Detection of Circulating Tumor Plasma Cells in Monoclonal Gammopathies: Methods, Pathogenic Role, and Clinical Implications

Abstract

Cancer dissemination and distant metastasis most frequently require the release of tumor cells into the blood circulation, both in solid tumors and most hematological malignancies, including plasma cell neoplasms. However, detection of blood circulating tumor cells in solid tumors and some hematological malignancies, such as the majority of mature/peripheral B-cell lymphomas and monoclonal gammopathies, has long been a challenge due to their very low frequency. In recent years, the availability of highly-sensitive and standardized methods for the detection of circulating tumor plasma cells (CTPC) in monoclonal gammopathies, e.g., next-generation flow cytometry (NGF), demonstrated the systematic presence of CTPC in blood in virtually every smoldering (SMM) and symptomatic multiple myeloma (MM) patient studied at diagnosis, and in the majority of patients with newly-diagnosed monoclonal gammopathies of undetermined significance (MGUS). These methods set the basis for further detailed characterization of CTPC vs. their bone marrow counterpart in monoclonal gammopathies, to investigate their role in the biology of the disease, and to confirm their strong impact on patient outcome when measured both at diagnosis and after initiating therapy. Here, we review the currently available techniques for the detection of CTPC, and determine their biological features, physiopathological role and clinical significance in patients diagnosed with distinct diagnostic categories of plasma cell neoplasms.

Biological Characterization and Clinical Relevance of Circulating Tumor Cells: Opening the Pandora’s Box of Multiple Myeloma

“…Herein, we summarize different studies characterizing CTCs from a phenotypic, genetic, and transcriptomic point of view in MM, as well as their clinical applicability. Many excellent reviews expanding this topic in other cancer types are available in this journal [23,24] and elsewhere [25][26][27].…”

Prognostic Value of FDG-PET/CT Parameters in Patients with Relapse/Refractory Multiple Myeloma before Anti-CD38 Based Therapy

“…Several authors have demonstrated that the presence of circulating plasma cells in peripheral blood is a prognostic biomarker that could be used for risk stratification in MM [32][33][34][35][36]. We, therefore, wanted to analyze this parameter in our series, in the context of anti-CD38 therapy.…”

Is Quantification of Measurable Clonal Plasma Cells in Stem Cell Grafts (gMRD) Clinically Meaningful?

“…The later techniques capable of greater numbers of light-chain restricted cPC quantification in the blood are as follows. Regarding a further improvement in the sensitivity and specificity of the aforementioned processes, several different conventional flow cytometry and next-generation flow cytometry (NGF) procedures and polymerase chain reaction (PCR)-based and next-generation sequencing (NGS) techniques were subsequently developed and tested in different studies ( 7 ).…”

“…Since cPCs may harbor sites outside of bone marrow or spread unevenly throughout the body, simultaneous measurement of disease activity within intramedullary and extramedullary compartments is required. Circulating plasma cells (CPCs) either at diagnosis or during mobilization can be detected in the peripheral blood among a significant number of myeloma patients (7)(8)(9)(10)(11)(12)(13). Although it can be simply a reflection of a tumor mass, it may also represent heterogeneity in the biology of the disease.…”