Abstract IA11: Clinical applications of liquid biopsy in multiple myeloma

Abstract

Abstract Multiple myeloma (MM) is characterized by recurrent cytogenetic and molecular abnormalities that have the potential to profoundly impact therapeutic decisions. Conventional karyotyping and/or FISH cytogenetics studies have identified translocations and copy number abnormalities (CNAs) that predict clinical outcomes. More recently, MM whole-exome sequencing studies have uncovered recurrent mutations in genes associated with prognosis and others that are potentially actionable and/or implicated in drug resistance. These observations highlight the need for advanced genomic platforms to inform prognosis and therapeutic decisions. Currently, molecular profiling of MM is performed on bone marrow (BM) aspirates; however, the genetic information obtained from aspirates is confounded by spatial and temporal intratumor genetic heterogeneity. Genomic studies of MM have confirmed the bias introduced by single-site biopsies, demonstrating that not all mutations are shared between targeted biopsies of extramedullary sites and BM. Further, longitudinal whole-genome sequencing studies have not only uncovered tumor heterogeneity at diagnosis but also subclonal competition with a shifting dominance of tumor clones and accumulation of genetic events during progression that are particularly affected by therapeutic pressures. Thus, information acquired from a single biopsy provides a spatially and temporally limited snapshot of a tumor that likely underestimates the complexity of the tumor genomic landscape. Analysis of circulating tumor DNA (ctDNA) and in blood plasma has the potential to overcome these barriers, providing access to the genetic landscape of all cancerous lesions and allowing for noninvasive tracking of genomic evolution over time. Circulating biomarkers can provide a “liquid biopsy” alternative to tissue biopsy, providing new opportunities for treatment tailoring based on real-time monitoring from a simple blood test. Here I will discuss the current liquid biopsy technologies under evaluation for genomic characterization of multiple myeloma. I will also describe the potential clinical applications for liquid biopsies to identify patients for targeted therapies, to track genomic changes, and to follow disease burden in patients with multiple myeloma. Citation Format: Suzanne Trudel, Trevor Pugh. Clinical applications of liquid biopsy in multiple myeloma [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr IA11.