Opdivo
Opdivo
Generic Name
Opdivo
Mechanism
- Targets PD‑1 on T‑cells – blocks interaction with PD‑L1/PD‑L2 ligands expressed by tumor and immune cells.
- Restores T‑cell activity – releases the “brakes” on the adaptive immune response, promoting tumor cell recognition and killing.
- Induces durable antitumor immunity – generates memory T‑cells and has activity across multiple solid and hematologic malignancies.
Pharmacokinetics
| Parameter | Typical Value | Notes |
| Absorption | N/A (IV infusion) | |
| Distribution | V_d ≈ 20 L | Predominantly extracellular fluid; limited CNS penetration |
| Metabolism | Proteolytic catabolism (lysosomal, cytosolic) | Not a substrate for CYP enzymes |
| Clearance | CL ≈ 0.12 L/day (variable by tumor burden) | Linear over therapeutic range |
| Half‑life | ~25–27 days | Supports every‑2‑week dosing |
| Elimination | Mostly via catabolism to peptides/aa | No significant renal/hepatic excretion |
> *Key pharmacology terms*: PD‑1 inhibition, immune‑checkpoint blockade, antibody pharmacokinetics.
Indications
Opdivo is FDA‑approved for the following cancers (and as of 2024, some expanded indications):
• Non‑small cell lung cancer (NSCLC) – all stages; combined with platinum / pemetrexed or pemetrexed‑based chemotherapy.
• Melanoma (unresectable metastatic) – with or without interferon.
• Renal cell carcinoma (RCC) – all histologies; in combination with ipilimumab or cabozantinib.
• Hepatocellular carcinoma (HCC) – with atezolizumab + bevacizumab.
• Head & neck squamous cell carcinoma (HNSCC) – as monotherapy or combination.
• Urothelial carcinoma – metastatic disease after platinum‑based therapy.
• Colorectal cancer (MSI‑high) – metastatic, as monotherapy.
• Breast cancer – early‑stage HER2‑negative, adjuvant, pending trials.
• Cervical cancer – metastatic, after platinum.
• Lymphomas – Hodgkin and some non‑Hodgkin (clinical trials).
> *SEO words*: Opdivo oncology, nivolumab indications, PD‑1 cancer therapy.
Contraindications
- Contraindications:
- Active systemic autoimmune disease requiring systemic therapy.
- Severe hypersensitivity to nivolumab or excipients.
- Untreated or uncontrolled infections (e.g., TB).
- History of severe immune‑mediated organ toxicity (e.g., myocarditis).
- Warnings:
- Immune‑mediated adverse events: pneumonitis, colitis, hepatitis, endocrinopathies (hypothyroidism, hypophysitis), dermatologic reactions.
- Pregnancy: Category B; no adequate human data but potential teratogenic risk.
- Lactation: insufficient data, discontinue if possible.
- Combination therapy increases immune toxicity; careful monitoring recommended.
Dosing
| Indication | Dose | Schedule | IV infusion time |
| NSCLC, melanoma, RCC, HNSCC, urothelial, colorectal | 240 mg IV over 40 min or 3 mg/kg IV | Every 2 weeks | 40–60 min (depending on body weight) |
| Combination (Opdivo + ipilimumab) | 3 mg/kg IV (Opdivo) + 1 mg/kg IV (ipilimumab) | Opdivo q2 wks; ipilimumab q3 wks | 40–80 min |
• Premedication: Not routinely required, but antihistamine/acetaminophen may be given for infusion reactions.
• Concomitant medications: Avoid immune‑suppressants (unless required for organ transplantation).
• Infusion protocol: Slow in first 15‑20 min; watch for IV reactions.
Adverse Effects
Common ( *Key phrase*: immune‑mediated toxicity**.
Monitoring
- Baseline labs: CBC, CMP, LFTs, TFTs, serum creatinine.
- During treatment (every 2 weeks):
- CBC, CMP, electrolytes.
- Thyroid function (T4, TSH).
- Liver enzymes.
- Check for signs of pneumonitis (CXR or high‑resolution CT if symptomatic).
- Imaging: CT/MRI per RECIST every 6–8 weeks for disease assessment.
- Patient education: Report new symptoms—dyspnea, abdominal pain, jaundice, neurological changes.
Clinical Pearls
- Flat‑Dose vs Weight‑Based: The fixed 240 mg q2 wks is equivalent to weight‑based dosing and simplifies pharmacy preparation.
- Combination Start‑Up: Initiate with low‑dose ipilimumab if combining to reduce early colitis risk.
- Autoimmune History: Assess disease activity; consider tapering steroids to mitigate risk while maintaining cancer control.
- Pneumonitis Screening: Baseline chest X‑ray is optional; vigilant clinical review >12 weeks is essential for early detection.
- Gastroenterology Collaboration: For patients with significant colitis, coordinate with GI for diagnostic work‑up before initiating high‑dose steroids or mycophenolate.
- Rechallenge: Opdivo can be re‑started after grade 2–3 toxicity if resolved, often with pre‑medication steroids.
- COVID‑19: No evidence that nivolumab increases severity; maintain standard vaccination.
- Dosing in Renal/Hepatic Impairment: No dose adjustment needed, but monitor organ function.
- Pediatric and Geriatric: Use with caution; limited data in infants; in ≥65 yrs, monitor for frailty‑related toxicities.
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• *For in‑depth study, consult the latest NCCN guidelines, FDA labeling, and recent peer‑reviewed literature (e.g., Lancet Oncology 2023, JCO 2024). Happy learning!*