Anti-PD-1 monotherapy versus anti-PD1 plus anti-CTLA4 in advanced melanoma: how do we decide?

While salvage ipilimumab can induce responses comparable to use in first-line setting for those who have failed prior anti-PD-1 therapy (9), elevated serum lactate dehydrogenase (LDH) has been shown to be an incremental and independent negative prognostic marker for therapy response rate to ipilimumab monotherapy in a retrospective analysis of 134 patients (10), where 80% of patients were treated in the second or beyond line setting. [...]to the question of optimal sequencing, a multicenter, retrospective series where 37 patients were salvaged with combination therapy following failure of anti-PD1 treatment reported a response rate of 21% and a 1-year survival rate of 55% (11), notably inferior to the reported efficacy for combination treatment (58.9% response rate, 73 and 64% 1-year and 2-year survival rates, respectively) in the first-line setting in CheckMate 067. Interestingly, the role of anti-PD-1 blockade has been evaluated in a randomized trial for the treatment of chronic hepatitis C (22), with suggestion of viral suppression efficacy for a proportion of patients. A randomized, double-blind, placebo-controlled assessment of BMS-936558, a fully human monoclonal antibody to programmed death-1 (PD-1), in patients with chronic hepatitis C viral infection.