Multiple myeloma (MM) is a plasma cell dyscrasia that is almost always preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Some patients rapidly progress from MGUS/SMM to overt MM while others remain indolent for many years. Disease evolution also depends on the surrounding microenvironment, which can be either permissive or inhibitory of clonal expansion. The use of liquid biopsies for cancer detection and monitoring is rapidly gaining prominence. Current methods for the detection of circulating tumor cell-free DNA (cfDNA) include low-pass genome sequencing for copy number profiling and deep targeted sequencing for detection of recurrent somatic mutations. However, the sensitivity of these methods is limited among patients with minimal disease, such as MGUS or the minimal residual disease (MRD) state, on account of low tumor burden and a highly variable genomic landscape, whereby most patients do not carry any of the recurrent alterations. I will discuss our current data on detecting cfDNA and circulating tumor cells in the peripheral blood of patients with MGUS, SMM, and overt MM as well as novel personalized, sensitive methods to detect cfDNA with deep UMI-based sequencing for potential use to detect MRD. There is an urgent need for a liquid biopsy assay that can be integrated in the clinical diagnosis of patients for more sensitive tumor detection along with better characterization of their genomic and epigenetic alterations leading to much-needed solutions for integrative staging of MM precursor and MRD patients, with potential implications for patient monitoring and treatment.
References: 1. Palumbo A, Anderson K. Multiple myeloma. NEJM 2011;364:1046-60, doi:10.1056/NEJMra1011442. 2. Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood 2009;113:5418-22, doi:10.1182/blood-2008-12-195008. 3. Landgren O et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood 2009;113:5412-7, doi:10.1182/blood-2008-12-194241. 4. Kyle RA et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. NEJM 2007;356:2582-90, doi:10.1056/NEJMoa070389. 5. Landgren O. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: biological insights and early treatment strategies. Hematology Am Soc Hematol Educ Program 2013;478-87, doi:10.1182/asheducation-2013.1.478. 6. Rajkumar SV et al. Impact of primary molecular cytogenetic abnormalities and risk of progression in smoldering multiple myeloma. Leukemia 2013;27:1738-44, doi:10.1038/leu.2013.86. 7. Manier S et al. Genomic complexity of multiple myeloma and its clinical implications. Nat Rev Clin Oncol 2016, doi:10.1038/nrclinonc.2016.122.
Citation Format: Irene M. Ghobrial. Liquid biopsies as biomarkers of disease progression 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 IA10.