High-risk multiple myeloma predicted by circulating plasma cells and its genetic characteristics

Abstract

IntroductionCirculating plasma cells (CPC) have been reported to be one of the indicators of high-risk multiple myeloma (MM), yet the prognostic significance of CPC in Chinese population and the genetic mechanisms underlying CPC formation have not been fully elucidated.MethodsPatients with newly diagnosed MM were included in this study. We used multi-parameter flow cytometry (MFC) for CPC quantification and next-generation sequencing (NGS) technology for mutational landscape mapping to identify the correlation of CPC level with clinical characteristics and the mutations.ResultsA total of 301 patients were enrolled in this investigation. We demonstrated that CPC quantification could effectively mirror the tumor load, and CPC ≥ 0.105% at diagnosis or detectable CPC after therapy indicates poor treatment response and adverse outcome, and the introduction of CPC into the R-ISS enables a more accurate risk stratification. Interestingly, we noticed an elevated percentage of light-chain MM in patients with higher CPC. Mutational landscape revealed that patients harboring mutations in TP53, BRAF, DNMT3A, TENT5C, and IL-6/JAK/STAT3 pathway-related genes tended to have higher CPC levels. Gene enrichment analysis demonstrated that pathways involving chromosome regulation and adhesion may be potential mechanisms accounting for CPC formation.DiscussionAccordingly, quantification of CPC may provide a less-invasive and reliable approach for identifying high-risk MM in Chinese population.

Definers and drivers of functional high-risk multiple myeloma: insights from genomic, transcriptomic, and immune profiling

“…However, this test is not routinely available outside of select US institutions. Given the increasing sensitivity of peripheral blood flow cytometry assays, multiple groups have also demonstrated that circulating plasma cells are a predictor of early relapse whether detected at diagnosis or during stem cell collection ( 37 , 114 – 116 ). Advanced imaging modalities such as whole-body diffusion-weighted magnetic resonance imaging may play a role in FHRMM prognostication as well, given that persistence of focal lesions after induction may be indicative of a worsened prognosis ( 117 , 118 ).…”

“…However, this test is not routinely available outside of select US institutions. Given the increasing of peripheral blood flow cytometry assays, multiple groups have also demonstrated that circulating plasma cells are a predictor of early relapse whether detected at diagnosis or during stem cell collection (37,(114)(115)(116).…”