Nivolumab

Mechanism of action

Nivolumab is a fully human, monoclonal IgG4 antibody that binds to programmed death-1 (PD-1) receptors with high specificity and affinity. PD-1 is expressed on T cells and dampens their immune response upon binding ligands PD-L1 and PD-L2 on APCs. This mechanism is pivotal to regulating central and peripheral tolerance. In cancer, aberrant PD-L1 expression by tumor cells or immune cells in the tumor microenvironment deactivates PD-1, expressing tumor-infiltrating lymphocytes, thereby allowing tumor cells to escape immune recognition and elimination. By inhibiting PD-1 function, nivolumab releases immune cells from pathological immune suppression, allowing them to recognize and counter tumor cells.

Clinical Use

Monoclonal antibody:
Treatment of advanced (unresectable or metastatic) melanoma, non-small cell lung cancer, renal cell carcinoma, classical Hodgkin lymphoma, squamous cell cancer of the head and neck and urothelial carcinoma

Side effects

The most common Immune-related adverse events (iRAEs) affect systems include the gastrointestinal and integumentary systems, usually manifesting as a pruritic rash, diarrhea, or colitis. When immune-mediated endocrine inflammation subdues, glandular function may be compromised, thus necessitating permanent hormone substitution. This includes nivolumab-induced hypothyroidism, hypopituitarism, adrenal insufficiency, and diabetes mellitus type 1.
Immune-mediated pneumonitis is a rare adverse effect associated with severe manifestations. Immune-related myocarditis is a very uncommon adverse event with high lethality. Less common adverse effects include ocular (uveitis, conjunctivitis, myositis of periocular muscles), inflammatory hepatitis, endocrinopathies such as hypothyroidism, hypopituitarism, and adrenal insufficiency. Other rare adverse events include those affecting the neurological system (encephalitis, Guillain-Barré syndrome).

Drug interactions

Potentially hazardous interactions with other drugs
Live vaccines: avoid concomitant use

Metabolism

The metabolic pathway of nivolumab has not been investigated. It is expected to be degraded into small peptides and amino acids via catabolic pathways in the same way as endogenous IgG

References

[1] Anthony V Serritella, Niraj K Shenoy. “Nivolumab Plus Ipilimumab vs Nivolumab Alone in Advanced Cancers Other Than Melanoma: A Meta-Analysis.” Jama Oncology (2023): 1441–1446.
[2] Jonathan Ho, C. Kelly, Erick A. Argueta. “S3644 Nivolumab-Induced Liver Injury.” American Journal of Gastroenterology (2021).
[3] Yang Wang. “Nivolumab combined docetaxel versus nivolumab in patients with previously treated nonsmall cell lung cancer: a phase 2 study.” Anti-Cancer Drugs (2024).