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Relatlimab LAG-3 — SCE Medical Oncology MCQ

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HardMelanoma & SkinRelatlimab LAG-3SCE Medical Oncology

A 60-year-old man with metastatic melanoma starts nivolumab + relatlimab (anti-LAG-3). What is the rationale for adding LAG-3 inhibition to PD-1 blockade?

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Correct answer: E — LAG-3 is a distinct immune checkpoint receptor co-expressed with PD-1 on exhausted T-cells; dual blockade of both checkpoints provides synergistic immune activation with a more favourable toxicity profile than nivolumab + ipilimumab (anti-CTLA-4)

LAG-3 (lymphocyte-activation gene 3) is an inhibitory receptor co-expressed with PD-1 on exhausted tumour-infiltrating T-cells. The RELATIVITY-047 trial showed nivolumab + relatlimab improved PFS over nivolumab alone (10.1 vs 4.6 months) in first-line melanoma, with a more manageable toxicity profile than nivolumab + ipilimumab (~19% grade 3-4 vs ~59%). The 3-year OS data showed a clinically meaningful but not statistically significant OS improvement. This represents the first approved anti-LAG-3 therapy and the second dual ICI combination after nivolumab + ipilimumab.

Reference: RELATIVITY-047 Tawbi et al NEJM 2022; 3-year update Tawbi et al JCO 2025; ESMO 2024 Melanoma