Pb2142: serum osteocalcin as a predictor for the risk of denosumab and bisphosphonate induced hypocalcemia in myeloma patients with hypercalcemia

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: In our recent publication (Bao Li, 2020), we have reported that a total of 16.8% of myeloma patients presented with hypercalcemia at the time of myeloma diagnosis, with significantly inferior survival. Bone-modifying agents (denosumab, bisphosphonate) are essential in the effective treatment of hypercalcemia secondary to myeloma (Roodman GD. 2009). As a result, patients are also at increased risk of the important toxicities of hypocalcemia. Therefore, better biomarkers for predicting the risk of bone-modifying therapies-induced hypocalcemia in myeloma patients with hypercalcemia are urgently needed. Aims: To investigate if bone turnover markers especially serum osteocalcin could be potential predictor for the risk of hypocalcemia induced by denosumab or bisphosphonate in myeloma patients with hypercalcemia. Methods: We did a retrospective review of the medical records of patients with newly diagnosed multiple myeloma (NDMM) who received subcutaneously 120 mg of denosumab or 30-90mg of pamidronate or 4mg of zoledronate for monthly treatment of severe or symptomatic hypercalcemia secondary to NDMM. Forty-eight patients were identified from the inpatient medical record system at the Department of Hematology, Beijing Jishuitan Hospital and the median follow-up was 1 month. Bone turnover markers including OC(osteocalcin), P1NP (type 1 procollagen amino-terminal propeptide), β-CTX (bone resorption C-terminal telopeptides), PTH(parathyroid hormone), 25(OH) VD (25-hydroxy vitamin D). The serum samples were measured for bone turnover markers by using electrochemiluminescence immunoassays (Roche Diagnostics GmbH, Sandhofer Strasse). Results: Of the 48 NDMM patients presented with hypercalcemia at the time of myeloma diagnosis, 21 cases with denosumab treatment, 27 cases with bisphosphonates (3 cases of zoledronic acid and 24 cases of pamidronate acid) treatment. The incidence of treatment-induced hypocalcemia were 80.9% and 70.3% in the group with denosumab vs bisphosphonate (P＞0.05). The incidence of hypocalcemia at or over grade 3 were 19.0% and 3.7% in the group with denosumab vs bisphosphonate, respectively (P=0.106). The median time to the lowest serum calcium were 15 (range 7–30 days) day and 7 (range 6-7 days) day in the group with denosumab and the group with bisphosphonate, respectively. The median time for blood calcium returned to normal were 5 day (range 3-9 days) and 3 day (range 3–5 days) in the group with denosumab and the group with bisphosphonate. The serum osteocalcin level at diagnosis was significantly correlated with the serum corrected calcium level on the both day15（P=0.025） and day31（P=0.004）in the two groups. While β-CTX level at diagnosis was only significantly correlated with the serum corrected calcium level on the day31 (P=0.048). Other markers of bone turnover were not significantly correlated with post-treatment calcium levels. Summary/Conclusion： NDMM patients with hypercalcemia may increase the risk of hypocalcemia after treatment. Monitoring serum osteocalcin in NDMM at diagnosis may help to predict the potential hypocalcemia occurred at the first month.Keywords: Multiple myeloma, Zoledronate