NIVOLUMAB/ RELATLIMAB-RMBW INJ,SOLN

Clinical Criteria Summary

Autoimmune disease
Immunosuppression including corticosteroid equivalent to >10 mg per day of prednisone
Primary immunodeficiency
History of allogeneic hematopoietic stem cell or solid organ transplant
Pregnancy (i.e. known pregnancy or positive pregnancy test)
Breastfeeding

Untreated unresectable or metastatic melanoma
Patient is not expected to tolerate treatment with nivolumab and ipilimumab, the preferred first-line immunotherapy combination due to comorbidities or performance status (see Metastatic Cutaneous Melanoma Drug Sequencing Document in Clinical Recommendations)
Consider ipilimumab 1mg/nivolumab 3mg dosing if patient unlikely to tolerate ipilimumab 3mg/nivolumab 1 mg

Care provided by a VA/VA Community Care oncology or hematology provider
Goals of care and role of Palliative Care consult have been discussed and documented
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for at least 5 months after stopping treatment

• Requirement of >10 mg/day prednisone equivalent for 2 weeks prior to study treatment administration
• Prior immune checkpoint inhibitor therapy (unless given as adjuvant or neoadjuvant therapy for melanoma)
• Radiotherapy within 2 weeks
• Active brain or leptomeningeal metastases
• Active, known, or suspected autoimmune disease
• History of myocarditis
• Pregnant or breastfeeding

• Dosage form: Single-dose vial containing 240 mg nivolumab and 80 mg relatlimab per 20 mL (12 mg/mL and 4 mg/mL)
• Regimen: 480 mg IV nivolumab and 160 mg IV relatlimab every 4 weeks
• Administration: Infused over 30 minutes with a 0.2-1.2 micrometer in-line filter
• Treatment continued until disease progression, intolerable toxicity, death, or withdrawal of consent

• Immune-mediated adverse reactions: dermatitis, immune-mediated rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, endocrinopathies, gastrointestinal toxicity, hepatotoxicity, infusion-related reactions, nephrotoxicity, ocular toxicity, pulmonary toxicity
• Cardiotoxicity: immune-mediated myocarditis, pericarditis, and vasculitis
• Disease-related concerns: transplant-related complications (graft vs. host disease, hepatic veno-occlusive disease) in patients receiving allogeneic hematopoietic stem cell transplant before or after treatment; worsening or precipitation of myasthenia gravis
• Dosage form specific: Polysorbate 80 may induce hypersensitivity reactions
• Common adverse reactions (>10%): pruritus, fatigue, rash, arthralgia, hypothyroidism, diarrhea, vitiligo
• Serious adverse events/toxicity leading to discontinuation noted (Grade 3-4 toxicity: 10.3%; Deaths: 0.8%; Toxicity leading to discontinuation: 8.5%)

• NCCN-preferred category 2A recommendation for first-line treatment of metastatic or unresectable melanoma
• Considered an alternative option for first-line combination immunotherapy if patient is eligible per VHA guidance on drug sequencing
• Standard of care includes immunotherapy, targeted therapy against BRAF V600-activating mutations, combination therapy, or single-agent immunotherapy