P-237: Mapping Racial Disparities in Immune Cell Dysregulations and Multiple Myeloma Outcomes Using Single-Cell Profiling

Introduction: Multiple Myeloma (MM) is one of the most common malignancies and is disproportionally diagnosed in Black populations relative to white or European. This increased incidence is associated with variations in frequencies of certain cytogenetic events, and age of onset. We propose that differences in MM incidence and outcomes in Black patients may be influenced by immune bone marrow microenvironment (BME) dysregulations, which we explored using single-cell RNA sequencing data from the MMRF Immune Atlas.

Methods: We analyzed scRNA-seq data from the MMRF Immune Atlas, a sub-cohort of the MMRF CoMMpass study. The data yielded 106 manually annotated cell populations, spanning myeloid, lymphoid, and erythroid lineages. Associations of the immune population with self-identified race were assessed using univariate and multivariate models and differential expressions, adjusting for patient sex, age, and ISS stage.

Results: Of the 263 NDMM patients in the Immune Atlas, 46 self-identified as ‘Black’ or ‘African American’, while 205 self-identified as ‘White’. Black patients had significantly higher ISS stages at diagnosis (ISS3: 42% Black, 23% White, p< 0.05), and were less likely to receive triplet therapy (50% Black, 73% White, p< 0.05), though no significant association with race and progression-free survival was observed. Significant alterations were identified in the T, NK, and Myeloid compartments adjusting for age, sex, and ISS stage. The T cell compartment in Black patients had a significantly higher cytotoxicity signature enrichment (PRF1, FGFBP2, GNLY) (p< 0.05), and higher abundances of cytotoxic CD4⁺ and CD8⁺ cell states (p< 0.001). Treg populations were slightly enriched in white patients (p< 0.05), though no differences in Naïve populations were observed. In Black patients, NK cells showed enrichment of an adaptive NK signature (KLRC2⁺, FCER1G^-, p< 0.01), a cytotoxic CD56dim population with memory-like properties often observed in certain viral infections such as CMV. These NK cells also show enrichment of MHC-II antigen presentation pathways. Lastly, Black patients also showed significant enrichment of CD16⁺ non-classical monocytes (nCM, p< 0.05) with overexpression of FCGR3A and CX3CR1 markers.

Conclusions: Multiple significant alterations in the immune microenvironment are present in Black versus White NDMM patients. Some of these alterations in Black populations, such as adaptive NK cells, have been associated with either decreased relapse, or stronger responses to therapies such as Daratumumab and ASCT, which historically have been vastly underutilized in the US Black population, especially in the first lines of therapy. Overall, this indicates that there are some alterations in the immune microenvironment with respect to self-identified race. As the immune compartment plays a significant role in therapeutic efficacy, it's important to ensure under-represented minorities are fairly included in clinical trials to assess therapeutic responses.