Abstract IA42: Advances in genomic characterization of multiple myeloma and its precursor states

Abstract

Abstract Multiple myeloma (MM) is an incurable malignancy of plasma cells and the second most common adult hematologic malignancy in the USA, with an annual incidence of 6.3 new cases per 100,000 individuals. MM usually progresses from asymptomatic precursor stages, known as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). MGUS can progress into MM at a rate of 1% per year, while SMM carries a higher chance of progression of approximately 10% per year. The incidence of MGUS is about 3% of the general population aged 50 years. African Americans (AA) have a 3-fold increased prevalence of MGUS and tend to have worse MM outcomes compared to Caucasians. Some patients rapidly progress from MGUS/SMM to MM, while others remain indolent with minimal progression over their lifetime due to the significant inter-patient heterogeneity. Genomic studies are increasingly delineating the complexity of MM genomic landscape. MM genomic alterations are characterized by multiple chromosomal gains or losses, structural variations, and mutations. The full suite of MM driver events is present in most cases in the SMM stage. The most common driver events in MM are copy number alterations followed by mutations and IgH translocations; however, recent whole-genome sequencing efforts identified more structural events such as MYC translocations, chromothripsis, and chrompolexy. Recently, single-cell RNA sequencing (ScRNAseq) studies provided a better understanding of both the tumor and immune cell architecture in the bone marrow niche. Tumor cells’ ScRNAseq showed that SMM patients are indistinguishable, at the molecular level, from those with active MM and highlighted an inter and intrapatient heterogeneity. Moreover, ScRNA seq of the immune microenvironment revealed that altered immune repertoire starts as early as MGUS and evolves through SMM and MM. Few studies identified potential differences in the molecular profile between AA and Caucasian patients. However, more extensive prospective studies are needed to confirm and identify possible variations among different races and ensure better representation of minorities in MM research. Citation Format: Mark Bustoros. Advances in genomic characterization of multiple myeloma and its precursor states [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA42.