Macro(phage) economics.

PD-1 inhibition has been all the rage in sarcoma trials of late, and a new phase 2 trial of pembrolizumab + cyclophosphamide adds to the disappointing results. Only 3 of 50 patients with a grab-bag of sarcomas exhibited any response. But there’s more to learn here. First, sarcomas in general express low levels of PD-1, and the only patient with a partial response was the only one with PD-1 expression >10% in tumor immune cells. Conversely, most sarcomas had high levels of IDO1-expressing macrophages known to confer tumor immune evasion. TBL: PD-1 inhibition alone is simply not enough for sarcoma control, but Merck would be quick to remind us to keep the big picture in mind. There’s a lot of interplays left to explore, including adjunctive inhibition of macrophages, which just may unlock the full pembro potential.


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