The neverending story on the role of circulating EVs in the response and monitoring of the response to ICI in MM patients has been enriched with the investigation of possible correlation between circulating EVs in plasma of patients and the developing of acquired anti-PD1 resistance and in modulating the behaviour of both tumor and immune cells, with a direct impact on the metastatic potential of tumor cells and on the regulation of immune tolerance in cells strictly involved in the response to anti-PD1, such as T lymphocytes (T cells), dendritic cells (DCs) and macrophages. Here, PDCD1 is linked to Miyoshi myopathy.