Association between pretreatment emotional distress and neoadjuvant immune checkpoint blockade response in melanoma
Menée à partir de données portant sur 88 patients atteints d'un mélanome de stade IIIB-D et inclus dans un essai de phase II, cette étude analyse l'association entre une détresse psychologique avant le début du traitement néoadjuvant par inhibiteurs de point de contrôle immunitaire et la réponse thérapeutique
Neoadjuvant immune checkpoint blockade (ICB) outperforms adjuvant ICB for treatment of stage IIIB–D melanoma, but potential biomarkers of response, such as interferon-gamma (IFNγ) signature and tumor mutational burden (TMB), are insufficient. Preclinical studies suggest that emotional distress (ED) can negatively affect antitumor immune responses via β-adrenergic or glucocorticoid signaling. We performed a post hoc analysis evaluating the association between pretreatment ED and clinical responses after neoadjuvant ICB treatment in patients with stage IIIB–D melanoma in the phase 2 PRADO trial (NCT02977052). The European Organisation for Research and Treatment of Cancer scale for emotional functioning was used to identify patients with ED (n = 28) versus those without (n = 60). Pretreatment ED was significantly associated with reduced major pathologic responses (46% versus 65%, adjusted odds ratio 0.20, P = 0.038) after adjusting for IFNγ signature and TMB, reduced 2-year relapse-free survival (74% versus 91%, adjusted hazard ratio 3.81, P = 0.034) and reduced 2-year distant metastasis-free survival (78% versus 95%, adjusted hazard ratio 4.33, P = 0.040) after adjusting for IFNγ signature. RNA sequencing analyses of baseline patient samples could not identify clear β-adrenergic- or glucocorticoid-driven mechanisms associated with these reduced outcomes. Pretreatment ED may be a marker associated with clinical responses after neoadjuvant ICB in melanoma and warrants further investigation. ClinicalTrials.gov registration: NCT02977052.
Nature Medicine 2023