PB1981: EFFICACY AND SAFETY OF DENOSUMAB IN PATIENTS WITH MULTIPLE MYELOMA

Background: Multiple Myeloma (MM) bone disease can lead to skeletal complications, including skeletal-related events, bone pain, and hypercalcemia. These complications can seriously affect the quality of life of patients and be life-threatening. Usually, the prevention of these complications uses Bisphosphonates (BP). Denosumab, a fully human monoclonal antibody, binds to RANKL to inhibit the formation, function and survival of osteoclasts, the cells responsible for bone resorption. A therapeutic alternative to BPs, Denosumab has become the preferred agent over Zoledronic acid because it is approved for use in people with kidney failure. We report our experience with the use of this new therapeutic class.

Aims: The aim of this study is to determine the efficacy of Denosumab in patients with MMand evaluate the tolerance of this molecule

Methods: This is a descriptive retrospective study for 4 years from 2015 to 2019, having collected 62 patients, 30% of all patients with MM, treated in the Hematology Department, CHU Annaba during the same period. The majority, 79% of patients were newly diagnosed. Data were collected from medical records, comorbidities and concomitant medications, clinical examination (bone events, Performans Status), with all the diagnostic workup. Denosumab was prescribed at a dose of 120 mg subcutaneously every 4 weeks, in combination with daily calcium and vitamin D supplementation. Adverse events were assessed according to the WHO rating.

Results: The patients are between 33 and 92 years old, the average age is 65, with a female predominance, the sex ratio is 0.82. The most frequent comorbidities are represented by arterial hypertension and diabetes. End-stage renal failure is present at diagnosis in 5 patients. The clinical picture is dominated by bone manifestations, anemic syndrome (81%) and renal failure. Protein electrophoresis most often revealed the gamma peak with the immunofixation of the IgG Kappa isotype. Symptomatic hypercalcemia (≥ 3 mmol/l) was found in 9 patients. Renal function is impaired in 50 patients (81%) including 13 at the stage of end-stage chronic renal failure. The majority of patients (71%) have an ISS III score. All patients are eligible for chemotherapy with a predominance for the VTD protocol. Denosumab is indicated both in newly diagnosed patients and in those (15 patients) previously treated with BP with an average of 6 monthly injections. The efficacy of Denosumab is assessed clinically (absence of bone pain) and no new radiological lesions, serum calcium dosage (spectacular efficacy) and renal function. All patients are evaluable for toxicity with grade ½ adverse effects. Grade ¾ hypocalcemia was noted in 4 of the 24 patients, and one case of osteonecrosis of the jaw (ONJ) ​​requiring definitive discontinuation of Denosumab. After a median follow-up of 17.23 months, 12 patients died, the major cause of which was progression of MM.

Summary/Conclusion: Denosumab is a new weapon in the prevention and treatment of bone disease. Its use is simpler (subcutaneous route), of similar efficacy and also more manageable depending on the renal insufficiency with a significant improvement in the quality of life