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BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, nivolumab and relatlimab-rmbw (Opdualag) is covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

US FOOD AND DRUG ADMINISTRATION STATUS

Nivolumab and relatlimab-rmbw (Opdualag​) was approved by the US Food and Drug Administration (FDA) on March 18, 2022, for the treatment of adult and pediatric individuals patients 12 years of age or older with unresectable or metastatic melanoma. It is administered by intravenous infusion. 

PEDIATRIC USE

The safety and effectiveness in pediatric individuals for the treatment of unresectable or metastatic melanoma​ have been established in those who weigh at least 40 kg.

​The safety and effectiveness in pediatric individuals 12 years of age or older who weigh less than 40 kg, and pediatric individuals younger than 12 years of age have not been established.

Description

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Malignant melanoma is a common skin cancer that arises from melanin cells within the upper layer of the skin or from similar cells that may be found in moles. Early-stage melanomas are mostly treatable; however, melanomas have high metastatic potential and can spread to other organs very quickly.​

Opdualag is a first-in-class immune checkpoint inhibitor that combines nivolumab (Opdivo), a programmed death-1 (PD-1)–blocking antibody, and relatlimab-rmbw​, a lymphocyte-activation gene 3 (LAG-3)–blocking antibody. Nivolumab is a human monoclonal antibody and immune checkpoint inhibitor that competes with the tumor for the PD-1 receptor on T cells and blocks the T cells' interaction with the tumor's PD-L1 and PD-L2 ligands. Consequently, the tumor is no longer able to inactivate the T cells and the antitumor response continues. Relatlimab-rmbw reduces LAG-3 pathway-mediated inhibition of the immune response and promotes T-cell proliferation and cytokine secretion. The combination of these two drugs results in increased T-cell activation compared to the activity of either antibody alone.

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PEER-REVIEWED LITERATURE

Summary

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Tawbi et al. (2022) evaluated the safety and efficacy of nivolumab and relatlimab-rmbw (Opdualag) in the phase 2/3 trial called A Study of Relatlimab Plus Nivolumab Versus Nivolumab Alone in Participants With Advanced Melanoma (RELATIVITY-047), a double-blind, randomized (1:1) trial that evaluated nivolumab and relatlimab-rmbw (Opdualag)​ versus nivolumab alone in 714 individuals 12 years of age or older with previously untreated metastatic or unresectable stage III or IV melanoma who had expression of LAG-3 and programmed death ligand-1 (PD-L1) that could be evaluated in tumor tissue​. Individuals were eligible to participate if they had received previous adjuvant or neoadjuvant therapies containing a PD-1, CTLA-4, BRAF, or MEK inhibitor (or a combination of BRAF and MEK inhibitors) if the therapy was completed at least 6 months before the date of recurrence; individuals who received previous treatment with interferon were eligible if the last dose was received at least 6 weeks before randomization.​ Participants were randomly assigned to receive nivolumab 480 mg and relatlimab 160 mg (Opdualag​) by intravenous infusion every 4 weeks (n=355) or nivolumab 480 mg by intravenous infusion every 4 weeks (n=359) until disease progression or unacceptable toxicity. The primary endpoint of the trial was progression-free survival (PFS). The results showed a statistically significant improvement in median PFS of 10.1 months in the nivolumab and relatlimab-rmbw (Opdualag)​ arm compared with 4.6 months in the nivolumab arm (HR 0.75; 95 percent confidence interval (CI), 0.62–​0.92]). The most common immune-mediated adverse events were hypothyroidism or thyroiditis (18 percent with combination vs. 13.9 percent with nivolumab), rash (9.3 percent vs. 6.7 percent), and diarrhea/colitis (6.8 percent vs. 3.1 percent). The most common grade 3 or 4 toxicities were hepatitis (3.9 percent) and adrenal insufficiency (1.4 percent) with the combination and rash (1.4 percent) and diarrhea/colitis (1.4 percent) with nivolumab, all immune-mediated. Three treatment-related deaths occurred with the combination (hemophagocytic lymphohistiocytosis​, acute pulmonary edema, and pneumonitis) and in two with nivolumab (sepsis/myocarditis and pneumonia). 

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OFF-LABEL INDICATION

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

Coding

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Policy History