Opdualag

Nivolumab is a monoclonal antibody that enhances the antitumor immune response by binding to the programmed death receptor-1 (PD-1) and blocking its interaction with ligand 1 and 2 (PD-L1 and PD-L2). Relatlimab is a monoclonal antibody that binds to the lymphocyte activation gene-3 (LAG-3) receptor which results in promoting T cell proliferation and cytokine secretion. The combined agents result in inhibition of tumor growth. Nivolumab;relatlimab-rmbw (Opdualag) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. The initial safety and efficacy of nivolumab;relatlimab-rmbw (Opdualag) was evaluated in a randomized trial as compared to nivolumab alone in 714 patients with previously untreated unresectable or metastatic Stage III or IV melanoma. Patients were permitted to have received prior adjuvant or neoadjuvant melanoma therapy with anti-PD-1, anti-CTLA-4, or BRAF-MEK inhibitors if received at least 6 months between the last dose of therapy and the date of recurrence. Patients with active autoimmune disease, conditions requiring corticosteroids or immunosuppressive medications, uveal melanoma, and active or untreated brain or leptomeningeal metastases were excluded. Patients received either nivolumab;relatlimab-rmbw or nivolumab every 4 weeks until disease progression or unacceptable toxicity. There were 41% of patients with PD-L1 expression greater than or equal to 1%, 75% of patients with LAG-3 expression greater than or equal to 1%, and 39% with BRAF V600 mutation-positive melanoma. The efficacy outcome measures were progression-free survival (PFS), overall survival (OS) and overall response rate (ORR). There was a significant improvement in PFS with the combination arm as compared to nivolumab alone (10.1 months vs 4.6 months,p= 0.0055). The overall survival was not significant at the time of the analysis (34.2 months vs 25.2 months) and the overall response rate was 43% for the combined group as compared to 33% with nivolumab alone. The most common adverse reactions that occurred in patients treated with nivolumab;relatlimab-rmbw included musculoskeletal pain (45%), fatigue (39%), rash (28%), pruritus (25%), and diarrhea (24%). Other clinically relevant reactions that occurred in less than 15% of patients included vitiligo, adrenal insufficiency, myocarditis, and hepatitis. The most common lab abnormalities were decreased hemoglobin (37%), decreased lymphocytes (32%), increased AST (30%), increased ALT (26%), and decreased sodium (24%). National Comprehensive Cancer Network (NCCN) Guidelines for Melanoma include recommendations for the use of nivolumab;relatlimab-rmbw for metastatic or unresectable disease. Metastatic disease includes stage III unresectable/borderline resectable disease with clinically positive node(s) or clinical satellite/intransit metastases, unresectable local satellite/in-transit recurrence, unresectable nodal recurrence, and widely disseminated distant metastatic disease. <a id="