Fig. 1: Smoldering patients with early progression have more differentiated T cell profiles.

A Peripheral blood (PB) was collected from smoldering multiple myeloma (SMM) patients with PB mononuclear cells (PBMCs) being used for high-dimensional spectral cytometry-based T cell characterization using algorithm-assisted cell clustering and PB plasma being used for immunoproteomic analysis with Olink. B SMM patients were divided into early progressors (n = 9, median PFS 2.1 years) and non-progressors (n = 9, median follow-up 8.6 years). C–E Dimensionality reduction analysis and algorithm-assisted cell clustering identified that early progressors had enrichment for CD8⁺CD45RA⁺CCR7^-CD62L^- T cells with high relative expression of CD57 and TOX (CD8 T_EX) and CD4⁺CD45RA⁺CCR7^-CD62L^- T cells with high relative expression of CD57 (CD4 T_EX). F PB plasma from SMM patients with early progression showed ~2-fold higher concentrations of IL-18, MMP-1, CDCP1, soluble PD-L1, and TNF. G Spectral cytometry data was additionally used for random forest (RF) modeling H A table showing model performance for the non-progressors versus non-progressors cells is shown. The model’s overall accuracy after five-fold cross-validation was 0.75. I A feature importance plot from RF modeling shows that Granzyme B, CD272, Granzyme K, and CD45RA expression values most heavily contribute to outcome predictions using the RF method. J SHAP analysis of the top four features shows that high expression values of all four proteins are associated with progression. In this figure, each dot represents a cell from a subset of the testing cohort.