Introduction
Opdivo (nivolumab) is a programmed death receptor-1 (PD-1) blocking antibody developed by Bristol Myers Squibb. It represents a breakthrough in cancer immunotherapy, belonging to the class of immune checkpoint inhibitors. First approved by the FDA in 2014, Opdivo has revolutionized the treatment landscape for multiple malignancies by harnessing the body's immune system to fight cancer cells.
Mechanism of Action
Nivolumab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the PD-1 receptor on T-cells, blocking its interaction with programmed death-ligand 1 (PD-L1) and PD-L2. This interaction prevents the immune suppression signal that cancer cells exploit to evade immune surveillance. By inhibiting PD-1, nivolumab enhances T-cell activation and proliferation, enabling the immune system to recognize and attack tumor cells.
Indications
FDA-approved indications for nivolumab include:
- Unresectable or metastatic melanoma
- Metastatic non-small cell lung cancer (NSCLC)
- Advanced renal cell carcinoma
- Classical Hodgkin lymphoma
- Recurrent or metastatic squamous cell carcinoma of the head and neck
- Urothelial carcinoma
- Colorectal cancer with mismatch repair deficiency
- Hepatocellular carcinoma
- Esophageal squamous cell carcinoma
- Gastric, gastroesophageal junction, and esophageal adenocarcinoma
- Malignant pleural mesothelioma
- Adjuvant treatment of melanoma, urothelial carcinoma, and esophageal/gastroesophageal junction cancer
Dosage and Administration
Standard dosing: 240 mg every 2 weeks or 480 mg every 4 weeks via intravenous infusion over 30 minutes Special populations:- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No dosage adjustment necessary
- Elderly patients: No dosage adjustment necessary
- Pediatric patients: 3 mg/kg every 2 weeks (for approved indications)
Dosing may vary based on specific indications and combination therapies. Premedication with antihistamines and/or acetaminophen may be considered for infusion-related reactions.
Pharmacokinetics
- Absorption: Administered intravenously, resulting in complete bioavailability
- Distribution: Steady-state volume of distribution is approximately 8.0 L
- Metabolism: Cleared via proteolytic degradation, similar to endogenous IgG
- Elimination: Terminal half-life is approximately 25 days
- Clearance: Linear clearance at doses ≥1 mg/kg
Contraindications
- History of severe hypersensitivity to nivolumab or any component of the formulation
- No other absolute contraindications exist, but careful risk-benefit assessment is required in patients with active autoimmune diseases or organ transplantation
Warnings and Precautions
Immune-mediated adverse reactions: May include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, and other immune-related events- Infusion-related reactions: Monitor during and after infusion
- Embryo-fetal toxicity: Can cause fetal harm
- Complications of allogeneic HSCT: Increased risk of graft-versus-host disease and steroid-requiring febrile syndrome
- Solid organ transplant rejection: Reported in patients receiving checkpoint inhibitors
Drug Interactions
- No formal drug interaction studies conducted
- Theoretical increased risk of immune-mediated adverse reactions when combined with other immunomodulatory agents
- Avoid concurrent use with live vaccines during treatment
- Caution with corticosteroids and other immunosuppressive agents that may reduce efficacy
Adverse Effects
Most common (≥20%): Fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea Serious adverse reactions:- Immune-mediated pneumonitis (3.1%)
- Immune-mediated colitis (2.9%)
- Immune-mediated hepatitis (1.8%)
- Immune-mediated endocrinopathies (thyroid disorders, hypophysitis, type 1 diabetes)
- Immune-mediated nephritis and renal dysfunction
- Infusion-related reactions (1.5%)
Monitoring Parameters
Baseline:- Complete blood count, comprehensive metabolic panel
- Thyroid function tests
- Cortisol levels
- Imaging studies appropriate for malignancy
- Regular assessment for immune-mediated adverse reactions
- Liver function tests (every 3-6 weeks)
- Renal function monitoring
- Respiratory symptoms assessment
- Dermatologic examination
- Endocrine function monitoring
Patient Education
- Report any new or worsening symptoms immediately, including respiratory difficulties, diarrhea, abdominal pain, rash, fatigue, or endocrine symptoms
- Understand the potential for delayed immune-related adverse events
- Avoid live vaccines during treatment and consult healthcare provider before vaccination
- Use effective contraception during treatment and for at least 5 months after last dose
- Keep all scheduled appointments for monitoring and follow-up
- Carry patient wallet card identifying immunotherapy treatment
References
1. Bristol Myers Squibb. Opdivo (nivolumab) prescribing information. 2023 2. Topalian SL, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443-2454 3. Weber JS, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment. Lancet Oncol. 2015;16(4):375-384 4. Brahmer JR, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015;373(2):123-135 5. Postow MA, et al. Immune checkpoint blockade in cancer therapy. J Clin Oncol. 2015;33(17):1974-1982 6. NCCN Guidelines: Various malignancy-specific guidelines featuring nivolumab 7. FDA Oncology Drug Advisory Committee materials for nivolumab approvals