Determining Why and Which Clinicians Order Serum Protein Electrophoresis (SPEP), Subsequent Diagnoses Based On Indications, and Clinical Significance of Routine Follow-up: a Study of Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS).
Authors: Doyle Leah M , Gundrum Jacob D , Farnen John P. , Wright Linda J. , Kranig Jo Ann I , Go Ronald S. 
Published: October 2019

Abstract
Abstract 4883

Background
MGUS is considered an incidental finding in the diagnostic work-up for multiple myeloma (MM) and related malignancies. Biologically, MGUS precedes all MM; however, its clinical significance and the utility of annual follow-up of these patients remain unknown. We studied a large series of MGUS patients to determine why clinicians ordered serum protein electrophoresis (SPEP) that resulted in an MGUS diagnosis, the subsequent diagnoses found based on test indications, and how malignant transformations are found.

Methods
Using our electronic medical database, we identified all MGUS patients diagnosed from January 1995-May 2009 at our institution. We excluded those who developed malignant transformation within 2 years of MGUS diagnosis. We reviewed the medical records to confirm the diagnosis and obtained relevant clinical data. To determine the likelihood of clinicians diagnosing a malignancy as a result of ordering SPEP, in recent years, we retrieved the number of patients with SPEP performed from 2004-2008 for indications other than follow-up of previously diagnosed MGUS, MM, and related malignancies.

Results
We found 361 MGUS patients with a median age at diagnosis of 74 years (range, 27-96). Fifty four percent were men and the median follow up time was 3 years (range, 0-37). The most common indications for monoclonal gammopathy testing were anemia (44%), bone symptoms/signs (20%), high creatinine (19%), elevated erythrocyte sedimentation rate (13%), and neuropathy (12%). Fifty-nine percent of patients had only 1 indication, 31% had 2 indications, and 10% had 3 or more indications. The departments that most commonly diagnosed MGUS were internal medicine (30%), hematology (19%), nephrology (11%), family practice (10%), and neurology (9%). The most common subsequent diagnoses were etiology unknown (22%), kidney disease (21%), chronic inflammation (12%), autoimmune conditions (9%), and iron deficiency (7%). The indications associated with an unknown diagnosis were anemia (38%), neuropathy (20%), and bone symptoms/signs (18%). Fifteen (4%) MGUS patients developed MM or a related malignancy at a median time of 4 years (range, 2-28). Of the transformations, 60% were detected because of symptoms and 40% were detected at scheduled MGUS follow-up. Of the 6 patients with malignant transformations detected at follow-up, 2 required treatment within a month of diagnosis, while 4 patients were observed for at least 6 months before initiating treatment. In 2004-2008, 7,090 patients had SPEP's performed to look for conditions associated with monoclonal gammopathy. This resulted in the diagnoses of 179 (3%) MGUS's and 89 (1%) malignancies.

Conclusions
At our institution, clinicians have a low threshold looking for malignancies associated with monoclonal gammopathy when evaluating elderly patients presenting with symptoms or signs seen in these conditions. This is despite the extremely low likelihood of finding one. For patients incidentally found to have MGUS, the rate of malignant transformation was low as expected; however, majority of transformations were found due to symptomatic presentations outside of scheduled follow-up visits. Our study calls into question the utility of the current practice of routinely following patients with MGUS.

Disclosures
No relevant conflicts of interest to declare.