Abstract: Objective To investigate the effects of extramedullary diseases (EMD)and regulatory T cells (Tregs) on the treatment efficacy of B cell mature antigens (BCMA) chimeric antigen receptor T cells (CAR-T) in relapsed/refractory multiple myeloma (RRMM). Methods A total of 24 RRMM patients, who admitted to the Second Affiliated Hospital and the First Affiliated Hospital of Anhui Medical University and the First Affiliated Hospital of the University of Science and Technology of China from June 2019 to September 2021, were selected as the research objects. The treatment response and toxicity were observed and monitored after BCMA-CAR-T cell infusion. The overall remission rate (ORR), duration of response (DOR), follow-up of relapse-free survival (RFS) and overall survival (OS) were compared between the patient groups with and without EMD as well as of high and low Tregs levels. Results Within 2 months of BCMA-CAR-T cell infusion, the ORR of RRMM patients was 87.5%. The ORR of patients without EMD was better than that of patients with EMD (P=0.038), and Tregs levels did not affect the ORR of patients (P=0.876); With EMD and the abnormal increase Tregs reduced the duration of remission ( P=0.004, 0.001).The OS rate and RFS rate of patients with EMD were lower than those without EMD (60.0% vs 84.2%, P=0.013; 40.0% vs 57.9%, P=0.007); The OS rate of patients with abnormally high Tregs level was not significantly different from that of patients with normal or low Tregs level (P=0.077), but the RFS rate was significantly decreased (40.0% vs 77.8%, P=0.011). Univariable Cox regression analysis showed that OS and RFS of patients with EMD were shorter than those without EMD (HR=8.465, 95%CI: 1.150-62.315, P=0.036; HR=5.569, 95%CI: 1.332-23.285, P=0.019), RFS of patients with abnormally high Tregs level was also shorter than that of patients with normal or low Tregs level (HR=8.806, 95%CI: 1.088-71.282, P=0.017). There was no significant difference in the incidence of overall adverse events in BCMA-CAR-T cell therapy between the EMD group and the Tregs group (all P>0.05). Conclusions The efficacy and survival of BCMA-CAR-T cell therapy are worse in RRMM patients with EMD than those without EMD, and abnormal Tregs may be the root causes of its recurrence.

Key words: Multiple myeloma, B cell mature antigens, Chimeric antigen receptor T cells, Extramedullary diseases, Regulatory T tells, Relapsed, Refractory