Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma
RCT (n=715) found inhibition of 2 immune checkpoints, LAG-3 & PD-1,with relatlimab, a LAG-3–blocking antibody (BA) in combination with nivolumab, a PD-1–BA, linked to better progression-free survival than nivolumab alone (10.1 vs. 4.6 months; HR 0.75;95% CI, 0.62-0.92, p=0.006).
Source:
New England Journal of Medicine
SPS commentary:
Progression-free survival at 12 months was 47.7% with relatlimab–nivolumab as compared with 36.0% with nivolumab.
An editorial notes the current standard of care for patients with previously untreated metastatic or inoperable melanoma is a combination of nivolumab and ipilimumab. As the data from this trial mature, it suggests that if the survival benefit of relatlimab–nivolumab is shown to be similar to or better than that of nivolumab–ipilimumab, this finding would reinforce the relatlimab–nivolumab regimen as the new standard of care for previously untreated patients with advanced melanoma. It adds that it is unlikely there will be a head-to-head trial between the two combinations, since the difference in toxic effects is stark. It speculates that perhaps patients with low LAG-3 expression would derive more benefit from receiving anti–PD-1 and anti–CTLA-4 as first-line therapy, followed by anti–LAG-3 as second-line therapy. It also highlights the importance of assessing whether relatlimab is useful in the salvage setting if primary immune checkpoint therapy fails and whether it is useful in combination with or after targeted therapy aimed at BRAF and MEK. It concludes that this trial provides evidence to support adding relatlimab to the immunotherapeutic arsenal, which will create more options in the treatment landscape for advanced melanoma.