From the Guidelines
Pembrolizumab should be discontinued when creatinine clearance falls below 15 mL/min. For patients with moderate renal impairment (creatinine clearance 30-59 mL/min) or severe renal impairment (creatinine clearance 15-29 mL/min), pembrolizumab can typically be continued without dose adjustment, but with careful monitoring 1. The drug is primarily eliminated through non-renal pathways, which explains why it can often be used in patients with compromised kidney function. However, when kidney function deteriorates to end-stage renal disease levels (creatinine clearance below 15 mL/min), the risk-benefit profile changes significantly. At this point, the potential for drug accumulation and adverse effects increases, while the patient's overall condition may make them less likely to benefit from immunotherapy. Additionally, patients receiving pembrolizumab should be monitored for immune-mediated nephritis, which can further compromise renal function and may require corticosteroid treatment and temporary or permanent discontinuation of the medication regardless of baseline creatinine clearance 1. Some key considerations for managing renal impairment in patients receiving pembrolizumab include:
- Monitoring serum creatinine prior to every dose of checkpoint inhibitor therapy 1
- Holding therapy while evaluating and treating other potential causes of renal dysfunction 1
- Considering renal biopsy to confirm etiology and guide management in suspected cases of immune-related renal disease 1
- Discontinuing therapy in the face of persistent or recurrent grade 2-3 adverse events, or emergence of grade 4 toxicity 1
From the Research
Discontinuation of Pembrolizumab due to Renal Toxicity
- The decision to discontinue pembrolizumab due to renal toxicity is based on the severity of the renal impairment and the patient's overall clinical condition 2, 3.
- There is no specific creatinine clearance value at which pembrolizumab should be discontinued, as the decision is individualized and depends on various factors, including the patient's underlying disease, comorbidities, and response to treatment.
- However, a study on predictors of short-term successful discontinuation of continuous renal replacement therapy found that a creatinine clearance of 11 mL/min was a predictor of successful discontinuation 4.
- In general, dose adjustment or discontinuation of medications may be indicated when the creatinine clearance falls below 30 mL/min 5.
- The mechanism of renal damage caused by pembrolizumab is often acute tubulointerstitial nephritis, and distinguishing the cause of renal failure is crucial to determine which drug can be safely continued and which drug must be halted 6.
Key Considerations
- Renal function should be closely monitored in patients receiving pembrolizumab, and the drug should be discontinued if severe renal toxicity occurs 2, 3.
- The use of corticosteroids may improve kidney function in patients with acute interstitial nephritis caused by pembrolizumab 2.
- A diagnostic and treatment algorithm based on clinical, laboratory, radiographic, and pathologic parameters can help clinicians diagnose the underlying cause of acute kidney injury in patients treated with pembrolizumab 6.