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A 75-year-old patient with MM and moderate renal impairment (CrCl 45 mL/min) has been receiving denosumab 120 mg SC monthly for 1 year. They report recurrent skin infections, a potential side effect, and wish to explore stopping denosumab. Their myeloma is currently stable on maintenance therapy.
Questions and Answers:
1. True/False: Denosumab can be safely discontinued immediately without any specific precautions related to bone health.
Answer: False.
Explanation: Discontinuation of denosumab necessitates administration of at least one dose of an intravenous bisphosphonate to prevent rebound osteoclast activity. This rebound can lead to rapid bone loss and increased fracture risk.
2. True/False: Recurrent infections are a recognized potential complication associated specifically with denosumab therapy.
Answer: True.
Explanation: Infections are a potential toxicity associated with denosumab, distinct from the typical side effect profile of bisphosphonates.
3. True/False: Given the patient's CrCl of 45 mL/min, zoledronic acid would be absolutely contraindicated as the bridging therapy upon denosumab discontinuation.
Answer: False.
Explanation: While denosumab is preferred for initial treatment with CrCl ≤60 mL/min, zoledronic acid can be used cautiously in patients with renal impairment, often with a longer infusion time (e.g., 30-60 minutes). It could be considered as the bridging therapy if deemed appropriate after risk/benefit assessment.
4. Yes/No: If denosumab is stopped and a bisphosphonate dose is given, is the patient required to continue long-term bisphosphonate therapy thereafter?
Answer: No.
Explanation: The single dose (or potentially more, depending on clinical judgment) of bisphosphonate is primarily intended to mitigate the acute rebound effect of stopping denosumab. The decision regarding long-term osteoclast inhibitor therapy would depend on the overall clinical picture and expert recommendations concerning duration (e.g., having completed at least 2 years, patient stability).
5. Yes/No: Does the mechanism of denosumab involve direct incorporation into the bone matrix like bisphosphonates?
Answer: No.
Explanation: Denosumab is a monoclonal antibody that inhibits RANKL, thereby suppressing osteoclast formation and activation. Bisphosphonates, in contrast, incorporate into the bone matrix and directly affect osteoclasts.
6. Yes/No: Was denosumab shown to be superior to zoledronic acid in preventing SREs in the large head-to-head trial involving 1718 MM patients?
Answer: No.
Explanation: The large randomized trial comparing denosumab versus zoledronic acid in previously untreated MM found a similar time to first SRE and overall survival between the two treatment arms.
7. Drop Down Question: What phenomenon must be prevented by administering a bisphosphonate dose when denosumab is discontinued?
Acute phase reaction
Rebound osteoclast activity
Medication-related ONJ
Answer: Rebound osteoclast activity
Explanation: Stopping denosumab can lead to a rebound increase in osteoclast activity, causing rapid bone loss and fracture risk. This effect is mitigated by administering a bisphosphonate dose.
8. Drop Down Question: If zoledronic acid is chosen as the bridging agent after stopping denosumab in this patient (CrCl 45 mL/min), what modification to its administration is typically employed to potentially reduce nephrotoxicity risk?
Lower dose
Longer infusion time
Pre-hydration only
Answer: Longer infusion time
Explanation: For patients with renal impairment receiving zoledronic acid, using a longer infusion time (e.g., 30-60 minutes instead of at least 15 minutes) is a strategy used to decrease the maximum serum concentration and potentially lower the risk of nephrotoxicity.
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Ranjan Pathak
Founder, HemOncBytes | ReviewBytes