Among several factors under study as potential biomarkers associated with tumor responses to ICIs, the soluble form of PD-L1 (sPD-L1) has gained particular attention due to its identified role as a poor prognostic factor in several cancer types, including multiple myeloma, diffuse large B-cell lymphoma, renal cell carcinoma, and hepatocellular, lung, and gastric cancer [18]. This evidence concerns the gene SPDL1 and plasma cell myeloma.