Navigating the landscape of immune checkpoint inhibitors and novel immunotherapies in melanoma: long-term outcomes, progress, and challenges.

Introduction: Melanoma has become the poster child for transformative outcomes in advanced malignancy from the use of immunotherapy over the last 10-15 years with median survival improving from ~ 1 to > 5 years. With the increasing repertoire of immune checkpoint inhibitors (ICI) and other novel immunotherapeutic approaches, integrating and sequencing treatments to create new paradigms has gained prominence, with focus on optimizing toxicity management and complex scenarios such as immunotherapy resistance, brain metastases, fertility, and duration of follow-up.

Areas covered: In this review, we summarize the progress and emerging evidence in melanoma treatments to date and consider management and possible future directions to improve outcomes for above-mentioned specific patient cohorts.

Expert opinion: Personalized care with integration of novel prognostic and predictive biomarkers is the way forward in tailoring not only patient selection and choice of therapy, but also duration of treatment and surveillance to allow for early recurrence detection and access to newer therapies such as tumor infiltrating lymphocytes (TIL) to maximize the curative fraction of melanoma patients. Further research is needed in optimizing ICI and other immunotherapy toxicity management, including reducing steroid exposure for better patient outcomes and preserving quality of life.