Avelumab for metastatic Merkel cell carcinoma: biomarker analyses of the JAVELIN Merkel 200 trial

Avelumab (anti-PD-L1) became the first approved treatment for metastatic Merkel cell carcinoma (mMCC) based on results from the phase II JAVELIN Merkel 200 trial. Patients with mMCC with or without prior first-line chemotherapy received avelumab. Exploratory biomarker analyses from the trial found that tumors positive for Merkel cell polyomavirus (MCPyV) were characterized by an absence of driver mutations and a low tumor mutational burden. MCPyV positive tumors had increased levels of immunosuppressive M2 macrophages in the tumor environment, which seemed to correlate with PD-L1 expression; high CD8⁺ T-cell density in this tumors did not predict response to avelumab. Conversely, in patients with MCPyV negative tumors, higher CD8⁺ T-cell density seemed to be associated with response to avelumab. Compared with tumors sampled before chemotherapy, tumors sampled after chemotherapy had downregulated gene signatures for immune responses, including reduced expression of IFNγ-related pathways. Levels of activated dendritic cells in responding patients were higher in patients assessed after versus before chemotherapy. The authors conclude that these analyses provide insights into mMCC biology and potential associations with response to avelumab. Chemotherapy seems to negatively modulate the immune environment.