Objective ·To detect immunoglobulin (Ig) expression levels in newly diagnosed multiple myeloma (MM) patients before and after induction therapy, and to explore the clinical significance of Ig expression levels and their dynamic changes in relation to treatment efficacy, infection occurrence, and prognosis. Methods ·Clinical data from 142 MM patients treated at the Department of Hematology, The First Affiliated Hospital of Soochow University between August 2018 and September 2020 were analyzed. Baseline Ig expression levels and post-induction changes following bortezomib-lenalidomide-dexamethasone (VRD) regimen were assessed. Immunoparesis was defined as uninvolved Igs below the laboratory lower limit of normal. Patients were stratified by immunoparesis severity (mild, moderate, severe, extremely severe). ANOVA, rank-sum tests, and χ² tests were used to analyze correlations with baseline characteristics. The relationship between the improvement in immunoparesis and the induction efficacy, infection occurrence, and prognosis was analyzed based on the dynamic changes in immunoparesis. Results ·Normal Igs were severely reduced in newly diagnosed MM patients. Immunoparesis was present in 128 patients (90.1%), with severe or extremely severe immunoparesis accounting for 76.1%. Patients with extensive immunoparesis (all uninvolved Ig levels below the lower normal limit) were more likely to have severe immunoparesis (P<0.05). There were no statistically significant differences in age,gender, presence of severe renal insufficiency, and high-risk cytogenetics among MM patients with different degrees of immunoparesis (P>0.05), but there were statistically significant differences in MM staging (P=0.008) and typing (P=0.010). Most patients with severe immunoparesis were at stage Ⅱ/Ⅲ based on the Revised International Staging System (R-ISS) and were of the IgG type. At diagnosis, the levels of the involved Ig or light chain were negatively correlated with normal Ig levels (P<0.05). Improvement in immunoparesis after induction therapy was positively correlated with treatment response (P=0.006). The infection rate was high (26.8%), but no significant correlation was found between immunoparesis and infection occurrence (P>0.05). After induction therapy, patients showing improvement in immunoparesis had significantly longer progression-free survival (PFS) (median PFS: not reached vs 38 months, P=0.025), but no significant impact on overall survival (OS) was observed (P=0.450). Conclusion ·Immunoparesis is common and severe in newly diagnosed MM patients, with severity correlating with disease stage and subtype. VRD therapy can partially reverse immunoparesis, and improvement is positively associated with treatment response and PFS benefit. Infection risk appears unrelated to immunoparesis severity and warrants comprehensive prevention strategies. Humoral immune deficiency may serve as a prognostic indicator in MM, but its impact on OS requires further investigation.