Treatment of advanced melanoma with combined immune checkpoint inhibitor (ICI) therapy is complicated in up to 50% of cases by immune-related adverse events (irAE) that commonly include hepatitis, colitis and skin reactions. We previously reported that pre-therapy expansion of cytomegalovirus (CMV)-reactive CD4(+) effector memory T cells (T-EM) predicts ICI-related hepatitis in a subset of patients with Stage IV melanoma given alpha PD-1 and alpha CTLA-4. Here, we develop and validate a 10-color flow cytometry panel for reliably quantifying CD4(+) T-EM cells and other biomarkers of irAE risk in peripheral blood samples. Compared to previous methods, our new panel performs equally well in measuring CD4(+) T-EM cells (agreement = 98%) and is superior in resolving CD4(+) CD197(+) CD45RA(-) central memory T cells (T-CM) from CD4(+) CD197(+) CD45RA(+) naive T cells (T-naive). It also enables us to precisely quantify CD14(+) monocytes (CV = 6.6%). Our new "monocyte and T cell" (MoT) assay predicts immune-related hepatitis with a positive predictive value (PPV) of 83% and negative predictive value (NPV) of 80%. Our essential improvements open the possibility of sharing our predictive methods with other clinical centers. Furthermore, condensing measurements of monocyte and memory T cell subsets into a single assay simplifies our workflows and facilitates computational analyses.