Hypercalcemia caused by humoral effects and bone damage indicate poor outcomes in newly diagnosed multiple myeloma patients.

Background: Hypercalcemia of malignancy (HCM) is a serious metabolic complication, and the highest rates are in multiple myeloma (MM). The cause of hypercalcemia in newly diagnosed multiple myeloma (NDMM) remains unknown. We sought to evaluate the prognostic impact and mechanism of hypercalcemia in patients with symptomatic NDMM.

Methods: We studied all consecutive MM patients who were initially diagnosed and followed up at Beijing Jishuitan Hospital between February 2013 and December 2019; 357 patients were included in the retrospective analysis.

Results: A total of 16.8% of MM patients presented with hypercalcemia at the time of MM diagnosis. The presence of hypercalcemia was associated with higher serum levels of β2 microglobulin, creatinine, phosphorus, uric acid, procollagen I N-terminal peptide, β-carboxy-terminal cross-linking telopeptide of type I collagen and osteocalcin, lower serum levels of hemoglobin, parathyroid hormone (PTH), and advanced ISS and R-ISS stages. Multivariate analysis showed that serum PTH, hemoglobin, creatinine, and uric acid levels were the main factors affecting hypercalcemia. The presence of hypercalcemia was associated with significantly inferior survival (40 months vs 57 months, p < 0.05) based on univariate analysis, and it remained an independent poor prognostic factor (HR: 1.854, 95% CI: 1.006-3.415, adjusted p = 0.048) in a multivariate model that included age and R-ISS stage.

Conclusion: This study shows that hypercalcemia is associated with poor survival and is caused by manifold factors with humoral effects and local bone destruction.