Patterns of response, recurrence and progression of melanoma

Abstract

Understanding the mechanisms underlying response and resistance to immune checkpoint inhibition (ICI) is crucial for improving the treatment of melanoma. The first part of this thesis introduces the concept of neoadjuvant ICI therapy and the use of its design as platform for improving and exploring new treatment options for stage III melanoma. Updated survival data of two neoadjuvant trials with combination ICI therapy with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) and data of the PRADO trial with a response-driven personalization approach based on pathologic response are given. The second part discusses response in primary melanoma and synchronous lymph node metastases to neoadjuvant combination therapy. In addition, characteristics of patients and their tumors with recurrence after initial pathologic response to neoadjuvant combination therapy and with or without recurrence after adjuvant anti-PD-1 treatment are analyzed. The third part on stage IV melanoma examines easily accessible biomarkers for early non-responsiveness to anti-PD-1 treatment. Both the treatment of solitary progression after initial response and tumor characteristics of patients with dissociated response to ICI are described. Finally, real-world data on the efficacy and toxicity of ipilimumab plus nivolumab are presented. Insights in these diverse patterns of response, recurrence and progression, and identification of biomarkers can enable personalized treatment for patients with melanoma.