Sequential immunotherapy in melanoma: is it a realistic alternative to dual immunotherapy?

The treatment of metastatic melanoma has been revolutionised with the emergence of checkpoint inhibitors. The combination of Ipilimumab and Nivolumab offers the longest overall survival but is considerably more toxic than single-agent therapy. For patients who received single-agent immunotherapy it is unclear whether second-line immunotherapy is efficacious or tolerable. This study looked at outcomes for patients treated with sequential immunotherapy and compared them to patients who received dual immunotherapy. Fifty-eight patients received both Ipilimumab and an anti-PD-1 agent during the 5-year period, twenty-seven received dual immunotherapy, twenty received first-line Ipilimumab and eleven received an anti-PD-1 agent first line. The median overall survival (OS) was 24.8 months. The 5 year survival was greatest in patients treated with dual immunotherapy (42%) compared to first-line anti-PD-1 (33.3%) and first-line Ipilimumab (0%). As second-line treatments, anti-PD-1 agents had a median OS of 16.5 months compared to Ipilimumab at 3.4 months. 77.8% of patients had grade 3/4 toxicity with dual immunotherapy compared to 10% of patients treated with first-line Ipilimumab and 0% with anti-PD-1 agents. In the second line, 72.7% of patients treated with Ipilimumab experienced grade 3/4 toxicity, compared to 20% of patients treated with second-line anti-PD-1 agents. This study suggests Ipilimumab is not efficacious in patients who progress after anti-PD-1 agents, and this sequential approach does not avoid toxicity. The emergence of new checkpoint inhibitors will hopefully provide more efficacious treatment options for patients unable to tolerate Ipilimumab.