From the FDA Drug Label
The pharmacokinetics of avelumab as a single agent was characterized in patients who received BAVENCIO at doses ranging from 1 to 20 mg/kg every 2 weeks... No clinically meaningful differences in pharmacokinetics were observed in the clearance of avelumab based on age; body weight; sex; race; PD-L1 status; tumor burden; mild to severe renal impairment (calculated creatinine clearance of 89 to 15 mL/min, as estimated by the Cockcroft-Gault formula)
- No specific creatinine clearance value is provided in the drug label for discontinuing avelumab.
- The label mentions that no clinically meaningful differences in pharmacokinetics were observed in patients with mild to severe renal impairment (calculated creatinine clearance of 89 to 15 mL/min).
- Therefore, no conclusion can be drawn regarding the specific creatinine clearance value at which to discontinue avelumab 1.
From the Research
Avelumab should be discontinued when creatinine clearance falls below 30 mL/min. This recommendation is based on the drug's safety profile in patients with severe renal impairment, as there is limited clinical data on its use in patients with severe renal dysfunction 2. The concern with continuing avelumab in patients with severely compromised kidney function relates to potential altered drug clearance and increased risk of immune-related adverse events, such as acute interstitial nephritis (AIN), podocytopathy, and hyponatremia 3.
Key Considerations
- Regular monitoring of renal function is essential during avelumab treatment to promptly identify any decline in kidney function.
- If a patient's creatinine clearance improves to above 30 mL/min after temporary discontinuation, resumption of avelumab may be considered following careful evaluation of the risk-benefit profile and consultation with nephrology.
- The decision to discontinue or resume avelumab should always be individualized based on the patient's overall clinical status and treatment goals, taking into account the potential benefits of continued treatment versus the risks of adverse events.
Supporting Evidence
- A study published in 2023 reported the successful treatment of metastatic renal cell carcinoma in patients with end-stage renal disease undergoing dialysis using avelumab plus axitinib, with no severe adverse events identified 2.
- However, the majority of evidence suggests that avelumab should be used with caution in patients with severe renal impairment, and that discontinuation should be considered when creatinine clearance falls below 30 mL/min 4, 5, 6, 3.