Figure - available from: Leukemia
This content is subject to copyright. Terms and conditions apply.
The time to progression (TTP) using the IMWG progression criteria versus the qIgA progression criteria was compared The TTP was assessed by IMWG progression criteria versus the qIgA250 progression criteria (A), and qIgA500 progression criteria (B) in the newly diagnosed multiple myeloma (NDMM) testing cohort. Similarly, the TTP was assessed using the IMWG progression criteria compared to the qIgA250 progression criteria (C) and qIgA500 progression criteria (D) in the relapsed refractory clinical trial (RRMM-CT) validation cohort.
Source publication
Unlike IgG monoclonal proteins (MCPs), IgA MCP quantification is unreliable due to beta-migration of IgA MCPs on serum protein electrophoresis (SPEP). The utility of nephelometric quantitative IgA (qIgA) to monitor IgA multiple myeloma (MM) is unclear. We retrospectively studied disease response kinetics using qIgA versus MCPs by SPEP, and develope...
Citations
... The MIg typically migrates in the γ-band, but it can migrate in the β-band or α-band as well. The MIg in the α-band and β-band may be unreliable to quantify due to the co-migration of physiologic proteins such as transferrin and complement proteins 32 . The electrophoretic migration of MIg may reduce the sensitivity of SPE in detecting MG. ...
Renal involvement is common in monoclonal gammopathy (MG); however, the same patient may have both MG and non-paraprotein-associated renal damage. Accordingly, distinguishing the cause of renal damage is necessary because of the different clinical characteristics and associated treatments. In this multicenter retrospective cohort study, we described the clinicopathological characteristics and prognosis of 703 patients with MG and renal damage in central China. Patients were classified as having MG of renal significance (MGRS), MG of undetermined significance (MGUS), or hematological malignancy. 260 (36.98%), 259 (36.84%), and 184 (26.17%) had MGRS, MGUS, and hematological malignancies, respectively. Amyloidosis was the leading pattern of MGRS (74.23%), followed by thrombotic microangiopathy (8.85%) and monoclonal immunoglobulin deposition disease (8.46%). Membranous nephropathy was the leading diagnosis of MGUS (39.38%). Renal pathological findings of patients with hematological malignancies included paraprotein-associated lesions (84.78%) and non-paraprotein-associated lesions (15.22%). The presence of nephrotic syndrome and an abnormal free light chain (FLC) ratio were independently associated with MGRS. The overall survival was better in patients with MGUS than in those with MGRS or hematological malignancies.
... total immunoglobulin measurement plays a role in the clinical management of MG. For example, in scenarios where the monoclonal protein migrates outside the gamma region (such as IgA) and may overlap with physiological globulins, the quantification by the electrophoresis method is made less reliable [34]. Besides that, total IgM quantification may also be used for monitoring waldenstrom's macroglobulinaemia if the monoclonal IgM is not easily measured by densitometry following electrophoresis analysis due to polymerization or other factors [35]. ...
Monoclonal gammopathy (MG) is a spectrum of diseases ranging from the benign asymptomatic monoclonal gammopathy of undetermined significance to the malignant multiple myeloma. Clinical guidelines and laboratory recommendations have been developed to inform best practices in the diagnosis, monitoring, and management of MG. In this review, the pathophysiology, relevant laboratory testing recommended in clinical practice guidelines and laboratory recommendations related to MG testing and reporting are examined. The clinical guidelines recommend serum protein electrophoresis, serum immunofixation and serum free light chain measurement as initial screening. The laboratory recommendations omit serum immunofixation as it offers limited additional diagnostic value. The laboratory recommendations offer guidance on reporting findings beyond monoclonal protein, which was not required by the clinical guidelines. The clinical guidelines suggested monitoring total IgA concentration by turbidimetry or nephelometry method if the monoclonal protein migrates in the non-gamma region, whereas the laboratory recommendations make allowance for involved IgM and IgG. Additionally, several external quality assurance programs for MG protein electrophoresis and free light chain testing are also appraised. The external quality assurance programs show varied assessment criteria for protein electrophoresis reporting and unit of measurement. There is also significant disparity in reported monoclonal protein concentrations with wide inter-method analytical variation noted for both monoclonal protein quantification and serum free light chain measurement, however this variation appears smaller when the same method was used. Greater harmonization among laboratory recommendations and reporting format may improve clinical interpretation of MG testing.
