Efficacy and safety of neoadjuvant nivolumab and ipilimumab for resectable melanoma

Abstract

Neoadjuvant immunotherapy is an emerging strategy in the management of resectable melanoma, aiming to improve long-term outcomes by inducing early immune responses before surgery. The combination of nivolumab (PD-1 inhibitors) and ipilimumab (anti–CTLA-4) has shown promise. This study’s aim is to systematically review the efficacy and safety of neoadjuvant nivolumab and ipilimumab regimens in resectable melanoma patients. A systematic search of databases was conducted following PRISMA 2020 guidelines. Studies were screened and selected based on the use of neoadjuvant nivolumab and ipilimumab combination for resectable melanoma. Risk of bias was assessed. Key outcomes included relapse-free survival (RFS), event-free survival (EFS), overall survival (OS), pathological response and grade ≥3 adverse events (AE). Seven studies comprising five randomized controlled trials (RCT), non-RCT and one retrospective cohort study with a total of 530 patients were included. The combination of neoadjuvant nivolumab and ipilimumab showed high efficacy, with RFS from 70% to 96%, EFS ≥90%, and OS ≥95% over median follow-up of 8-28 months. The most favorable outcomes were observed with low-dose ipilimumab (1 mg/kg) plus high-dose nivolumab (3 mg/kg). Pathological response rates were high, major/complete responses ≥70% of patients. However, grade ≥3 treatment-related AE were common, including rash, colitis, elevated liver enzyme. Neoadjuvant nivolumab with ipilimumab shows strong clinical and pathological response in resectable melanoma, with a potential to improve long-term outcomes. However, its use is limited by a significant risk of severe immune-related adverse events. Optimizing the dosing, lowering ipilimumab dosage, may enhance the risk-benefit profile.