What is the role of Lymphocyte-Activated Gene 3 (LAG3) as a marker in treating metastatic melanoma?

From the Research

LAG-3 as a Marker in Treating Metastatic Melanoma

• LAG-3 is an immune checkpoint receptor that negatively regulates T-cell function and facilitates immune escape of tumors 1, 2, 3, 4, 5.
• The expression of LAG-3 has been observed in 81% of metastatic melanoma patients, with staining in tumor-infiltrating lymphocytes (TILs) and dendritic cells 1.
• Patients with higher proportions of LAG-3+ cells tend to have better clinical outcomes, including longer progression-free survival (PFS) 1, 2.
• LAG-3 expression positively correlates with TIL score, suggesting its potential role as a predictive marker of response and survival in metastatic melanoma 1.
• The combination of anti-LAG-3 and anti-PD-1 therapies has been shown to improve PFS in metastatic melanoma patients compared to anti-PD-1 therapy alone 1, 4.

Clinical Relevance of LAG-3 Expression

• LAG-3 expression has been associated with clinical progression of melanoma, with high expression levels tend to have a shorter PFS 2.
• The assessment of LAG-3 expression via immunohistochemistry (IHC) may be a useful tool in determining its role as a predictive marker of response and survival in metastatic melanoma 1.
• Further studies are needed to fully understand the biology of LAG-3 and its potential as a target for cancer therapy 3, 5.

Combination Therapies with LAG-3 Inhibitors

• The combination of relatlimab (anti-LAG-3) and nivolumab (anti-PD-1) has been approved for treating unresectable or metastatic melanoma 3, 4.
• Clinical trials are ongoing to evaluate the efficacy and safety of anti-LAG-3 in combination with anti-PD-1 across multiple tumor types and settings 4.