Background: Chimeric antigen receptor engineered T cell (CAR-T) is a novel immunotherapeutic approach for cancer treatment and has been clinically validated in the treatment of acute lymphoblastic leukemia (ALL). Here we report an encouraging breakthrough of treating multiple myeloma (MM) using a CAR-T designated LCAR-B38M CAR-T, which targets principally BCMA. Methods: A single arm clinical trial was conducted to assess safety and efficacy of this approach. A total of 19 patients with refractory/relapsed multiple myeloma were included in the trial. The median number of infused cells was 4.7 (0.6 ~ 7.0) × 10e6/ kg. The median follow-up times was 208 (62 ~ 321) days. Results: Among the 19 patients who completed the infusion, 7 patients were monitored for a period of more than 6 months. Six out of the 7 achieved complete remission (CR) and minimal residual disease (MRD)-negative status. The 12 patients who were followed up for less than 6 months met near CR criteria of modified EBMT criteria for various degrees of positive immunofixation. All these effects were observed with a progressive decrease of M-protein and thus expected to eventually meet CR criteria. In the most recent follow-up examination, all 18 survived patients were determined to be free of myeloma-related biochemical and hematologic abnormalities. One of the most common adverse event of CAR-T therapy is acute cytokine release syndrome (CRS). This was observed in 14 (74%) patients who received treatment. Among these 14 patients there were 9 cases of grade 1, 2 cases of grade 2, 1 case of grade 3, and 1 case of grade 4 patient who recovered after treatments. Conclusions: A 100% objective response rate (ORR) to LCAR-B38M CAR-T cells was observed in refractory/relapsed myeloma patients. 18 out of 19 (95%) patients reached CR or near CR status without a single event of relapse in a median follow-up of 6 months. The majority (14) of the patients experienced mild or manageable CRS, and the rest (5) were even free of diagnosable CRS. Based on the encouraging safety and efficacy outcomes, we believe that our LCAR-B38M CAR-T cell therapy is an innovative and highly effective treatment for multiple myeloma.