Mechanism of Action:

• Nivolumab: An immune checkpoint inhibitor targeting the PD-1 receptor on T-cells, preventing interaction with its ligands PD-L1 and PD-L2, thus promoting T-cell activation and anti-tumor response.

• Relatlimab: Inhibits LAG-3, another immune checkpoint protein, thereby enhancing T-cell proliferation and activity through a complementary mechanism to Nivolumab.

• Combination of nivolumab (PD-1 inhibitor) and relatlimab (LAG-3 inhibitor), enhancing T-cell activation more than either agent alone.

• Efficacy: In clinical trials, Opdualag showed improved progression-free survival compared to nivolumab monotherapy (10.1 months vs 4.6 months).

Indications:

• Approved for use in metastatic or advanced melanoma, as a combination therapy for patients not previously treated with PD-1 or PD-L1 inhibitors.

• Treatment Duration:
• Continue until disease progression or unacceptable toxicity.

Dosing and Administration:

• Dosing: 480 mg nivolumab and 160 mg relatlimab intravenously every 4 weeks.

• Administer as a 30-minute intravenous infusion.

• Use a sterile, non-pyrogenic, low-protein-binding in-line filter (pore size 0.2-1.2 μm).

• Visually inspect the solution before administration. It should be clear to opalescent, colorless to slightly yellow.

• Do not co-administer other medications through the same IV line.

• Typical dosing involves both drugs administered intravenously every 4 weeks.

• Follow the latest guidelines on dosing adjustments for toxicities and renal or hepatic impairment.

• Monitor for infusion reactions during and after administration; have emergency medications and equipment ready.

Adverse Effects:

• Common: Fatigue, rash, musculoskeletal pain, diarrhea, and nausea.

• Immune-Related Adverse Events (irAEs): Can affect various organs (skin, liver, endocrine glands, gastrointestinal tract) and require close monitoring and early intervention. Treat as per the severity, usually requiring corticosteroids or immunosuppressants.

• Cardiovascular effects: Be vigilant about myocarditis and pericarditis, which, though rare, have been reported.

Monitoring Parameters:

• Immune-Mediated Adverse Reactions (IMARs):
• Can affect any organ system and may be severe or fatal.
• Common IMARs include lung, intestinal, liver, hormone gland, kidney, and skin problems.
• Educate patients to report any new or worsening symptoms promptly.

• Infusion-Related Reactions:
• Can be severe; monitor patients during and after infusion.

• Monitoring: Assess creatinine, liver enzymes, and thyroid function at baseline and throughout treatment.

• Monitor for signs of colitis, hepatitis, endocrinopathies (e.g., hypothyroidism, adrenal insufficiency), and pneumonitis.

Combination Therapy Synergy:

• Harnesses dual checkpoint inhibition, which can provide enhanced anti-tumor activity compared to monotherapy with checkpoint inhibitors.

• It's essential to evaluate the patient's overall health and potential benefit-risk ratio before initiating therapy.

Patient Education:

• Explain the purpose of the dual therapy and its working mechanism in layman's terms to alleviate patient anxieties.

• Discuss potential side effects and the importance of reporting any new or worsening symptoms immediately.

Managing Side Effects:

• Educate patients to recognize signs of serious side effects, such as severe diarrhea, yellowing of the skin or eyes (jaundice), shortness of breath, and significant fatigue.

• Encourage adequate hydration and nutrition, and advise on dietary adjustments in case of gastrointestinal side effects.

• Discuss the need for regular laboratory tests and appointments for monitoring.

Follow-Up Care:

• Schedule and remind patients of their regular follow-up visits for blood work and clinical evaluation.

• Coordinate with a multidisciplinary team to manage and promptly address side effects.

Emotional Support:

• Provide emotional and psychological support, as the treatment journey can be challenging. Encourage involvement in support groups or counseling services if available.

Documentation:

• Document all findings, patient interactions, and any side effects meticulously to ensure continuity of care and facilitate effective communication among the healthcare team.

Conclusion: