How I Treat In Brief
For all other patients with MGUS , we perform BM biopsy and skeletal imaging at the time of diagnosis .
Follow-Up After Diagnosis
The purpose of follow-up is to detect early progression of MGUS into LPM , with the expectation that timely treatment will minimize major complications and prolong survival . Despite a lack of prospective data from randomized trials , clinical practice guidelines recommend annual follow-up for most patients with MGUS , given the seriousness of LPM complications and the relative ease of testing for M-proteins .
We recommend that all patients be reassessed with complete blood count , SPEP , FLC , calcium , and creatinine testing six months after MGUS diagnosis to determine clinical stability and detect rapidly evolving LPM . ( See FIGURE 2 for a suggested algorithm for follow-up .)
After initial follow-up , patients with low-risk MGUS need further evaluation only if concerning symptoms or LPMs develop ( including anemia , cardiomyopathy , hypercalcemia , or neuropathy ); all other patients should have an annual follow-up . Patients with a life expectancy of less than 5 years or those older than 80 years may not need this follow-up .
Progression After MGUS Diagnosis
A rising M-protein or serum FLC level should raise concern about disease progression , but these elevations are seen in only about 50 percent of patients with MGUS prior to progression . Even when a change occurs , its significance is challenging to interpret if it is not accompanied by symptoms or alterations in other laboratory parameters , such as hemoglobin , calcium , or creatinine .
In addition to changes in M-protein level , progression should be considered in the presence of any of the following unexplained signs and symptoms : anemia , cardiomyopathy ( restrictive ), diarrhea , fracture , hepatomegaly , hypercalcemia , hyperviscosity ( in the setting of IgM
M-protein ), intestinal pseudo-obstruction , lytic lesion , macroglossia , nephrotic syndrome , neuropathy ( autonomic , sensory , or motor ), purpura , and renal insufficiency .
Any concern for progression should prompt additional testing , such as imaging studies or BM or tissue biopsy . Current diagnostic criteria for MM allow a diagnosis to be made prior to end-organ damage and enable the use of advanced imaging for early detection of bone disease .
Harms of MGUS Diagnosis
The potential harms associated with an MGUS diagnosis are rarely a topic of doctor ’ s office conversation or even academic debate . However , paying more attention to the psychologic distress conferred by an MGUS diagnosis is warranted , as it is similar to the distress associated with diagnosis of a malignancy .
Overdiagnosis of LPMs is also inevitable , but the harms of overtreatment and surveillance have yet to be studied in MGUS .
The cost of MGUS follow-up – estimated to be more than $ 100 million annually in the U . S . – is substantial and cannot be ignored . Tests should be performed only in patients in whom there is clear suspicion of certain LPMs or conditions known to be associated with M-protein .
Future Directions
We expect that the number of Americans living with a diagnosis of MGUS will rise from approximately 500,000 to well over one million in the next 30 years , yet there is surprisingly limited evidence to inform best clinical practice for the extent of initial evaluation and subsequent followup care .
To fill this gap , we need studies in populations that are at the highest risk of developing MGUS and a better understanding of biomarkers that predict the risk of transformation to malignant disease .
While the hematology community awaits this type of research , we should harness the power of machine-learning methods to analyze existing big data accumulated from patients with MGUS to collect more information about how and in whom MGUS evolves to malignant disease . Further evidence will help reduce
FIGURE 1 . Algorithm for Bone Marrow Biopsy and Skeletal Imaging
• Low risk (< 1.5 gm / dL , lgG type , normal FLC ratio ), or
• lgM < 1.5 gm / dL , or
• Light chain MGUS with FLC ratio < 8
Uncomplicated
Bone marrow biopsy and skeletal survey may be deferred
Suspected MGUS
Presence of unexplained symptoms or laboratory features of concern
Bone marrow biopsy required ; Skeletal survey ( low dose whole body CT or conventional radiographs ) required in non-lgM patients
FIGURE 2 . Algorithm for Follow-up of MGUS
Stable patient anxiety and define optimal followup and preventive strategies . ●
All patients with MGUS
Follow-up in 6 months
All other patients
Possible progression
Fast Facts
Risk stratification #
Work-up for lymphoplasmacytic malignancy
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✓✓The discovery of MGUS is most often incidental and made by nonhematologists .
✓✓There is international consensus on the criteria for diagnosis of the three subtypes of MGUS ( IgM MGUS , non-IgM MGUS , and lightchain MGUS ).
✓✓Despite the high prevalence of MGUS , there is limited evidence to inform best clinical practice for initial evaluation and subsequent follow-up care .
✓✓MGUS is considered an obligate precursor to several LPMs , so longterm follow-up is generally recommended .
✓✓The potential harms associated with an MGUS diagnosis include psychological distress and the cost of follow-up .
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Low risk |
Intermediate or high risk |
No malignancy |
Malignancy |
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No MGUS follow-up ; usual medical care
Annual MGUS follow-up ; CBC , calcium , creatine , SPEP , FLC
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Mayo Clinic Risk Stratification Model ; CBC = complete blood count
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Manage accordingly |
54 ASH Clinical News July 2018