P-070: Peripheral blood monocyte count is a dynamic prognostic biomarker for risk stratification in Multiple Myeloma

Abstract

<h3>Background</h3> Tumor-associated macrophages, derived from peripheral blood monocytes, support malignant plasma cell proliferation in the bone marrow (BM). Since peripheral blood absolute monocyte count (AMC) could reflect the BM microenvironment, we sought to evaluate the prognostic significance of AMC in multiple myeloma (MM). <h3>Methods</h3> We used nationwide Veterans Affairs electronic health records to include treatment-naive MM patients diagnosed between 2000 and 2019 without concomitant aplastic anemia, myelodysplastic syndrome, myeloproliferative neoplasm, and acute or chronic leukemia. We obtained AMC (×10^-3) closest to and within 90 days prior to each timepoint: at diagnosis and every 3 months from diagnosis up to 2.5 years. Patients were stratified by AMC: low (1.25). Our selection criteria excluded any treatment-related change in AMC. Overall survival (OS) was evaluated using Kaplan-Meier estimator and logrank tests. Cox models were used for multivariable analysis. <h3>Results</h3> We identified and analyzed 10,822 patients (median age 70 years; interquartile range [IQR] 63-77) with a median follow up of 2.9 years (IQR 1.3-5.3). At diagnosis, 25.3% of patients presented with abnormal AMC. Patients with low, severely elevated, elevated, and normal AMC at diagnosis had median OS of 2.3, 2.7, 3.1, and 3.6 years (p<0.001), respectively. Abnormal AMC 1 year or more after diagnosis was associated with inferior OS (median OS at 2.5 years; 2.0, 2.6, 3.4, and 3.9 years [p<0.001] in patients with low, severely elevated, elevated, and normal AMC, respectively). If patients with normal AMC at diagnosis developed an abnormal AMC 1 year or more after diagnosis, median OS was decreased relative to patients who maintained normal AMC. Notably, median OS improved across all AMC groups for patients with MM diagnosed after 2012 when modern therapies became standard of care. After adjusting for known prognostic factors (age, ISS Stage, LDH, creatinine), multivariable analysis showed similar results, with a significant association of OS with AMC at diagnosis and AMC measured up to 2.5 years after diagnosis. Hazard ratios (HRs) at diagnosis were 1.28 (95% confidence interval [CI] 1.06–1.41; p<0.001), 1.10 (95%CI 1.04–1.17; p=0.002), and 1.19 (95%CI 1.06–1.34; p=0.004), and HRs 2.5 years after diagnosis were 1.53 (95%CI 1.22–1.93; p<0.001), 1.11 (95%CI 1.00–1.23; p=0.043, 1.58 (95%CI 1.22–2.04; p<0.001) for low, elevated and severely elevated AMC, respectively. <h3>Conclusion</h3> Abnormal AMC in MM at diagnosis or follow up is significantly associated with inferior OS, independent of known prognostic factors. Survival was also inferior for patients who had normal AMC at diagnosis and developed abnormal AMC during follow up, possibly suggesting changes in the BM microenvironment. Overall, AMC is a readily available metric that could be included in the risk stratification of MM at diagnosis and beyond.