Neutrophil-Lymphocyte Ratio and Monocyte-Lymphocyte Ratio Are Associated with Survival in Patients with Monoclonal Gammopathy of Undetermined Significance
Authors: Hsiao Virginia , Whitmore Colin , Cao Qing , Merino Aimee Marie , Ramesh Vidhyalakshmi , Teferra Andinet , Bachanova Veronika 
Published: December 2024

Background: Monoclonal gammopathy of undetermined significance (MGUS) is a pre-malignant clonal plasma cell disorder that impacts approximately 4% of the general population and is typically an incidental finding identified during an unrelated clinical work-up. Although asymptomatic, about 1% of MGUS patients will progress to multiple myeloma (MM) each year. Prior investigators have identified elevated neutrophil-lymphocyte (NLR) and monocyte-lymphocyte (MLR) ratios reflect suppressive immune system imbalance and correlate with poorer survival in patients with multiple myeloma (MM) and other malignancies. The impact of these biomarkers in patients with MGUS is unknown.

Methods: We searched a single institution's electronic medical records and identified consecutive patients with new diagnosis of MGUS diagnosed between 2011-2021. We recorded patients characteristics and incidence of progression to MM. Retrospective chart review was conducted to confirm diagnosis of MM. Our cohort included 1755 MGUS patients with age at diagnosis between 50-80 years. Patients were included if they had baseline CBC and available last follow up date. 75 patients experienced progression from MGUS to MM based on ICD 10 code (C90.00). We determined the NLR and MLR within 30 days of MGUS diagnosis. For patients who had CBCs collected in the context of acute infection, the next available values were used. Primary endpoints included progression free survival (PFS), MM progression by cumulative incidence, and overall survival (OS). PFS was evaluated via Kaplan-Meier. Recursive partitioning was used to identify the optimal cutoff based on PFS. Cumulative incidence of MM progression was estimated using Fine and Gray's competing risk analysis.

Results: Among 1755 eligible patients, median age was 68, 53% were male, and 86% were Caucasian. At median follow-up of 4.7 yrs (range 0-20.12 yrs), the cumulative incidence of progression to MM was 3% (95%CI 2- 4%). There were no significant differences in age, sex, race, and ethnicity between those who progressed to MM (n=78) and non-progressors (n=1677). Median NLR and MLR at the time of MGUS diagnosis were lower in progressors compared to non-progressors (NLR: 2.15 vs 2.75, p&lt;0.01), (MLR: 0.33 vs 0.38, p=0.04). Yet, by recursive partitioning, risk to MM progression was similar in cohorts with low vs high NLR and MLR (high ratio 2% vs low ratio 3%). Concurrently, time to MM progression was similar in groups with low vs high NLR (median 214 days vs 391 days, p=0.54) and MLR (median 239 vs 128 days; p=0.54).

However, patients with high (≥5) NLR and high (≥0.55) MLR at the time of MGUS diagnosis had significantly worse 3-year OS compared to patients with low NLR (OS: 63% [95%CI 57- 68%] vs 83% [95%CI 81- 85%] p&lt;0.01) and low MLR (OS: 64% [95%CI 59- 68%] vs 84% [95%CI 81- 85%], p&lt;0.01). Similarly, patients with high (≥5) NLR and high (≥0.55) MLR at the time of MGUS diagnosis had a lower 3 year PFS compared to patients with low NLR (PFS: 61% vs 80%, p&lt;0.01) and MLR (63% vs 81%, p&lt;0.01). Results of univariate and multivariate analyses will be reviewed.

Conclusion: Evaluation of neutrophil, monocyte and lymphocyte proportions at the time of MGUS diagnosis suggest that patients with NLR (≥5) and MLR (≥0.55) experience significantly worse PFS and OS, suggesting potential use of these biomarkers in assessing prognosis. Preliminary assessment of NLR and MLR showed lack of association with the risk of progression to MM. Additional analysis to further understand the causes of deaths and impact of neutrophil/monocyte/lymphocyte balance in patients with MUGS will be explored.