Romosozumab for the Management of Myeloma-related Bone Disease in Postmenopausal Women with Multiple Myeloma and Osteoporosis, REMOLD-MM Trial

Inclusion Criteria

• Documented multiple myeloma (MM) per International Myeloma Working Group diagnostic criteria (evidence of myeloma defining event attributed to underlying plasma cell disorder): * Clonal plasma cells in the bone marrow >= 10% or presence of a biopsy proven plasmacytoma; and * Any one or more of the following myeloma defining events: ** Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder: *** Hypercalcemia: serum calcium > 0.25 mmol/L ( > 1 mg/dL) higher than the upper limit of normal or > 2.75 mmol/L ( > 11 mg/dL) *** Renal insufficiency: creatinine clearance < 40 mL/min or serum creatinine 177 umol/L ( > 2 mg/dL) *** Anemia: hemoglobin > 2 g/dL below the lower limit of normal, or a hemoglobin value < 10 g/dL *** Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET/CT ** Clonal bone marrow plasma cell percentage >= 60%; or ** Involved: uninvolved serum free light chain (FLC) ratio >= 100 (involved FLC level be >= 10 mg/dL; or ** > 1 focal lesion on MRI studies (at least 5 mm in size)
• Presence of lytic bone lesion(s) due to MM based on radiographic evidence with at least one measurable lesion ( >= 0.5 cm in its largest diameter by computerized tomography [CT])
• Postmenopausal female, defined as last menstrual cycle at least 12 months prior to study enrollment
• Must have one of the following: * Osteoporosis on dual X-ray absorptiometry (DXA) scan; or * Fragility fracture of the spine or hip; or * Morphometric spine fracture; or * Osteopenia with elevated risk of fracture (calculated by the fracture risk assessment tool [FRAX] online calculator)
• Within 12 months prior to study entry, =< 4 doses of prior intravenous (IV) bisphosphonate with the last dose >= 3 months prior to study entry
• Prior oral bisphosphonates are allowed if the last dose was >= 3 months prior to study entry
• Prior denosumab use is allowed for the following: * For patients who received =< 5 consecutive doses of denosumab with the last dose of denosumab received >= 3 months prior to study entry. * For patients who received „d 6 doses of denosumab, IV bisphosphonate should be given at least 1 month after the last dose of denosumab (if the last dose of denosumab was within the past 2 years). Patients are then eligible >= 3 months after IV bisphosphonate is received. If >= 2 years have elapsed since the last dose of denosumab, IV bisphosphonate is not required, and patients are eligible for the study.
• Signed informed consent form(s). Individuals with impaired decision-making capacity may enroll if legally authorized representatives consent on behalf of individuals with impaired decision-making capacity
• Ability to comply with all study-related procedures in the investigator’s judgment
• 18 years of age or older

Exclusion Criteria

• Assigned male at birth
• Received teriparatide or other parathyroid hormone (PTH) analog use within 12 months prior to study entry
• Receiving concurrent antiresorptive therapy
• History of cardiovascular event (myocardial infarction and/or stroke) within the past 12 months of study entry
• History of non-healed dental or oral surgery
• History of osteonecrosis of the jaw
• 25-hydroxy vitamin D (25 [OH] vitamin D) levels < 20 ng/mL. Vitamin D repletion will be permitted and subjects may be rescreened once 25 (OH) vitamin D level >= 20 ng/mL
• Current hyper- or hypocalcemia, defined as albumin-adjusted serum calcium outside the normal range per institutional standard (< 8.5 or > 10.5 mg/dL)