A case of hereditary transthyretin amyloidosis cardiomyopathy complicated with monoclonal gammopathy of undetermined significance

The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.

Results of the promise study from ~30,000 individuals screened for monoclonal gammopathies

Udgivelsesdato: 2009-Oct

Introduction: Monoclonal gammopathy of unknown significance (MGUS) is a premalignant disorder preceding multiple myeloma that is present in 2.4% of the general population ages 50 years or older. MGUS can be categorized into conventional MGUS that includes IgM MGUS and non-IgM MGUS, and light chain MGUS (defined as those with abnormal free light chain ratio with complete lack of immunoglobulin heavy chain expression on immunofixation). Our objective was to investigate the prognosis of MGUS patients by clinical subgroup and risk stratification suggested by Mayo Clinic. Methods: Data is obtained from National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999-2004, a nationally representative health survey with follow-up mortality data updated in December 2011. Subjects who were diagnosed with MGUS were included in the study. They were divided into three groups; IgM MGUS, non-IgM MGUS, and light chain MGUS (LC-MGUS). Median overall survival of three groups was obtained using log-rank test and age-adjusted hazard ratio for death between the groups was obtained using cox-proportional regression model. Finally, we also analyzed median survival and age adjusted hazard ratio on conventional MGUS subjects by Mayo clinic MGUS risk stratification based on risk factors of M-protein>1.5g/dL, non-IgG MGUS, and abnormal free light chain (FLC) ratio. Analyses were performed in R software version 3.2.2, and a P-value <0.05 was considered statistically significant. Results: 22,523 subjects in the cohort were screened for MGUS with serum protein electrophoresis, serum protein immunofixation, serum FLC assay, and M-protein typing. There were 483 subjects with MGUS (47 IgM-MGUS, 385 non-IgM MGUS, and 51 LC-MGUS). The median ages of total MGUS subjects, and subgroups were 70, 72.3, 69 and 73 years old, respectively. Median follow-up was 116 months. Median overall survival was 117 months for IgM MGUS, 173 months for non-IgM MGUS, and 109 months for LC-MGUS (p = 0.03). However, the age adjusted hazard ratio (aHR) did not show significant difference between the sub-groups. Likewise, median overall survival of Mayo Clinic MGUS risk group 0, 1, 2 and 3 was 185 months, 163 months, 137 months, and 76.5 months, respectively (p <0.001). Only high-risk group (risk of 3) showed statistically significant aHR 2.9 (95%CI 1.5∼5.6) compared with low risk group (risk of 0). Conclusion: There was no statistically significant mortality difference between MGUS subgroup. Only high-risk group defined by the Mayo Clinic MGUS risk stratification showed inferior survival and higher risk of death compared to rest of MGUS subjects. Further prospective studies are needed to validate our findings and to investigate whether early interventions for MGUS patients by clinical subgroup and risk stratification are needed rather than the current standard management of watchful-waiting. Citation Format: Hyun-Seok Kim, Jieqi Liu, Brittany L. Gladney, Neil Kothari, Noa Biran, Victor Chang, David S. Siegel. Survival prognosis of MGUS patients by clinical and risk subgroup: a result from a nationally representative prospective cohort. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2639.

Multicenter Descriptive Study of Monoclonal Gammopathy of Undetermined Significance in Patients with Heart Failure

Effects of Monoclonal Gammopathy of Undetermined Significance (MGUS) on Outcomes after Solid Organ Transplant

Monoclonal Gammopathy of Undetermined Significance (MGUS) Does Not Affect Outcomes in Patients Undergoing Solid Transplants.

Association between soluble immune biomarkers and monoclonal gammopathy of undetermined significance (MGUS) in three large cancer epidemiology cohorts with participants from underrepresented groups.

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

Monoclonal Gammopathy of Undetermined Significance and Risk of Chronic Kidney Disease: Results of the Population-Based Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) Study

Health Care Burden of Monogammopathy of Renal Significance

Platelet RNA Splicing Profiles Can Distinguish IgM MGUS Patients from Healthy Individuals

Background Monoclonal gammopathy of undetermined significance (MGUS) is a pre-malignant disorder with a progression risk to multiple myeloma of 1% per year. Patients with MGUS may produce monoclonal intact immunoglobulins (Ig) and/or free light chains (FLC). The International Myeloma Working Group (IMWG) recommendations for the use of FLC measurements in MGUS are to establish the diagnosis of light chain only MGUS (LC-MGUS) and further to risk-stratify newly diagnosed MGUS. Once identified, MGUS is longitudinally monitored at intervals dependent on the risk of transformation. The IMWG recommends serum protein electrophoresis (SPEP) for monitoring of known MGUS with intact Ig, however others have published benefits of additionally monitoring with FLC. In this study, we evaluated the diagnostic sensitivity and specificity of the Optilite® Freelite® Kappa Free Kit and the Optilite Freelite Lambda Free Kit (The Binding Site, part of Thermo Fisher Scientific) in patients with MGUS, and the monitoring performance of Freelite results measured in serial samples from patients with clinically stable and progressive MGUS. Methods Serum samples from 234 patients with clinically diagnosed MGUS and 140 disease controls, taken at single time points, and serial samples (≥3) from 49 patients with MGUS were tested with the Freelite assays. Intact M-protein presence and isotype was confirmed in MGUS samples with immunofixation electrophoresis (IFE). In patients clinically diagnosed with LC-MGUS, the presence of detectable M protein on IFE was not required. The disease control cohort (non-MGUS) had disorders commonly associated with elevated polyclonal immunoglobulins (e.g autoimmune, liver, and renal diseases), confirmed by total IgG and/or IgA and/or IgM results and the absence of M-protein by IFE. Patients represented a diverse population from both European and US sources. Results The overall diagnostic sensitivity of the Optilite Freelite assays was 59.4%, calculated as the frequency of abnormal free light chain ratio (rFLC) in intact immunoglobulin MGUS, and abnormal rFLC with concurrent elevated involved FLC level in LC-MGUS. The diagnostic sensitivity was: 58.0% in non-IgM MGUS, 41.7% in IgM MGUS, 66.7% in biclonal MGUS and 100% in LC-MGUS. In intact (IgG/IgA/IgM) kappa MGUS, the diagnostic sensitivity was 67.5%, versus 41.5% in intact (IgG/IgA/IgM) lambda MGUS. The diagnostic specificity was 86.4%. In the 49 patients with serial samples, concentrations of involved FLC were stable in 93.3% of patients with clinically stable MGUS, whereas in patients with clinically progressive MGUS an increasing trend was seen in 50% of cases. Conclusions These results demonstrate that the Optilite Freelite Kappa and Lambda assays produce clinically relevant results that are useful in the evaluation of MGUS.

Monoclonal Gammopathy of Undetermined Significance and the Risk of Thrombotic Events: Results from Istopmm, a Population-Based Screening Study in Iceland

Monoclonal gammopathy of undetermined significance: to screen or not to screen for multiple myeloma? – response