Predictive Factors in Metastatic Melanoma Treated with Immune Checkpoint Inhibitors: From Clinical Practice to Future Perspective

Simple Summary Metastatic melanoma treatment has greatly changed in the last decade due to the introduction of target therapies and immune checkpoint inhibitors. The combination of immune checkpoint inhibitors led to an unprecedented median overall survival of 72 months, but still, an important portion of patients did not significantly benefit from this approach. In this scenario, the identification of predictive factors is mandatory to improve treatment choices in daily practice. In this review, we summarize the most updated data on trials evaluating predictive factors in metastatic melanoma patients treated with immune checkpoint inhibitors, providing information to support daily practice decisions, and at the same time, highlighting the most promising future perspectives.Abstract The introduction of immunotherapy revolutionized the treatment landscape in metastatic melanoma. Despite the impressive results associated with immune checkpoint inhibitors (ICIs), only a portion of patients obtain a response to this treatment. In this scenario, the research of predictive factors is fundamental to identify patients who may have a response and to exclude patients with a low possibility to respond. These factors can be host-associated, immune system activation-related, and tumor-related. Patient-related factors can vary from data obtained by medical history (performance status, age, sex, body mass index, concomitant medications, and comorbidities) to analysis of the gut microbiome from fecal samples. Tumor-related factors can reflect tumor burden (metastatic sites, lactate dehydrogenase, C-reactive protein, and circulating tumor DNA) or can derive from the analysis of tumor samples (driver mutations, tumor-infiltrating lymphocytes, and myeloid cells). Biomarkers evaluating the immune system activation, such as IFN-gamma gene expression profile and analysis of circulating immune cell subsets, have emerged in recent years as significantly correlated with response to ICIs. In this manuscript, we critically reviewed the most updated literature data on the landscape of predictive factors in metastatic melanoma treated with ICIs. We focus on the principal limits and potentiality of different methods, shedding light on the more promising biomarkers.