Exploring the Frequency and Risk Factors of Hyperprogressive Disease in Patients with Advanced Melanoma Treated with Immune Checkpoint Inhibitors

Hyperprogressive disease (HPD) is described as the unexpected rapid growth of a tumour accompanied by a decline in performance status. While immune checkpoint inhibitors (ICIs) have improved outcomes in advanced melanoma, HPD remains a significant challenge in a subset of patients. Although HPD has been extensively studied in various solid tumours, research specifically focusing on advanced melanoma remains limited. We analysed 158 advanced melanoma patients, with 66.5% (<i>n</i> = 105) receiving anti-PD-1 and 33.5% (<i>n</i> = 53) receiving nivolumab plus ipilimumab. The median overall survival was 4.9 months for patients with HPD compared to 8.9 months for those with progressive disease without HPD (<i>p</i> = 0.014). Factors associated with HPD included liver metastasis (<i>p</i> = 0.002), three or more metastatic sites (<i>p</i> < 0.001), elevated lactate dehydrogenase levels (<i>p</i> = 0.004), and Eastern cooperative oncology group performance status ≥2 (<i>p</i> = 0.023). Multivariate analysis identified the Royal Marsden Hospital score (HR 3.675, 95% CI: 1.166-11.580, <i>p</i> = 0.026) as an independent risk factor for HPD, with the MDA-ICI score also trending towards significance (HR 4.466, 95% CI: 0.947-21.061, <i>p</i> = 0.059). This study provides valuable insights into the frequency and factors associated with HPD in advanced melanoma patients treated with ICIs, highlighting the relevance of clinical markers and scoring systems in predicting HPD risk.