scholarly journals A risk‐stratification model based on the initial concentration of the serum monoclonal protein and MYD 88 mutation status identifies a subset of patients with IgM monoclonal gammopathy of undetermined significance at high risk of progression to Waldenström macroglobulinaemia or other lymphoproliferative disorders

2019 ◽  
Vol 187 (4) ◽  
pp. 441-446 ◽  
Author(s):  
Marzia Varettoni ◽  
Silvia Zibellini ◽  
Emanuela Boveri ◽  
Catherine Klersy ◽  
Chiara Candido ◽  
...  
Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4496-4496
Author(s):  
Holly Lee ◽  
Lesley Street ◽  
Jason Tay ◽  
Jennifer Grossman ◽  
John F Thaell ◽  
...  

Abstract Introduction Monoclonal gammopathy of undetermined significance (MGUS) is a prevalent hematological condition among elderly population with incidence rates of 3% and 5% over the age of 50 and 70 years, respectively (Kyle et al., 2018). It is considered a premalignant state of multiple myeloma with a risk of progression of 1% per year. It has also been shown that MGUS patients have a shorter survival compared to the age- and sex-matched cohort (Kyle et al., 2018). Recent reports have highlighted the clinical significance of monoclonal gammopathy and the organ injury that may result from the effects of paraproteinemia (Fermand et al., 2018). With new insights into the significance of monoclonal gammopathy, the purpose of our study was to characterize the MGUS patient population referred at our hematology clinics by observing the reason for monoclonal protein testing and assessing patient comorbidities at the time of MGUS diagnosis. Methods We collaborated with three different clinicians who see the majority of MGUS patients at the University of Calgary Medical Group (UCMG) clinics. Patients who were referred and diagnosed with MGUS at the hematology clinic at UCMG since 2014 were assessed. Retrospective chart reviews were performed and reasons for monoclonal testing were recorded as indicated in referral request notes or initial consult notes. Data on patient comorbidities was collected as indicated in the initial consult notes. MGUS risk stratification was calculated per previous reports (Katzmann et al., 2013; Kyle et al., 2018) Results A total of 606 MGUS patients were seen at our clinic from February 2014 to June 2018. There were 565 patient charts available for complete review. 56% of the patients were male. Median age was 72 and median follow up was 2 years. MGUS risk stratification showed that 33.2% had low, 47.9% intermediate-low, 17.8% intermediate-high, and 1.2% high-risk MGUS. There were 55.5% IgG-MGUS, 20.5% IgM-MGUS, 12.3% IgA-MGUS, and 8.4% light chain-MGUS patients. 3% had biclonal gammopathy. Patient comorbidities at time of diagnosis are reported in table 1. The most common conditions were hypertension (50.4%), dyslipidemia (33.1%), chronic kidney disease (22.4%), diabetes (21.6%), coronary artery disease (18.6%), and solid tumors (14.6%). The most common solid tumors were prostate cancer (22/ 83, 25%), colon cancer (12/83, 14.4%), and breast cancer (10/83, 12.0%). Of the 565 patient charts, 140 had either missing referral sheets or had no record of the reasons for paraproteinemia investigations in the notes. In the rest of the 425 patients, the most common reason for monoclonal protein testing by referring physician was for renal dysfunction, which included work up for acute kidney injury, chronic kidney injury, proteinuria and hematuria. The next most common reason was work up of neuropathy, followed by anemia, and constitutional symptoms (figure 1). The patients in the 'Others' group had various reasons for testing including work up for seizure, forgetfulness, stroke, headache, chronic pancreatitis, multiple sclerosis, myasthenia gravis, family history of myeloma, history of venous thromboembolism, splenomegaly, bronchiectasis, chest pain, and as part of routine physical and blood donor testing. Discussion and Conclusion MGUS is often incidentally detected as part of a work up for other medical conditions, and our results reveal that there is a variety of reasons for which monoclonal testing is performed. With recent developments in our understanding of the significance of monoclonal gammopathy and its association with certain renal and organ damage (Fermand et al., 2018; Leung et al., 2012), there may be a change in how the paraproteinemia investigations are utilized by clinicians in different disciplines. It will be important to recognize and establish appropriate indications for testing. Furthermore, MGUS patients present with a wide range of comorbidities at the time of diagnosis. Interdisciplinary care will play a key role in discerning how much of the organ dysfunction and patients' symptoms are secondary to their underlying medical conditions versus the effect of monoclonal gammopathy. Disclosures McCulloch: Celgene: Honoraria; Takeda: Other: Travel expenses. Neri:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5045-5045
Author(s):  
Leonard J. Horwitz ◽  
Beth Faiman ◽  
Paul Elson ◽  
Rachid Baz ◽  
Mohamad Hussein ◽  
...  

