Background: Multiple myeloma (MM) is the second most prevalent hematologic malignancy. The prognosis of MM patients varies, with low-risk patients surviving more than 10 years with standard care and high-risk patients surviving less than 1 year. CAR-T therapy shows promising clinical results on relapsed or refractory MM (R/RMM) patients. However, generating clinically significant doses of CAR-T cells from heavily pre-treated patients for autologous CAR-T therapy is not always possible. Although allogeneic CAR-T cells therapy could potentially overcome such limitations, it poses a considerable risk of graft-versus-host disease (GVHD). Cord blood (CB) is a convenient source of T cells with clear advantages. T cells in CB have low immunogenicity and a relatively low risk of GVHD. Here we present a novel approach to CAR-T cells production from CB, which we hope could overcome the constraints mentioned above. Aims: The study aims to evaluate the safety and efficacy of the CB-generated BCMA-CAR-T infusion in R/RMM patients. Methods: This study is based on a clinical investigation during Jan 2021 and Dec 2021 in Shaanxi Provincial People’s Hospital. In this study, CD3+ T cells from the CB samples were selected, activated, and modified by lentivirus to produce anti-BCMA CAR-T cells. The cells were administrated intravenously to patients with R/RMM after expanding for 5-10 days in vitro. 2-3 days after being administered the lymphodepleting chemotherapy regimen of cyclophosphamide and fludarabine, patients received CAR-T cells infusion. We followed the occurrence of adverse events, the level of inflammatory cytokine concentration, CAR-T cells expansion in the peripheral blood, serum monoclonal protein levels, and the proportion of plasma cells in bone marrow smears after CAR-T cells infusion. Results: This study included 11 patients with R/RMM (7 males and 4 females). The median age was 58 years (ranging from 44 to 65). 18.2% (2/11) of the patients had received other CAR-T therapies and relapsed before the enrolment. 72.73% (8/11) of the patients had the extramedullary disease (EMD). 63.64% (7/11) of the patients had received autologous hematopoietic stem cell transplantation (Auto-HSCT). All patients received CAR-T infusion at the average dose of 7.11 (4.4-15) ×106/kg. After infusion, 18.2% (2/11) of the patients had a fever lasting for 48 hours, and 18.2% (2/11) of them had an increase in heart rate. Nausea and diarrhea occurred in 18.2% (2/11) of the patients. No patients had transient consciousness disorder. No patients received dexamethasone to relieve symptoms. CAR-T cells had expanded in all patients, with no increase in the levels of IL-6, IL-8 and IFN-r in peripheral blood in 2 weeks after infusion. Grade 1 cytokine release syndrome (CRS) was found in 2 patients. No patients had GVHD after infusion. The ORR was 54.5% (6/11), with 18.2% (2/11) of the patients achieving CR, and 36.4% (4/11) achieving PR. Except 1 female died from severe pulmonary infection, other 10 patients were followed up for more than 1 month. Unfortunately, 1 patient who reached CR relapsed during 3 months of follow-up. Those 4 patients who didn’t achieve PR received autologous CAR-T therapy afterwards and had responses better than PR (1 CR, 1 VGPR, 2 PR). Summary/Conclusion: BCMA-CAR-T cells manufactured from CB show a promising safety profile and certain clinical efficacy for R/RMM patients who are not eligible for autologous CAR-T cells therapy. We also found allogeneic CAR-T cells manufactured from CB could prepare patients for later subsequent autologous CAR-T therapy.