Abstract: Background　Plasma cell neoplasms remain incurable, with survival rates progressively declining with age. Particularly in elderly patients with multiple myeloma (MM), severe immunodeficiency and multiple comorbidities significantly worsen prognosis. There is a lack of research on long-term tolerated, gentle adoptive immunotherapy for elderly patients with plasmacytoma.Objective　To investigate the long-term efficacy and safety of adoptive mixed lymphocyte (mixT) immunotherapy based on CD16 antibody pre-activation for plasma cell neoplasms.Methods　This study enrolled 6 patients with plasmacytoma who received long-term regular mixT immunotherapy at the Department of Hematology, the Second Medical Center of PLA General Hospital from January 1, 2009 to December 30, 2024, including 4 MM cases, 1 smoldering myeloma (SMM) case, and 1 case of macrofocal multiple myeloma (MFMM). MixT cells meeting quality standards were administered to patients intravenously. Infusions were performed once per month for more than 12 cycles. The phenotypes of patients' mixT cells were observed by flow cytometry, Kaplan-Meier methods were applied to plot survival curves and assess disease status, and quality of life and tumor markers before and after infusion were measured by T-test, and adverse reactions were monitored.Results　Among the 6 patients, the median age at initial diagnosis was 65.5 (range: 52-77) years, and the median age at the last follow-up was 80.5 (range: 55-84) years. The median number of infusions administered was 53 (range: 18-189). After culture, the proportions of CD3+ T cells, CD8+ T cells, and NKT cells were significantly higher than those before culture. The median progression-free survival (PFS) and overall survival (OS) were not reached. As of December 30, 2024, 1 patient died due to disease progression, 4 achieved complete response (CR), and 1 achieved strict complete response (sCR). The 2-year PFS rate was 83.3%, and the 2-year OS rate was 83.3%. After 12 courses of mixT cell infusion, patients showed improved quality of life, with a decrease in β2-microglobulin (P＜0.01). LDH showed a downward trend without significant difference. Bone destruction in 1 patient with MFMM was significantly improved after mixT therapy. Transient low-grade fever and/or fatigue occurred occasionally during infusions. Conclusion　Preliminary exploration indicates that mixT, as a safe and effective adoptive immunocyte therapy, long-term mixT treatment may help middle aged and elderly patients with plasmacytoma enhance immune function, promote disease remission, improve quality of life, alleviate bone destruction, and improve long-term prognosis.