Monocytosis at Diagnosis Is Associated with Decreased Overall Survival in Patients with Newly Diagnosed Multiple Myeloma

Introduction: Multiple myeloma (MM) is an incurable hematologic malignancy caused by the neoplastic proliferation of plasma cells within the bone marrow. The tumor microenvironment within the bone marrow consists of a diverse array of immune cells which regulate MM cell proliferation and survival. Specifically, tumor-associated macrophages (TAMs) derived from peripheral blood monocytes migrate to the bone marrow where they support MM cell growth and promote resistance to apoptosis. Several studies suggest that the amount of bone marrow TAMs directly correlates with disease activity and worse clinical outcomes in MM. Considering that peripheral blood absolute monocyte count (AMC) could reflect the burden of bone marrow TAMs, we sought to determine the prognostic significance of AMCs at diagnosis of MM. Methods: Using the integrated nationwide VA electronic health records and VA Corporate Data Warehouse, patients were identified by International Classification of Diseases (ICD) codes for MM. Patients were required to have at least 3 visits with an MM ICD code on separate days, have received at least one MM drug with the exception of corticosteroids after the date of diagnosis and have 2 or more absolute monocyte counts measured by automated or manual differential at separate visits within 18 months before and 7 days after MM diagnosis. We further confirmed the date of diagnosis using the VA Cancer Registry. We excluded patients with aplastic anemia, myelodysplastic syndrome, chronic myelomonocytic leukemia and other myeloproliferative neoplasms. In this cohort, monocytosis was defined based on the institution’s cut-off as a sustained absolute increase in monocyte count of 0.8 (800/mm3) or greater with extreme monocytosis being greater than 1.25 (1250/mm3). Patients were stratified into three groups according to AMC at diagnosis, namely AMC 1.25. To avoid extreme values significantly affecting the analysis, the Kruskal-Wallis test was used to compare continuous variables between the groups. Chi-squared tests were used to compare categorical variables. Hazard estimates for the prognostic analysis were obtained via adjusted Cox proportional hazard models. Overall survival was estimated using the Kaplan-Meier method and log-rank tests were used to compare the survival of each group. Results: A total of 5,265 patients with MM were included in the final analysis with a median follow up of 2.9 years (range 1.3 - 5.2). At diagnosis of M