients who received anti-BCMA CAR-T treatment,the most common treatment-related adverse events(AEs)were lymphopenia,neutropenia,and neutropenia with fever.Grade 3 or higher grade AEs occurred in more than 30% of patients including decreased lymphocyte counts(18/18,100%),decreased neutrophil counts(18/18,100%),leukopenia(17/18,94.4%),anemia(15/18,83.3%),thrombocytopenia(16/18,88.9%),CD4+ lymphopenia(18/18,100%),neutropenia with fever(18/18,100%)and pulmonary infection(7/ 18,38.9%).Conclusion It is safe and effective for R/R MM patients to receive anti-BCMA CAR-T cells therapy.