PD-L1 Expression for Tailoring Treatment in Advanced Melanoma—It Is Never That Easy—Reply

In Reply We appreciate the thoughtful comments to this Viewpoint by Karahan et al that emphasize the importance of considering additional predictive parameters when determining immunotherapy treatment strategies for patients with advanced melanoma. In patients with treatment-naive unresectable or metastatic melanoma and no central nervous system metastases, various clinical and molecular biomarkers, including programmed cell death ligand 1 (PD-L1) status (1% cut-off), liver metastases, BRAF mutational status, and the number of involved metastatic organs may help guide the shared decision-making process for dual checkpoint inhibition with ipilimumab plus nivolumab vs anti–programmed cell death 1 (PD-1) monotherapy. In addition, acknowledging the challenges in precisely defining this population in clinical trials and clinical studies, patients with rapidly progressing and/or symptomatic disease, very high tumor burden, or disease localization in organs at high risk (eg, close to critical anatomic structures like the spinal cord or upper airways) might obtain superior benefit from combination therapy with ipilimumab plus nivolumab due to the fast kinetics of response. To our knowledge, no defined biomarkers, other than PD-L1 at the 1% cut-off, exist for guiding the choice between the combination of relatlimab plus nivolumab and anti-PD-1 monotherapy.

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Dicembre 2024