Neoadjuvant Immunotherapy with combined Ipilimumab and Nivolumab in Melanoma Patients with Primary or In‐transit Disease

: The introduction of new therapeutic agents has revolutionized the treatment of metastatic melanoma. The approval of adjuvant anti-PD-1 monotherapy with nivolumab or pembrolizumab and dabrafenib plus trametinib has recently set a new landmark in the treatment of stage III melanoma. Now, clinical trials have shown that immune checkpoint blockade can be performed in a neoadjuvant setting, an approach established as a standard therapeutic approach for other tumour entities such as breast cancer. Recent studies suggest that a pathologic response achieved by neoadjuvant immunotherapy is associated with a long-term tumour control and that short neoadjuvant application of checkpoint inhibitors may be superior to adjuvant therapy. Most recently, neoadjuvant ipilimumab plus nivolumab in stage III melanoma was reported. With two courses of dose-optimized ipilimumab (1 mg/kg) combined with nivolumab (3 mg/kg), pathological responses were observed in 77 % of patients while only 20% of patients experienced grade 3/4 adverse events. However, neoadjuvant trials employing combined immune-checkpoint blockade conducted so far excluded patients with in transit-metastases, a common finding in stage III melanoma. Here, we report 4 patients with in transit-metastases or an advanced primary tumour who have been treated with neoadjuvant ipilimumab plus nivolumab according to the OpACIN-neo scheme (Arm B). All patients achieved a radiological disease control and a pathological response. None of the patients relapsed so far.