Monoclonal gammopathy of undetermined significance and the risk of thrombotic events: Results from iStopMM, a prospective population-based screening study.

Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma and related diseases but has also been associated with thrombosis. Prior studies have not been based on screened cohorts leading to bias. We assessed the risk of thrombosis in a cohort of 75 422 individuals over 40 years old who were screened for MGUS in Iceland. We also evaluated the association of M protein concentration with thrombotic risk. A total of 3668 participants had MGUS. After a median follow-up of ~3.7 years, 124 venous and 252 arterial thrombotic events (10.3 and 21.0 per 1000 person years respectively) were observed in the MGUS group, compared to 1509 and 3471 in the non-MGUS group (6.0 and 13.8 per 1000 person years respectively). After adjusting for multiple confounders, MGUS was associated with an increased risk of venous thrombosis (hazard ratio [HR] = 1.43; 95% confidence interval [CI]: 1.19-1.73) but not arterial thrombosis (HR = 0.96; 95% CI: 0.87-1.13). M protein concentration was not associated with venous (p = 0.72) or arterial (p = 0.95) thrombosis. The findings show, in a screened cohort, that MGUS is associated with venous, but not arterial, thrombosis. Furthermore, they suggest that there is a subset of individuals with MGUS with subclinical monoclonal gammopathy of thrombotic significance.

Rögnvaldsson S ，Gasparini A ，Thorsteinsdottir S ，Sverrisdottir I ，Eythorsson E ，Long TE ，Palmason R ，Vidarsson B ，Onundarson PT ，Agnarsson BA ，Sigurdardottir M ，Olafsson I ，Thorsteinsdottir I ，Oskarsson JT ，Jonsson A ，Palsson R ，Indriðason OS ，Olafsson A ，Hultcrantz M ，Durie BGM ，Harding S ，Landgren O ，Love TJ ，Kristinsson SY ... -  《-》

Association Between Autoimmune Diseases and Monoclonal Gammopathy of Undetermined Significance : An Analysis From a Population-Based Screening Study.

Sverrisdottir I ，Thorsteinsdottir S ，Rognvaldsson S ，Aspelund T ，Vidarsson B ，Onundarson PT ，Agnarsson BA ，Sigurdardottir M ，Thorsteinsdóttir I ，Sveinsdottir SV ，Palmason R ，Olafsson I ，Sigurdsson F ，Thordardóttir AR ，Eythorsson E ，Jonsson A ，Palsson R ，Indridason OS ，Gislason GK ，Olafsson A ，Sigurdsson J ，Steingrímsdóttir H ，Einarsson Long T ，Hultcrantz M ，Durie BGM ，Harding S ，Landgren O ，Kristinsson SY ，Love TJ ... -  《-》

Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance : A Cohort Study Nested in a Clinical Trial.

Eythorsson E ，Rognvaldsson S ，Thorsteinsdottir S ，Einarsson Long T ，Reed ER ，Sigurdardottir GA ，Vidarsson B ，Onundarson PT ，Agnarsson BA ，Sigurdardottir M ，Olafsson I ，Thorsteinsdottir I ，Sveinsdottir SV ，Sigurdsson F ，Thordardottir AR ，Palsson R ，Indridason OS ，Jonsson A ，Gislason GK ，Olafsson A ，Sigurdsson J ，Steingrimsdottir H ，Hultcrantz M ，Durie BGM ，Harding S ，Landgren O ，Aspelund T ，Love TJ ，Kristinsson SY ... -  《-》

Monoclonal Gammopathy and Its Association with Progression to Kidney Failure and Mortality in Patients with CKD.

Little is known about the prognostic significance of monoclonal gammopathy of undetermined and renal significance (MGUS and MGRS) in patients with CKD. The objective of this study was to determine the clinical and kidney outcomes of patients with CKD with either MGUS or MGRS compared with those with CKD without MGUS or MGRS. We conducted a retrospective cohort study from 2013 to 2018. Patients who had both CKD diagnosis and monoclonal testing were identified. Patients were divided into MGRS, MGUS, and no monoclonal gammopathy groups. Cumulative incidence functions and Cox proportional hazards regression were used to model time to event data and to evaluate the association between monoclonal gammopathy status and risk of kidney failure, with death treated as a competing risk. Among 1535 patients, 59 (4%) had MGRS, 648 (42%) had MGUS, and 828 (54%) had no monoclonal gammopathy. Unadjusted analysis showed that compared with no monoclonal gammopathy patients, patients with MGRS were at higher risk of kidney failure (hazard ratio [HR] [95% confidence interval]: 2.5 [1.5 to 4.2] but not patients with MGUS (HR [95% confidence interval]: 1.3 [0.97 to 1.6]), after taking death into account as a competing risk. However, in the multivariable analysis, after adjusting for age, sex, eGFR, proteinuria, and Charlson Comorbidity Index, the risk of progression to kidney failure (with death as competing risk) in the MGRS group was no longer statistically significant (HR: 0.9 [0.5 to 1.8]). The same was also true for the MGUS group compared with the group with no monoclonal gammopathy (HR: 1.3 [0.95 to 1.6]). When evaluating the association between MGUS/MGRS status and overall survival, MGRS was significantly associated with mortality in fully adjusted models compared with the group with no monoclonal gammopathy, while MGUS was not. After adjusting for traditional risk factors, MGUS/MGRS status was not associated with a greater risk of kidney failure, but MGRS was associated with a higher risk of mortality compared with patients with no monoclonal gammopathy.

Sy-Go JPT ，Moubarak S ，Vaughan LE ，Klomjit N ，Viehman JK ，Fervenza FC ，Zand L ... -  《-》

Approaching hypercalcemia in monoclonal gammopathy of undetermined significance: insights from the iStopMM screening study.

Hypercalcemia in monoclonal gammopathy of undetermined significance (MGUS) presents a clinical challenge because it may indicate progression to multiple myeloma (MM) but could also be due to a multitude of unrelated disorders. To inform the approach to this clinical challenge, we conducted a nested cohort study within the Iceland Screens, Treats, or Prevents Multiple Myeloma screening study. Of the 75 422 Icelanders aged 40 years and above who underwent screening for MGUS, we included 2546 with MGUS who were in active follow-up, including regular serum calcium measurements. In total, 191 individuals (7.5%) had hypercalcemia detected at least once, of whom 93 had persistent hypercalcemia (48.7%). MM was found in 3 participants with persistent hypercalcemia (3.2%); all had concurrent bone disease and other end-organ damage. The most common causes of hypercalcemia were primary hyperparathyroidism (56.0%) and malignancies other than MM (16.0%). In this first comprehensive study on hypercalcemia in MGUS, we observed that hypercalcemia rarely indicated MGUS progression and never in the absence of other symptoms of MM. More than half of hypercalcemia cases were transient, and the underlying causes were similar to those in the general population. We conclude that hypercalcemia in MGUS should be approached in the same way as in those without MGUS.

Jónsdóttir ÁH ，Sigurjónsdóttir HÁ ，Thorsteinsdóttir S ，Long TE ，Sverrisdóttir IS ，Eythorsson E ，Óskarsson JÞ ，Palsson R ，Indridason OS ，Viðarsson B ，Onundarson PT ，Ólafsson Í ，Þorsteindóttir I ，Agnarsson BA ，Sigurðardóttir M ，Jónsson Á ，Hultcrantz M ，Durie BGM ，Harding S ，Landgren O ，Love TJ ，Kristinsson SY ，Rögnvaldsson S ... -  《-》