... Multiple myeloma (MM) is a malignant hematological disease caused by abnormal clonal proliferation of plasma cells (1). MM ranks second in hematological malignancies, which is considered to be incurable at present (2). About 80%-90% of MM patients will exhibit different degrees of MM-related bone diseases (3). ...
Background
Diffusion-weighted whole-body MRI (DW-MRI) is increasingly used to evaluate bone diseases of multiple myeloma (MM), but there is lack of quantitative indicator for DW-MRI to reflect the prognosis of MM. Apparent diffusion coefficient (ADC) values in DW-MRI has potential correlations between some indexes of MM, but the influence of ADC on MM survival needs to be further verified.
Methods
A total of 381 newly diagnosed MM patients were enrolled in the study to analyze the effect of ADC values in DW-MRI on progression-free survival (PFS) and overall survival (OS). The Kaplan–Meier method was used to perform univariate survival analysis, and the Cox proportional hazards model was used for multivariate analysis. In addition to the ADC value, genetic and serological indexes were also included.
Results
The survivals were observed in univariate ADC stratification with median PFS of 52.0, 45.0, 34.0, and 26.0 months (the unit of ADC value was 10⁻³ mm²/s; the ADC ranges were ADC < 0.4886, 0.4886 ≤ ADC < 0.6545, 0.6545 ≤ ADC < 0.7750, and ADC ≥ 0.7750; 95% CI, 43.759–62.241, 46.336–53.664, 39.753–46.247, and 27.812–32.188). The OS were 81.0, 61.0, 47.0, and 36.0 months (p < 0.001; 95% CI, 71.356–82.644, 67.630–70.370, 57.031–60.969, and 36.107–43.893). In Cox proportional hazards model, the ADC value was considered to be an independent risk factor affecting PFS and OS of MM (both p < 0.001).
Conclusions
This study supports that ADC in DW-MRI may independently stratify MM patients and better predict their prognosis. The combined use of DW-MRI and other parameters allows more accurate evaluation of MM survival.
Trial Registration
http://www.chictr.org.cn/showproj.aspx?proj=49012, ChiCTR2000029587.
... Although not specifically assessed here, quantification of total IgA using turbidimetry or nephelometry would also be expected to improve the CV as shown in previous studies. 8 9 Harmonising the gating strategy of performing perpendicular drop or tangent skimming may also reduce between-laboratory variation, 10 but this was not able to be assessed in our study. Others have not noted much variation between these two approaches, at least with moderate-sized paraproteins. ...
The Polish Society of Laboratory Diagnostics Working Group
recommendations for serum protein electrophoresis. 2023
Monoclonal gammopathy of undetermined significance (MGUS) is of considerable clinical importance to primary care physicians given its high prevalence in the general population. MGUS has a variable but lifelong risk for progression to hematologic cancer, such as multiple myeloma, Waldenström macroglobulinemia, or light-chain amyloidosis. In addition, MGUS has been associated with several nonmalignant yet symptomatic disorders that require therapy directed toward eliminating the monoclonal gammopathy. Thus, it is important not only to understand the essentials of diagnosing and monitoring patients with MGUS but also to recognize when to refer patients with MGUS to a specialist.