Abstract Abstract 5045 Observation remains the standard approach to patients with monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic multiple myeloma (AMM) who lack end-organ impairment characteristic of symptomatic MM. Institution of early MM therapy has not been shown to improve survival or alter the natural progression of the disease. Cyclooxygenase-2 (COX2) inhibitors inhibit proliferation and induce apoptosis in drug resistant MM cell lines. 23 asymptomatic adult patients with a serum monoclonal protein >1g/dL, from Cleveland Clinic, Mayo Clinic, or University of Arkansas Medical Center between August 2005 and April 2008 were randomized to either celecoxib or placebo in a double-blind, 1:1 fashion. The primary end point was change in the monoclonal protein concentration after 6 months. Correlative biomarkers, including IL6 and IL-6R, CD4/CD8+ T-cell ratios, and beta-2 microglobulin, were examined before and after treatment. Celecoxib had no significant effect on the median monoclonal protein concentration, which went from a median of 1. 44 to 1. 65 g/dL with placebo and 2. 42 to 2. 24 g/dL with Celecoxib (p=0. 36), or on any of the analyzed correlative markers (all p-values >0. 34). One patient's monoclonal protein concentration increased on placebo, but he did not require treatment for symptomatic MM. There were no adverse events of Grade 2 or higher. Celecoxib was well tolerated in contrast to previous reports when given in higher doses and in combination with thalidomide. Although accrual was limited we conclude that celecoxib has no clinical or immunologic effect on high risk asymptomatic plasma cell disorders. This study does not support using celecoxib for preventing progression to symptomatic MM. Future studies on progression of MGUS to symptomatic MM would require more patients and a longer follow-up period. Disclosures: Off Label Use: Celecoxib for chemoprophylaxis. Hussein:Celgene: Employment. Reu:Celgene: Research Funding.


2009 ◽  
Vol 41 (7) ◽  
pp. 547-558 ◽  
Author(s):  
Andrés Jerez ◽  
Francisco José Ortuño ◽  
María del Mar Osma ◽  
Ignacio Español ◽  
Ana Dolores González ◽  
...  

Blood ◽  
2003 ◽  
Vol 102 (10) ◽  
pp. 3759-3764 ◽  
Author(s):  
Robert A. Kyle ◽  
Terry M. Therneau ◽  
S. Vincent Rajkumar ◽  
Ellen D. Remstein ◽  
Janice R. Offord ◽  
...  

AbstractLittle effort has been made to quantitate adverse outcomes of monoclonal gammopathy of undetermined significance (MGUS) of the immunoglobulin M (IgM) class, which progresses to lymphoma or Waldenström macroglobulinemia, whereas IgA and IgG MGUS progress to multiple myeloma, primary amyloidosis (AL), or a related plasma cell disorder. From 1960 to 1994, IgM MGUS was diagnosed in 213 patients in southeastern Minnesota. The end point was progression to lymphoma or a related disorder, as assessed with the Kaplan-Meier method. The 213 patients were followed up for 1567 person-years (median, 6.3 years per patient). Lymphoma developed in 17 patients (relative risk [RR], 14.8), Waldenström macroglobulinemia in 6 (RR, 262), primary amyloidosis in 3 (RR, 16.3), and chronic lymphocytic leukemia in 3 (RR, 5.7). The relative risk of progression was 16-fold higher in the patients with IgM MGUS than in the white population of the Iowa Surveillance, Epidemiology, and End Results Program. Cumulative incidence of progression was 10% at 5 years, 18% at 10 years, and 24% at 15 years. On multivariate analysis, the serum monoclonal protein and serum albumin concentrations at diagnosis were the only risk factors for progression to lymphoma or a related disorder. Risk for progression to lymphoma or a related disorder at 10 years after the diagnosis of MGUS was 14% with an initial monoclonal protein concentration of 0.5 g/dL or less, 26% with 1.5 g/dL, 34% for 2.0 g/dL, and 41% for more than 2.5 g/dL. (Blood. 2003;102:3759-3764)


2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 207-207
Author(s):  
Swarup Kumar ◽  
Radhika B Kulkarni ◽  
Gonca Ozcan ◽  
Asha Tipirneni ◽  
Ritika Vankina ◽  
...  

