Sex-specific plasma-immune architectural differences in bone marrow predicts overall survival in multiple myeloma
Presenter: Dharini Raghavan Session: Etiology and Molecular Epidemiology Approaches to Decipher Cancer Disparities Time: 4/21/2026 9:00:00 AM → 4/21/2026 12:00:00 PM
Authors
Dharini Raghavan 1 , Advait Madabhushi 2 , Amritpal Singh 2 , Tilak Pathak 2 , GERMAN CORREDOR 2 , Ajay K. Nooka 3 , Anant Madabhushi 2 1 Georgia Institute of Technology, Atlanta, GA, 2 Emory University, Atlanta, GA, 3 Assistant Professor, Emory University Winship Cancer Institute, Atlanta, GA
Abstract
Background: Multiple myeloma (MM) disproportionately affects men (57% vs. 43% women), yet the biological basis for these sex differences remains unexplored. The bone-marrow immune microenvironment, particularly plasma-immune spatial organisation, plays a critical role in disease progression and therapeutic response. Emerging evidence suggests that sex-specific immunologic differences contribute to disparities in cancer biology and outcomes, yet these patterns remain poorly characterised in MM. Understanding whether plasma-immune architectural features differ by sex and whether they carry prognostic value may inform more personalised risk stratification in MM. Methods: We identified 104 MM whole-slide bone-marrow biopsies from the Cancer Moonshot Biobank. Using pre-trained deep learning models, immune cells were segmented, followed by plasma cell detection. Morphological (density and spatial) patterns of plasma cells and other immune cells were quantified in peri-tumoral and non-tumoral compartments, and FDR-corrected Welch’s t-tests were performed to compare gender specific differences. Prognostic associations of these features were assessed using univariate Cox proportional hazard models. Results: On comparing the immune cell phenotypes, males exhibited higher plasma density relative to tumor density (0.158 vs female 0.105, FDR p=0.029). Spatial analysis showed that males also had higher plasma-lymphocyte cluster overlap in the peri-tumoral stroma (0.418 vs female 0.238, FDR p= 0.036). In survival analysis, overlap of plasma-lymphocyte cluster was prognostic of overall survival: HR = 1.730 (95% CI: 1.074-2.787), p= 0.018, c-index = 0.552. In contrast, there were no significant differences in density or spatial features of lymphocytes across the genders. Conclusions: Plasma cell shows gender specific differences in density and spatial arrangement, despite no significant differences in lymphocyte morphology. These sex-specific patterns appear to predict survival, supporting the need for sex-stratified risk assessment and personalised prognostication strategies in MM.
Disclosure
D. Raghavan, None.. A. Madabhushi, None.. A. Singh, None.. T. Pathak, None.. G. Corredor, None.. A. Madabhushi, None.
Cited in
Control: 8351 · Presentation Id: 3574 · Meeting 21436