Macrophage reprogramming, not CD8 T cell dynamics, underlies response to PD-1 blockade in high-risk smoldering multiple myeloma

Processed datasets supporting the NivoRd manuscript (ClinicalTrials.gov NCT02903381). Eight patients with high-risk smoldering multiple myeloma received nivolumab combined with lenalidomide and low-dose dexamethasone; paired pre- and post-treatment bone marrow biopsies were profiled by imaging mass cytometry (IMC) and single-cell RNA sequencing (scRNA-seq). Key finding: response to PD-1 blockade in HR-SMM correlates with macrophage reprogramming rather than with any change in the CD8 T cell compartment. Responders acquired an IFN-γ–polarized, PD-L1-low macrophage state; non-responders retained TNFα/NF-κB–dominant, PD-L1-high macrophages. Contents of this version: CD138neg_immune_cells.h5ad — scRNA-seq AnnData for 90,849 CD138− bone marrow immune cells across 12 cell types (R n=3, NR n=2). CD138pos_tumor_cells.h5ad — scRNA-seq AnnData for 23,362 CD138+ plasma cells. IMC-import.h5ad — IMC AnnData after image import (input to the IMC analysis pipeline). posttreatment_macrophage_DGE_results.csv, pretreatment_macrophage_DGE_results.csv — macrophage differential expression (per-cell linear mixed model with patient random intercept). master_gsea_results.csv — Hallmark GSEA outputs across cell types and timepoints. gene_expression_summary.csv, cytogenetic_validation.csv — CD138+ plasma-cell gene-expression and cytogenetic validation. differential_plasma_macrophage_pretreatment.csv, differential_cd4_macrophage_pretreatment.csv — LIANA ligand-receptor inference (pre-treatment, exploratory). Code: scripts to reproduce all figures are at GhobrialLab/NivoRd_trial_2026. Forthcoming (next version): IMC analysis CSVs (phenotyped-obs.csv, pheno_8clus-cells_data.csv, pheno_8clus-sample_pct.csv, combat_all_markers.csv, nivo_clinical.csv, nivo_md.csv, nivo_MSPike.csv) consumed by IMC/IMC_figures.Rmd.