Czech Registry of Monoclonal Gammopathies - Technical Solution, Data Collection and Visualisation.

Monoclonal gammopathies of undetermined significance

Clonotype-Naïve Detection of Clonality in Patients Suspected of Having Multiple Myeloma or Monoclonal Gammopathy Using Peripheral Blood Cell-Free RNA (cfRNA)

Ixazomib Plus Lenalidomide-Dexamethasone (IRd) in Relapsed/Refractory Multiple Myeloma (MM) Patients (Pts) - Effectiveness in Routine Clinical Practice Is Similar to the Efficacy in the Phase 3 Tourmaline-MM1 Trial: A Pooled Analysis from the Insight MM Observational Study and the Czech Registry of Monoclonal Gammopathies (RMG)

Dear Editor, Renal diseases associated with monoclonal gammopathy without symptomatic multiple myeloma (MM), Waldenstrom’s macroglobulinemia (WM), or chronic lymphocytic leukemia (CLL) are increasingly known.[1] Many of these patients have a small clonal population of plasma cells (PCs) or B cells. The International Kidney and Monoclonal Gammopathy Research group (IKMG) introduced the term monoclonal gammopathy of renal significance (MGRS) in 2012.[1] The MGRS includes monoclonal gammopathy of uncertain significance (MGUS), smoldering MM, smoldering WM, monoclonal B-cell lymphocytosis (MBL), CLL, and low-grade B-NHL associated with renal involvement.[1,2] The diagnosis of MGRS is based on renal biopsy and monoclonal protein identification. B-cell or PC clone identification is paramount for a clone-directed therapy for long-term hematologic response.[2] As these clones are small, a highly sensitive technique like flow cytometry (FCM) should be used to identify clonality.[3] It is important to identify MGRS as these patients do not respond well to immunosuppressive therapy, have a high rate of recurrence post renal transplantation, and can progress to corresponding hematological malignancy.[4] We are describing two cases of MGRS where we could confirm the presence of a small clonal PC population using FCM. The case characteristics are listed in Table 1.Table 1: Clinical characteristics of the two cases of MGRSFCM for PCs was performed on the bone marrow (BM) sample collected in ethylenediaminetetraacetic acid (EDTA). The sample was lysed and staining done using a panel of antibodies against CD38-APC-Cy7, CD138-PE, CD45-PerCP-Cy5.5, CD19-PE-Cy7, CD27-FITC, CD81-FITC, CD56-APC, CD117-APC, intracellular anti-kappa-APC, and anti-lambda-FITC. Specimens were acquired using three-laser BD FACS Canto-II (BD Biosciences, San Jose, CA, USA) and analyzed on BD FACS Diva software version 8.0.1. Case 1 showed 0.2% PCs on CD38, CD138, CD45, and side scatter (SSC) gating. Of these, half, that is, 0.1% PCs, showed an abnormal immunophenotype (CD56+/CD19−/CD81−/CD45) with a κ-restriction [Figure 1]. Case 2 showed 0.9% PCs on CD38, CD138, CD45, and SSC gating, including 0.8% λ-clonal PCs with an abnormal immunophenotype (CD56+/CD19−/CD27−/CD45 partial loss).Figure 1: Plasma cell immunophenotyping in case 1: plasma cell gating on CD38/CD138 (plot 1), plasma cell gate refinement on CD38/CD45 (plot 2), abnormal PCs (blue), normal PCs (orange), and mature lymphocytes (green) on CD19/CD45 (plot 3), CD56 expression with CD81 loss in abnormal PCs, while the normal PCs express CD81 and are negative for CD56 (plot 4), κ-restricted abnormal PCs and polyclonal B cells (purple) (plot 5), polyclonal normal PCs (orange) and B cells (purple) (plot 6). PC = plasma cellIn both cases, clonality in BM could be proven on FCM, whereas immunohistochemistry showed a polyclonal population. Clonal identification is important as same renal lesions can be found in different hematological disorders and treatment varies depending upon the type of clone (B cell/PC).[2] Immunohistochemistry could be useful only when a major PC clone is present and polyclonal population is lacking.[2] However, immunohistochemistry has low sensitivity when less number of abnormal PCs are admixed with polyclonal population.[3] FCM has the advantage of studying a large number of cells and simultaneous measurement of multiple antigenic expressions. Sensitive FCM can detect monoclonal PCs at a sensitivity of 10 − 4–10 − 6 and can discriminate between MGUS and MM. The number of residual polyclonal PCs is a useful discriminating marker between MGUS and MM.[5] MGUS usually has more than 5% normal plasma cells (NPCs) within total BM PCs (both our cases showed NPCs of 50% and 20%, respectively).[5] To conclude, characterization and clonality identification of PCs or B cells in BM by FCM is a must in cases of MGRS as it is highly sensitive and guides in appropriate decision-making to guide correct therapy. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

P-075: Myeloid derived suppressor cells are not elevated in monoclonal gammopathies

Activation of MYC Pathway Is a Unifying Pathological Event in the Progression from Monoclonal Gammopathy of Undetermined Significance (MGUS) to Myeloma (MM).

Light-chain MGUS defined as per the revised definition of the istopmm study: Experience from the university of calgary MGUS clinic

Correlation of Cytomorphology, Immunophenotyping, and Interphase Fluorescence in Situ Hybridization (FISH) in 381 Patients with MGUS and 310 Patients with Multiple Myeloma.

N-Terminal Fragment of the Type-B Natriuretic Peptide (NT-proBNP) Is an Independent Prognostic Factor for Overall Survival in Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS)

Patterns of Venous Thromboembolism (VTE) Following Monoclonal Gammopathy of Undetermined Significance (MGUS) and Multiple Myeloma (MM) among 4 Million U.S. Veterans.

P-035: AI-based models for the identification of critical genetic biomarkers to distinguish MM from MGUS using the WES data

Short-Term Risk of Progression of Patients with Asymptomatic Monoclonal Gammopathies to Active Multiple Myeloma: The Critical Impact of the Tumoral Mass

Body Mass Index and Clinical Factors Associated with Monoclonal Gammopathy of Undetermined Significance (MGUS) Progression in Olmsted County, Minnesota

MYD88 L265P in Waldenström macroglobulinemia, immunoglobulin M monoclonal gammopathy, and other B-cell lymphoproliferative disorders using conventional and quantitative allele-specific polymerase chain reaction

Serum Proteomic Profiling to Identify Biomarkers of Progression from Monoclonal Gammopathy of Unknown Significance (MGUS) to Multiple Myeloma (MM) Among African Americans and Whites