When OpdualagTM (nivolumab and relatlimab-rmbw), a fixed-dose combination therapy that consists of two distinct monoclonal antibodies, received FDA approval on March 18, 2022, for the treatment of unresectable or metastatic melanoma for adult and pediatric patients 12 years of age or older, it became the first approved combination therapy that includes two distinct immunotherapy agents in a single infusion. Relatlimab-rmbw is also the first approved lymphocyte activation gene-3 (LAG-3)–blocking antibody.
Immunotherapy; immune checkpoint inhibitor
Mechanism of action
Nivolumab is a programmed cell death receptor-1 (PD-1)–blocking antibody, and relatlimab-rmbw is a LAG-3–blocking antibody. The drugs work by binding to their respective immune checkpoint receptors (PD-1 and LAG-3) on immune cells and blocking activation by cancer cell proteins, which preserves T-cell activation and proliferation and enables a patient’s body to produce a more robust immune response to identify and destroy cancer cells.
Treatment of patients aged 12 or older with unresectable or metastatic melanoma
Patients who weigh at least 40 kg should receive 480 mg of nivolumab and 160 mg of relatlimab-rmbw IV every four weeks until they experience disease progression or unacceptable toxicity. Clinical trials did not establish a recommended dose for patients who weigh less than 40 kg.
The fixed dose combination of two drugs is supplied in a single infusion. Administer as an IV infusion over 30 minutes using a filter with a 0.2–1.2 micrometer pore size. Flush the line after the infusion. Do not administer other drugs through the same line.
More than 20% of patients in the combination therapy’s clinical trials reported experiencing musculoskeletal pain, fatigue, rash, pruritus, and diarrhea. The most common lab test abnormalities in more than 20% of patients in the clinical trials were decreased hemoglobin, lymphocytes, and sodium and increased AST and ALT. Rare but significant adverse reactions included severe and fatal immune-related adverse events (irAEs), infusion-related reactions, and complications following allogeneic hematopoietic stem cell transplantation.
Nivolumab and relatlimab-rmbw may cause a patient’s immune system to overreact, leading to inflammation and increased risk for adverse events that can be severe or fatal, occur in any organ system or tissue, and appear during or after treatment. Common irAEs include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatitis, and myocarditis. They often present clinically as shortness of breath, diarrhea, abnormal lab values (e.g., liver enzymes, thyroid hormones, glucose, kidney function), fatigue, headache, rash, or chest pain. Monitor patients for signs or symptoms that may signify the early development of irAEs to facilitate appropriate and prompt identification and management, including treatment interruption, high-dose steroids, or treatment discontinuation.
Teach patients to use effective contraception and avoid pregnancy and breastfeeding during their treatment and for at least five months following their last dose. Instruct them on the signs and symptoms of a reaction to report during infusions. Discuss symptoms that may indicate early presentation of irAEs and the importance of reporting them immediately to their healthcare team.
No overall differences in safety or effectiveness were observed between patients aged 65 years or older and younger patients. Because patients with preexisting autoimmune disorders or immunocompromised conditions, taking steroids or other immunosuppressive medications, or with a history of organ transplant or plans to receive a stem cell transplant using donor cells were not included in the clinical trial, they may require additional assessment and testing before or during treatment.
Unconjugated monoclonal antibodies are not classified as hazardous. Review your institution’s hazardous drug classification and safe handling procedures to ensure appropriate compliance with your local policy.
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