Monoclonal immunoglobulin produced by clonal plasma cells is the main cause in multiple myeloma and monoclonal gammopathy of renal significance. Because of the complicated purification method and the low stoichiometry of purified protein and glycans, site-specific N-glycosylation characterization for monoclonal immunoglobulin is still challenging. To profile the site-specific N-glycosylation of monoclonal immunoglobulins is of great interest. Therefore, in this study, we presented an integrated workflow for micro monoclonal IgA and IgG purification from patients with multiple myeloma in the HYDRASYS system, in-agarose-gel digestion, LC-MS/MS analysis without intact N-glycopeptide enrichment, and compared the identification performance of different mass spectrometry dissociation methods (EThcD-sceHCD, sceHCD, EThcD and sceHCD-pd-ETD). The results showed that EThcD-sceHCD was a better choice for site-specific N-glycosylation characterization of micro in-agarose-gel immunoglobulins (~2 μg) because it can cover more unique intact N-glycopeptides (37 and 50 intact N-glycopeptides from IgA1 and IgG2, respectively) and provide more high-quality spectra than sceHCD, EThcD and sceHCD-pd-ETD. We demonstrated the benefits of the alternative strategy in site-specific N-glycosylation characterizing micro monoclonal immunoglobulins obtained from bands separated by electrophoresis. This work could promote the development of clinical N-glycoproteomics and related immunology.
Achievement of a complete response (CR) in multiple myeloma (MM) correlates with improvement in survival outcomes; however, its impact on prognostic variables at baseline outside of clinical trial settings is not well described. We sought to determine the impact of achieving a CR within 2 years from diagnosis, its effect on the prognostic value of fluorescence in situ hybridization (FISH) and International Staging System (ISS) risk, and examined additional predictors of outcome among those achieving a CR in a routine clinical setting. We evaluated 1869 newly diagnosed MM patients who had ≥ 2 monoclonal protein immunofixation studies in the serum and urine available within 24 months from diagnosis, categorizing those with ≥ 2 negative serum and urine immunofixations as achieving CR. With a landmark at 24 months, median progression‐free survival (PFS) for CR versus non‐CR patients was 29.8 versus 20.9 months (p ≤ .0002); median overall survival (OS) was 104 versus 70 months (p < .0001). The impact of achieving a CR was retained after adjusting for FISH, ISS, sex, transplant status, and involved heavy chain. Baseline FISH and ISS stage were not associated with PFS or OS among patients achieving a CR. The following variables were found as predictors of inferior OS within the CR cohort: age > 75 years, male gender, hypoalbuminemia, and non‐immunoglobulin G involved heavy chain. Our study confirms that achievement of CR within 2 years from diagnosis is associated with improvement in survival outcomes and neutralization of the impact of FISH and ISS risk, thereby confirming observations from the clinical trial setting among a clinical practice cohort.
Extramedullary disease (EMM) represents a rare, aggressive and mostly resistant phenotype of multiple myeloma (MM). EMM is frequently associated with high-risk cytogenetics, but their complex genomic architecture is largely unexplored. We used whole-genome optical mapping (Saphyr, Bionano Genomics) to analyse the genomic architecture of CD138+ cells isolated from bone-marrow aspirates from an unselected cohort of newly diagnosed patients with EMM (n = 4) and intramedullary MM (n = 7). Large intrachromosomal rearrangements (> 5 Mbp) within chromosome 1 were detected in all EMM samples. These rearrangements, predominantly deletions with/without inversions, encompassed hundreds of genes and led to changes in the gene copy number on large regions of chromosome 1. Compared with intramedullary MM, EMM was characterised by more deletions (size range of 500 bp–50 kbp) and fewer interchromosomal translocations, and two EMM samples had copy number loss in the 17p13 region. Widespread genomic heterogeneity and novel aberrations in the high-risk IGH/IGK/IGL , 8q24 and 13q14 regions were detected in individual patients but were not specific to EMM/MM. Our pilot study revealed an association of chromosome 1 abnormalities in bone marrow myeloma cells with extramedullary progression. Optical mapping showed the potential for refining the complex genomic architecture in MM and its phenotypes.
