P-169: Tumor Associated Macrophages’ cytokines; CD163, CCL4 and CCL2, as possible new biomarkers for Overall Survival and Transformation in Smoldering Multiple Myeloma.

Introduction: Tumor associated macrophages (TAM) constitute a major part of the bone marrow microenvironment and play a pivotal role in growth of various hematologic malignancies, such as Multiple Myeloma (MM). Cytokines secreted by TAM, such as hemoglobin scavenger receptor CD163, Monocyte Chemoattractant Protein-1 (MCP1/CCL2), and Macrophage Inflammatory Protein (MIP/CCL4) can be detected in their soluble forms and reflect the TAM burden and function. Interactions between these cytokines and their levels correlate with disease progression and metastases risk, mainly in solid tumors. In our study, we aimed to investigate the clinical utility of those in patients with Smoldering Multiple Myeloma.

Methods: One hundred and sixty (160) patients were included in the study and clinical and laboratory characteristics were reviewed, after patients’ informed consent. Serum sCD163, CCL4 and CCL2 were tested in frozen sera collected at patients’ diagnosis in 19, 62 and 62 patients respectively, and in healthy individuals (HI) . Measurements were performed by ELISA (Duo-Set R&D Quantiquine) according to the manufacturer’s instructions. Their median age was 69 yrs (range, 34-86), 59% were women and 41% men. Median value of variables was used as the cut off point, except for CCL4, for which “detected” or “not-detected” was used. Median time to evolution (TTE) was 103 months (range,4-291), with a total of 13 patients (20%) evolving to symptomatic MM. Median overall survival (OS) was 108 months (range, 11-291). Statistical analysis was performed with the SPSS v.26 software.

Results: Median sCD163 was 26826 pg/ml (11831- 97286) in HI and 26443 pg/ml (18266 - 39088) in patients with SMM. Median CCL2 was 147.5 pg/ml (22-187) in HI and 176,5 pg/ml (17-9911) in patients. CCL4 was not detected in HI and was detected in 32% of the patients (0-9641pg/mL). Shorter time to treatment was observed in patients with a ratio of CD163/CCL4 above the median (p =0,053) (Figure 1) and a ratio of CCL2/CCL4 above the median (p=0,041) (Figure 2). Patients with a ratio of CCL2/CCL4 values above the median had a statistically significant decreased OS (p=0,051) (Figure 3).

Conclusions: Our findings reveal that cytokines related to TAMs burden could predict TTE in SMM, and seem to be indicators of OS, supporting that cells of the monocyte-macrophage lineage may play a role in disease pathophysiology and progression. sCD163, CCL2 and CCL4 could eventually prove to be significant biomarkers in SMM.