What baseline labs should be ordered for a patient with stage IV renal cell carcinoma and impaired renal function before starting pembrolizumab (Pembrolizumab) and lenvatinib (Lenvatinib)?

Baseline Laboratory Testing Before Starting Pembrolizumab and Lenvatinib

Before initiating pembrolizumab plus lenvatinib in patients with stage IV renal cell carcinoma and impaired renal function, obtain a comprehensive metabolic panel, complete blood count with differential, thyroid function tests, urinalysis with urine protein quantification, lipid panel, and coagulation studies.

Essential Baseline Laboratory Tests

Chemistry Panel

Based on the most common laboratory abnormalities observed in the CLEAR trial, the following chemistry tests are critical 1:

• Lipid panel: Hypertriglyceridemia occurred in 80% of patients (15% Grade 3-4) and hypercholesterolemia in 64% (5% Grade 3-4) receiving lenvatinib plus pembrolizumab 1
• Pancreatic enzymes: Lipase elevation occurred in 61% (34% Grade 3-4) and amylase elevation in 59% (17% Grade 3-4) 1
• Renal function: Creatinine elevation occurred in 61% (5% Grade 3-4), which is particularly important given the patient's baseline impaired renal function 1
• Liver function tests: AST elevation in 58% (7% Grade 3-4), ALT elevation in 52% (7% Grade 3-4), and alkaline phosphatase elevation in 32% (4% Grade 3-4) 1
• Electrolytes: Hyperkalemia (44%), hyponatremia (41% with 12% Grade 3-4), hypocalcemia (30%), hypophosphatemia (29% with 7% Grade 3-4), and hypomagnesemia (25%) 1
• Glucose: Hyperglycemia occurred in 55% (7% Grade 3-4) and hypoglycemia in 44% (2% Grade 3-4) 1
• Albumin: Decreased albumin in 34% (0.3% Grade 3-4) 1
• Creatine phosphokinase: Elevation in 24% (6% Grade 3-4) 1

Hematologic Tests

Complete blood count with differential is essential, as the following abnormalities were observed 1:

• Lymphopenia: 54% of patients (9% Grade 3-4) 1
• Thrombocytopenia: 39% (2% Grade 3-4) 1
• Anemia: 38% (3% Grade 3-4) 1
• Leukopenia: 34% (1% Grade 3-4) 1
• Neutropenia: 31% (4% Grade 3-4) 1

Thyroid Function Tests

Thyroid dysfunction is common with this combination 1:

• TSH and free T4: Hypothyroidism occurred in 46% of patients receiving lenvatinib plus pembrolizumab 1
• Establish baseline thyroid function to distinguish treatment-related thyroid dysfunction from pre-existing disease 2

Urinalysis and Protein Quantification

• Urine protein-to-creatinine ratio or 24-hour urine protein: Proteinuria occurred in 29% of patients (7% Grade 3-4) 1
• This is critical for monitoring given the patient's baseline renal impairment 2

Coagulation Studies

• PT/INR and aPTT: Hemorrhagic events occurred in 32% of patients receiving lenvatinib plus pembrolizumab 1
• Baseline coagulation parameters help assess bleeding risk 2

Critical Monitoring Considerations for Impaired Renal Function

Given the patient's impaired renal function, special attention must be paid to 1:

• Baseline creatinine clearance calculation: 61% of patients experienced creatinine elevation, with acute kidney injury, renal failure, and renal impairment documented 1
• Electrolyte abnormalities: Hyperkalemia (44%) and hyponatremia (41%) are particularly concerning in patients with baseline renal dysfunction 1
• Proteinuria monitoring: Establish baseline protein excretion as nephrotic syndrome has been reported 1

Hepatotoxicity Screening

Grade ≥2 increased ALT or AST was reported in 18% of patients, with 31% of those requiring ≥40 mg daily oral prednisone equivalent 1. Baseline liver function is essential to:

• Detect pre-existing hepatic dysfunction 1
• Establish a reference point for monitoring treatment-related hepatotoxicity 2
• Identify patients who may require dose modifications 1

Common Pitfalls to Avoid

• Failing to obtain baseline lipid panel: With 80% experiencing hypertriglyceridemia, missing baseline values prevents accurate assessment of treatment-related changes 1
• Inadequate renal function assessment: In patients with impaired renal function, failure to establish baseline creatinine and proteinuria prevents early detection of treatment-related nephrotoxicity 1
• Omitting thyroid function tests: Nearly half of patients develop hypothyroidism, and baseline testing is essential for distinguishing treatment-related from pre-existing thyroid disease 1, 2
• Not checking pancreatic enzymes: Lipase and amylase elevations are common (61% and 59% respectively) and can be severe 1