207 Background: Monoclonal Gammopathy of Undetermined Significance (MGUS) is an asymptomatic premalignant condition that can be a precursor to multiple myeloma and lymphoproliferative disorders. There exists no best practice for the workup of MGUS, despite the number of patients diagnosed every year. We evaluated the workup of MGUS patients at a University Hospital Hematology clinic before and after implementation of an algorithm based on the Mayo Clinic Risk Stratification Model. Methods: This was a single-center IRB-approved retrospective study. Charts of 132 patients referred for MGUS were reviewed across two groups (A: June 2019 -May 2020 and B: June-Dec 2020). Use of the Mayo Clinic Risk Stratification Model for MGUS was implemented in May 2020. Data regarding initial work up, bone marrow studies and imaging were collected. Statistical analyses were performed using R software for computing (4.0.4). Results: Patient demographics and those who did not need further work up per the algorithm are summarized in table. All 86 new (100%) referrals had an initial CBC, creatinine, calcium, SPEP, and IFE while 7(8.1%) did not have an FLC assay. 43(50%) patients had a 24-hour urine protein electrophoresis. 65.1% (56/86) [group A: 26; group B: 30] met the criteria for no extended workup; 39.3% of these (22/56) underwent imaging while 7.1% (4/56) underwent bone marrow exam. After implementation of the algorithm, the number of patients who underwent imaging studies decreased from 50% (13/26) to 30% (9/30). Skeletal survey was the most ordered imaging modality (90.1%,20/22). Conclusions: Our study highlights the overutilization of imaging studies in low-risk MGUS patients. Approximately 50% of patients with MGUS are low risk with a lifetime risk of progression being less than 2%. In these patients avoiding extensive testing will minimize costs without adversely affecting clinical outcomes. We recommend a dedicated MGUS clinic to improve workup and monitoring of these patients. [Table: see text]


2020 ◽  
Vol 10 (10) ◽  
Author(s):  
María-Victoria Mateos ◽  
Shaji Kumar ◽  
Meletios A. Dimopoulos ◽  
Verónica González-Calle ◽  
Efstathios Kastritis ◽  
...  

Abstract Smoldering multiple myeloma (SMM) is an asymptomatic precursor state of multiple myeloma (MM). Recently, MM was redefined to include biomarkers predicting a high risk of progression from SMM, thus necessitating a redefinition of SMM and its risk stratification. We assembled a large cohort of SMM patients meeting the revised IMWG criteria to develop a new risk stratification system. We included 1996 patients, and using stepwise selection and multivariable analysis, we identified three independent factors predicting progression risk at 2 years: serum M-protein >2 g/dL (HR: 2.1), involved to uninvolved free light-chain ratio >20 (HR: 2.7), and marrow plasma cell infiltration >20% (HR: 2.4). This translates into 3 categories with increasing 2-year progression risk: 6% for low risk (38%; no risk factors, HR: 1); 18% for intermediate risk (33%; 1 factor; HR: 3.0), and 44% for high risk (29%; 2–3 factors). Addition of cytogenetic abnormalities (t(4;14), t(14;16), +1q, and/or del13q) allowed separation into 4 groups (low risk with 0, low intermediate risk with 1, intermediate risk with 2, and high risk with ≥3 risk factors) with 6, 23, 46, and 63% risk of progression in 2 years, respectively. The 2/20/20 risk stratification model can be easily implemented to identify high-risk SMM for clinical research and routine practice and will be widely applicable.


2021 ◽  
Vol 11 (6) ◽  
Author(s):  
A. Visram ◽  
C. Soof ◽  
S. V. Rajkumar ◽  
S. K. Kumar ◽  
S. Bujarski ◽  
...  

AbstractSoluble BCMA (sBCMA) levels are elevated in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the association between sBCMA levels and prognosis in MGUS and SMM has not been studied. We retrospectively analyzed sBCMA levels in stored samples from 99 MGUS and 184 SMM patients. Baseline sBCMA levels were significantly higher in MGUS and SMM patients progressing to MM during clinical follow up. When stratified according to the median baseline sBCMA level for each cohort, higher levels were associated with a shorter PFS for MGUS (HR 3.44 comparing sBCMA ≥77 vs <77 ng/mL [95% CI 2.07–5.73, p < 0.001] and SMM (HR 2.0 comparing sBCMA ≥128 vs <128 ng/mL, 95% 1.45–2.76, p < 0.001) patients. The effect of sBCMA on PFS was similar even after adjusting for the baseline MGUS or SMM risk stratification. We evaluated paired serum samples and found that sBCMA increased significantly in MGUS and SMM patients who eventually progressed to MM, whereas among MGUS non-progressors the sBCMA level remained stable. While our results require independent validation, they suggest that sBCMA may be a useful biomarker to identify MGUS and SMM patients at increased risk of progression to MM independent of the established risk models.


Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5412-5417 ◽  
Author(s):  
Ola Landgren ◽  
Robert A. Kyle ◽  
Ruth M. Pfeiffer ◽  
Jerry A. Katzmann ◽  
Neil E. Caporaso ◽  
...  

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma-cell proliferative disorder associated with a life-long risk of progression to multiple myeloma (MM). It is not known whether MM is always preceded by a premalignant asymptomatic MGUS stage. Among 77 469 healthy adults enrolled in the nationwide population-based prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we identified 71 subjects who developed MM during the course of the study in whom serially collected (up to 6) prediagnostic serum samples obtained 2 to 9.8 years prior to MM diagnosis were available. Using assays for monoclonal (M)–proteins (electrophoresis/immunofixation) and kappa-lambda free light chains (FLCs), we determined longitudinally the prevalence of MGUS and characterized patterns of monoclonal immunoglobulin abnormalities prior to MM diagnosis. MGUS was present in 100.0% (87.2%-100.0%), 98.3% (90.8%-100.0%), 97.9% (88.9%-100.0%), 94.6% (81.8%-99.3%), 100.0% (86.3%-100.0%), 93.3% (68.1%-99.8%), and 82.4% (56.6%-96.2%) at 2, 3, 4, 5, 6, 7, and 8+ years prior to MM diagnosis, respectively. In approximately half the study population, the M-protein concentration and involved FLC-ratio levels showed a yearly increase prior to MM diagnosis. In the present study, an asymptomatic MGUS stage consistently preceded MM. Novel molecular markers are needed to better predict progression to MM in patients with MGUS.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xuehua Xi ◽  
Ying Wang ◽  
Luying Gao ◽  
Yuxin Jiang ◽  
Zhiyong Liang ◽  
...  

BackgroundThe incidence and mortality of thyroid cancer, including thyroid nodules &gt; 4 cm, have been increasing in recent years. The current evaluation methods are based mostly on studies of patients with thyroid nodules &lt; 4 cm. The aim of the current study was to establish a risk stratification model to predict risk of malignancy in thyroid nodules &gt; 4 cm.MethodsA total of 279 thyroid nodules &gt; 4 cm in 267 patients were retrospectively analyzed. Nodules were randomly assigned to a training dataset (n = 140) and a validation dataset (n = 139). Multivariable logistic regression analysis was applied to establish a nomogram. The risk stratification of thyroid nodules &gt; 4 cm was established according to the nomogram. The diagnostic performance of the model was evaluated and compared with the American College Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS), Kwak TI-RADS and 2015 ATA guidelines using the area under the receiver operating characteristic curve (AUC).ResultsThe analysis included 279 nodules (267 patients, 50.6 ± 13.2 years): 229 were benign and 50 were malignant. Multivariate regression revealed microcalcification, solid mass, ill-defined border and hypoechogenicity as independent risk factors. Based on the four factors, a risk stratified clinical model was developed for evaluating nodules &gt; 4 cm, which includes three categories: high risk (risk value = 0.8-0.9, with more than 3 factors), intermediate risk (risk value = 0.3-0.7, with 2 factors or microcalcification) and low risk (risk value = 0.1-0.2, with 1 factor except microcalcification). In the validation dataset, the malignancy rate of thyroid nodules &gt; 4 cm that were classified as high risk was 88.9%; as intermediate risk, 35.7%; and as low risk, 6.9%. The new model showed greater AUC than ACR TI-RADS (0.897 vs. 0.855, p = 0.040), but similar sensitivity (61.9% vs. 57.1%, p = 0.480) and specificity (91.5% vs. 93.2%, p = 0.680).ConclusionMicrocalcification, solid mass, ill-defined border and hypoechogenicity on ultrasound may be signs of malignancy in thyroid nodules &gt; 4 cm. A risk stratification model for nodules &gt; 4 cm may show better diagnostic performance than ACR TI-RADS, which may lead to better preoperative decision-making.


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