Infusion of chimeric antigen receptor T cells against dual targets of CD19 and B-cell maturation antigen for the treatment of refractory multiple myeloma

摘要

Objective To investigate the safety and efficacy of chimeric antigen receptor T (CAR-T) cell infusion in patients with refractory multiple myeloma (MM). Methods Sixteen patients diagnosed with refractory MM were included in this study. Patients received initial infusions of T-derived CD19/B-cell maturation antigen (BCMA) CAR-T cells with 100% CD19, followed by second infusions with 40% BCMA and third infusions with 60% BCMA. The total doses were 0.5–1?×?10 ~(7)/kg CD19 and 1.2???6.2?×?10 ~(7)/kg BCMA. Patients were monitored after infusion. Levels of interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor-α, and C-reactive protein were determined by enzyme-linked immunosorbent assay. Results Cytokine release syndrome (CRS) was observed in all 16 patients. Thirteen patients with CRS stage II?IV had persistent hyperthermia from 5?14 days after infusion, while most patients developed hyperthermia from 1 day after infusion and their temperatures returned to normal within 2?10 days. Levels of all factors were significantly elevated 2 days after infusion, peaked at 5 days, and then gradually decreased to normal levels. All inflammatory factors showed normal levels by 10 days after infusion. Conclusion Body temperature and levels of inflammatory factors all increased dramatically after infusion of CD19/BCMA CAR-T cells, but recovered to normal levels after appropriate treatment and nursing.