Personalized neoadjuvant immunotherapy in stage III melanoma

Abstract

Until recently, the standard of care for patients with stage III melanoma consisted of lymph node dissection followed by adjuvant immunotherapy. However, with this approach, 40–50% of patients experienced disease relapse within 3–5 years after surgery. Neoadjuvant immunotherapy is hypothesized to elicit a broader and more robust anti-tumor immune response, owing to the presence of a wider repertoire of tumor antigens.

In this thesis, results from several clinical trials investigating neoadjuvant immunotherapy in stage III melanoma are presented. The OpACIN-neo trial evaluated the efficacy, toxicity, and biomarker profiles of different dosing regimens of neoadjuvant ipilimumab combined with nivolumab. In the PRADO trial, we describe a personalized surgical and adjuvant treatment strategy guided by the pathologic response to neoadjuvant immunotherapy, which enables omission of complete lymph node dissection in patients achieving a major pathologic response. The DONIMI trial investigates various combinations of neoadjuvant immunotherapy with or without domatinostat (a histone deacetylase inhibitor), stratified by baseline IFN-γ signature.