Elevated non-clonal bone marrow plasma cell fraction at diagnosis is associated with improved outcomes in multiple myeloma.

In newly diagnosed multiple myeloma (NDMM), current risk stratification relies on cytogenetics and disease burden, but emerging immune parameters may refine prognosis. While a higher non-clonal plasma cell fraction (NCPF) predicts favorable outcomes in smoldering myeloma, its relevance in NDMM remains unexplored. We retrospectively analyzed 798 patients with NDMM where baseline bone marrow aspirates were tested to determine the NCPF, defined as the proportion of non-clonal plasma cells among total plasma cells. An NCPF ≥ 5% defined the NCPF-Enriched group. NCPF-High was observed in 124 patients (15.5% of all cohort). Compared to NCPF-Low, NCPF-Enriched patients had lower overall bone marrow plasma cell burden (median 20% vs. 50%, p < 0.0001), higher rates of hyperdiploidy (71% vs. 59%, p = 0.025), and similar cytogenetic risk. Six-year overall survival (OS) was significantly higher in NCPF-Enriched (70.3% vs. 56.5%, p = 0.0096), with independent prognostic value in multivariable analysis (HR 0.64, p = 0.03). Progression-free survival was also superior (HR 0.69, p = 0.006) in the NCPF-Enriched cohort in the setting of comparable treatment approaches. A higher non-clonal plasma cell fraction at diagnosis is independently associated with improved outcomes in NDMM, highlighting its potential as a novel immune prognostic biomarker warranting further investigation.