Post-hoc analysis of the association between pretreatment emotional distress and neoadjuvant ICI blockade response in melanoma

There is a need for biomarkers of response of stage IIIB-D melanoma to neoadjuvant immune checkpoint blockade (ICB). Preclinical studies suggest that emotional distress (ED) can negatively affect antitumor immune responses via β-adrenergic or gluocorticoid signaling. Post-hoc analysis of the phase 2 PRADO trial found that among patients treated with neoadjuvant ICB for stage IIIB-D melanoma, pretreatment ED was associated with reduced major pathologic responses (aOR 0.20; p=0.038) after adjusting for IFNγ signature and tumor mutational burden and with reduced 2-year relapse-free survival (aHR 3.81; p=0.034) and reduced 2-year distant metastasis-free survival (aHR 4.33; p=0.040) after adjusting for IFNγ signature. The authors conclude that pretreatment ED may be a marker associated with clinical response after neoadjuvant ICB in melanoma.