Opdualag From Bristol Myers Squibb

Pharmacy Times, June 2022, Volume 88, Issue 6

Combination therapy with both nivolumab and relatlimab leads to increased T-cell activation compared with monotherapy with either agent alone.

The FDA has approved nivolumab and relatlimab-rmbw intravenous (IV) injection (Opdualag; Bristol Myers Squibb) to treat metastatic or unresectable melanoma in patients 12 years or older.1

The incidence of melanoma has been increasing over the past 3 decades, with an estimated 99,780 new melanoma diagnoses and 7650 melanoma-related deaths expected to occur in the United States in 2022.2

Pharmacology and Pharmacokinetics

Nivolumab is a human IgG4 monoclonal programmed death receptor-1 (PD-1) blocking antibody. It binds to the PD-1 receptor, blocks the interaction with its ligands PD-L1 and PD-L2, and reduces PD-1 pathway-mediated inhibition of the immune response. Relatlimab is a human IgG4 monoclonal lymphocyte activation gene-3 (LAG-3) blocking antibody. By binding to the LAG-3 receptor, blocking the interaction with its ligands, and reducing LAG-3 pathway-mediated inhibition of the immune response, promotion of both cytokine secretion and T-cell proliferation occurs. Combination therapy with both nivolumab and relatlimab leads to increased T-cell activation compared with monotherapy with either agent alone. The half-life of nivolumab is 26.5 days, whereas relatlimab is 26.2 days.1

Dosage and Administration

The recommended dose of Opdualag for patients 12 years or older who weigh at least 40 kg is 480 mg of nivolumab and 160 mg of relatlimab IV every 4 weeks until the disease progresses or unacceptable toxicity occurs. It should be given as a 30-minute infusion through an IV line containing a nonpyrogenic, sterile, low-protein–binding in-line nylon, polyethersulfone, or polyvinylidene fluoride filter with a pore size of 0.2 μm to 1.2 μm. Other medications should not be coadministered through the same IV line.1

Clinical Trials

The efficacy of Opdualag was evaluated in RELATIVITY-047 (NCT03470922),
a double-blind, randomized trial of 714 participants with previously untreated metastatic or unresectable stage 3 or 4 melanoma. Patients with active autoimmune disease, active or untreated brain or leptomeningeal metastases, medical conditions requiring systemic treatment with moderate- or high-dose corticosteroids or immunosuppressive medications, and uveal melanoma were excluded from the trial. Participants were randomized 1:1 to receive either nivolumab 480 mg IV every 4 weeks or Opdualag (nivolumab 480 mg and relatlimab 160 mg) IV every 4 weeks until their disease progressed or unacceptable toxicity occurred. Tumors were evaluated 12 weeks after randomization and every 8 weeks thereafter up to week 52, then every 12 weeks. The trial met its primary end point, which was progression-free survival. The median progression-free survival was 4.6 months for the nivolumab group and 10.1 months for the Opdualag group. Secondary end points were overall survival, which did not demonstrate a statically significant difference, and overall response rate.1,2

Contraindications, Warnings, and Precautions

There are no contraindications to treatment with Opdualag. Immunemediated adverse reactions (IMARs), which may be severe or fatal, can occur in any organ system or tissue and at any time after starting or discontinuing treatment with LAG-3 and PD-1/ PD-L1 blocking antibodies. Patients should be monitored for early identification and management of IMARs. Occurrence of an IMAR may warrant either discontinuing or holding of Opdualag. Creatinine, liver enzymes, and thyroid function should be assessed at baseline and throughout treatment. Opdualag can cause severe infusion-related reactions. Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation before or after being treated with a PD-1/PD-L1 blocking antibody. Because Opdualag can cause fetal harm, women of childbearing potential should use effective contraception during treatment. Opdualag should not be used during breastfeeding.

The most common adverse reactions are diarrhea, fatigue, musculoskeletal pain, pruritus, and rash. The most common laboratory abnormalities are decreased hemoglobin, lymphocytes, and sodium, increased alanine transaminase and aspartate transaminase.1,2

About The Author

Monica Holmberg, PHARMD, BCPS, is a pharmacist in Phoenix, Arizona, and Pharmacy Times® contributor.

References

1. Opdualag.Prescribinginformation.Bristol Myers Squibb; 2022. Accessed April 1, 2022. https://packageinserts.bms.com/pi/pi_opdualag.pdf

2. U.S. Food and Drug Administration approves first LAG-3-blocking antibody combination, Opdualag(nivolumab and relatlimab-rmbw), as treatment for patients with unresectable or metastatic melanoma. Bristol-Myers Squibb. News release. March 18, 2022. Accessed April 1, 2022. https://news.bms.com/news/corporate-financial/2022/U.S.-Food-and-Drug-Administration-Approves-First-LAG-3-Blocking-Antibody-Combination-Opdualag-nivolumab-and-relatlimab-rmbw-as-Treatment-for-Patients-with-Unresectable-or-Metastatic-Melanoma/default.aspx