From the Guidelines
Laboratory monitoring for patients on ipilimumab and nivolumab should include baseline and regular assessment of liver function tests (AST, ALT, total bilirubin), thyroid function tests (TSH, free T4), complete blood count, comprehensive metabolic panel, lipase, amylase, and cortisol levels, as recommended by the most recent guidelines 1. These parameters should be checked before each treatment cycle, typically every 2-3 weeks during combined therapy, and then monthly during maintenance therapy.
- More frequent monitoring may be necessary if abnormalities are detected.
- Particular attention should be paid to liver enzymes as hepatotoxicity is common, thyroid function as both hypothyroidism and hyperthyroidism can occur, and cortisol levels to detect adrenal insufficiency.
- Blood glucose should also be monitored for immune-mediated diabetes. These monitoring parameters are crucial because ipilimumab and nivolumab are immune checkpoint inhibitors that can cause immune-related adverse events affecting multiple organ systems, as reported in studies 1.
- Early detection of these abnormalities allows for prompt intervention with corticosteroids or hormone replacement therapy when needed, potentially preventing progression to more severe toxicity while maintaining cancer treatment efficacy. The American Society of Clinical Oncology clinical practice guideline also emphasizes the importance of monitoring for immune-related adverse events, including musculoskeletal symptoms, such as arthralgia and myalgia, and myositis 1.
- The guideline recommends routine assessment of serum inflammatory markers, autoantibodies, and imaging studies as needed to diagnose and manage these adverse events. However, the most recent and highest quality study 1 provides the most up-to-date recommendations for laboratory monitoring parameters, which should be prioritized in clinical practice.
From the FDA Drug Label
Table 21: Laboratory Values Worsening from Baselinea Occurring in ≥10% of Patients on YERVOY and Nivolumab - CHECKMATE-648 Laboratory Abnormality YERVOY and Nivolumab(n=322)Cisplatin and 5-FU(n=304) Grades 1-4 (%)Grades 3-4 (%)Grades 1-4 (%)Grades 3-4 (%) Hematology Anemia 52 7 66 14 Lymphopenia 50 13 44 8 Neutropenia 13 1.3 48 13 Thrombocytopenia 12 1.0 29 2.8 Chemistry Hyponatremia 45 11 40 8 Hyperglycemia 43 4.3 36 0.8 Increased AST 39 6 11 1.4 Increased ALT 33 6 8 0.7 Hypocalcemia 32 0 23 0.7 Increased alkaline phosphatase 31 3. 3 15 0 Hyperkalemia 23 1.6 24 0.7 Hypokalemia 19 5 17 6 Hypercalcemia 15 2.0 8 0 Hypoglycemia 15 1.2 7 0 Increased creatinine 15 0.7 31 0.7 Hypomagnesemia 15 0 25 1.8
The laboratory monitoring parameters for patients treated with Ipilimumab (Yervoy) and Nivolumab (Opdivo) include:
- Hematology:
- Anemia
- Lymphopenia
- Neutropenia
- Thrombocytopenia
- Chemistry:
- Hyponatremia
- Hyperglycemia
- Increased AST
- Increased ALT
- Hypocalcemia
- Increased alkaline phosphatase
- Hyperkalemia
- Hypokalemia
- Hypercalcemia
- Hypoglycemia
- Increased creatinine
- Hypomagnesemia 2
From the Research
Laboratory Monitoring Parameters
The laboratory monitoring parameters for patients treated with Ipilimumab (Yervoy) and Nivolumab (Opdivo) include:
- Elevated leukocyte counts 3
- Alanine aminotransferase (ALT) 3, 4, 5
- Aspartate aminotransferase (AST) 3, 4, 5
- Bilirubin 3
- Creatinine 3
- Amylase 3
- Lipase 3
- Thyroid-stimulating hormone (TSH) 3, 6
Frequency of Laboratory Monitoring
The frequency of laboratory monitoring can be reduced in asymptomatic patients with metastatic renal cell carcinoma treated with nivolumab or nivolumab+ipilimumab, as a reduced frequency of laboratory analyses would rarely miss dose delay criteria 3.
Adverse Events
Treatment-related adverse events that require laboratory monitoring include:
- Colitis 4
- Diarrhea 4
- Hypophysitis 4
- Hepatitis 5
- Thyroid dysfunction (including thyrotoxicosis and hypothyroidism) 6
Patient Outcomes
Patient outcomes, including disease control rate, objective response rate, progression-free survival, and overall survival, can be affected by the use of ipilimumab and nivolumab 4, 7.