A retrospective study of ipilimumab plus nivolumab in anti–PD-L1/PD-1-refractory merkel cell carcinoma.

Abstract

9521 Background: Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma with a high recurrence and mortality rate. Immune checkpoint inhibitors (ICIs) targeting the PD-L1/PD-1 axis have shown significant clinical benefit with durable responses in patients with advanced MCC leading to regulatory approvals by the U.S. Food and Drug Administration for two agents: avelumab (anti-PD-L1) and pembrolizumab (anti-PD-1). However, many patients (̃50%) with advanced MCC treated with ICI do not experience tumor regression. Studies regarding systemic therapy options following progression due to primary or acquired resistance to immunotherapy are limited and management remains a clinical challenge. In this retrospective study, we evaluated objective clinical response to combination ipilimumab and nivolumab (ipi-nivo) salvage therapy in advanced MCC refractory to anti-PD-L1/PD-1 treatment. Methods: We reviewed the electronic medical record at Mass General Brigham associated institutions to identify patients with advanced MCC that progressed on upfront immunotherapy (e.g., pembrolizumab, avelumab or nivolumab) and were re-challenged with combination ipi-nivo between 2016 to 2021. Patients treated with prior surgery, radiation, or cytotoxic chemotherapy after progressing on immunotherapy were not excluded. Responses to ipi-nivo were evaluated for every patient at each re-staging/interval assessment following baseline analysis utilizing Response Evaluation Criteria in Solid Tumors (RECISTv1.1) as well as immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) to ensure conventional RECIST did not underestimate the benefit of ipi-nivo. Results: Four patients (31%) experienced grade III/IV immune-related adverse events. No patients (0/13) in this case series achieved an objective response via RECISTv1.1/irRECIST. Stable disease was seen in 23% (3/13) and the median progression-free survival was 1.3 months (90% CI, 1.1-1.5). The median overall survival from the initiation of ipi-nivo was 4.7 months (95% CI, 3-17). Conclusions: This study suggests limited, if any, clinical benefit of ipi-nivo in patients with advanced anti-PD-L1/anti-PD-1-refractory MCC. New strategies for second-line treatment of MCC are needed and referral to innovative clinical trials should be a priority for patients with refractory metastatic MCC.