Abstract

Background: Multiple myeloma (MM) remains incurable, with drug resistance being a key clinical challenge. Impaired natural killer T (NKT) cell function may contribute to MM immune escape, while the significance of the inhibitory receptor CD161 expression on NKT cells is unclear. This study investigated the association between the peripheral blood CD3⁺CD56⁺CD161⁺ NKT cell proportion and response to bortezomib plus dexamethasone therapy in newly diagnosed MM (NDMM) patients.
Methods: Seventy-two NDMM patients receiving bortezomib plus dexamethasone and 37 healthy controls (HCs) were enrolled. Flow cytometry assessed the peripheral blood CD3⁺CD56⁺CD161⁺ cell proportion before and after treatment. Treatment response was evaluated according to IMWG criteria (responders: ≥ partial response [PR]; non-responders: ≤ stable disease [SD]). Receiver operating characteristic (ROC) curve analysis evaluated predictive value. Correlation with clinical parameters (ISS stage, LDH, β₂-MG, etc.) was analyzed.
Results: The baseline CD3⁺CD56⁺CD161⁺ proportion was significantly lower in NDMM patients than in HCs (2.25% vs. 4.20%, p < 0.05). After treatment, it increased to 3.10% (p < 0.05). Responders had a significantly higher baseline proportion than non-responders (3.40% vs. 1.60%, p < 0.0001). ROC analysis showed the baseline proportion predicted treatment response with an AUC of 0.789 (95% CI: 0.675 - 0.903). At the optimal cutoff of 1.85%, sensitivity was 87.9% and specificity was 71.8%. Patients with low proportions (< 1.85%) had a higher frequency of ISS stage III (p < 0.05) and significantly elevated LDH and β₂-MG levels (both p < 0.05).
Conclusions: Low expression of peripheral blood CD3⁺CD56⁺CD161⁺ NKT cells is associated with increased tumor burden and bortezomib resistance in NDMM, suggesting its potential as a predictive biomarker for treatment response.

DOI: 10.7754/Clin.Lab.2025.250744