Clinical Progression of Small Monoclonal Abnormalities
Clinical Progression of Small Monoclonal Abnormalities
Monoclonal gammopathy of undetermined significance (MGUS) that presents with no quantifiable M spike on immunofixation electrophoresis (IFE) can be termed IFE MGUS. We retrospectively identified patients with IFE MGUS who were monitored with at least 1 subsequent assessment that included an IFE, and evaluated the persistence of the monoclonal protein and the progression of disease. Although the monoclonal proteins persisted in the majority of patients, 16% did not experience this persistence, and had no documented immunomodulatory therapy. After a median follow-up of 3.9 years, the disease clinically progressed in 14 patients (3.2%). Eight of these 14 patients with clinical progression had an immunoglobulin (Ig) A IFE M protein and 6 had an IgG M protein. This study demonstrates that in some patients with IFE MGUS, the M proteins are transient and that IgA IFE MGUS is more likely to persist and progress to myeloma.
Monoclonal gammopathy of undetermined significance (MGUS) is the most common plasma cell proliferative disorder. MGUS has a prevalence of more than 3% in the population of those aged 50 years or older and the prevalence increases to 5% or higher in those older than 70 years. If light-chain MGUS is included, the respective numbers are 4.2% and 6.6%. Although asymptomatic, a diagnosis of MGUS has long-term implications for the patient. The over-whelming majority of multiple myeloma cases are preceded by MGUS, and the rate of progression of MGUS to multiple myeloma or a related malignant condition is 1% per year. A serum monoclonal protein concentration of at least 1.5 g/dL (15 g/L) is one of the risk factors for progression.
To diagnose MGUS, the presence of a monoclonal immunoglobulin must be established by means of immunofixation electrophoresis (IFE). Serum protein electrophoresis (SPEP) is often used as the screening test for detecting monoclonal gammopathies and will trigger IFE confirmation. SPEP is also a method to quantitate and monitor the M protein; the M protein fraction is described as an M spike. If the concentration of the M protein is small or if the M protein migrates in the β or α fractions, the M protein becomes more challenging to detect. The limit of detection of M proteins with SPEP is 0.02 to 0.04 g/dL if they migrate in the γ fraction.
The quantitation of M proteins is a different process from the qualitative detection of M proteins. If a small M protein migrates within the β or α fractions or within a large polyclonal background, quantitation of the M protein will include substantial amounts of normal proteins. Quantitating an M spike in which the M protein may be less than 25% of the protein is inaccurate and may be misleading. These small monoclonal proteins are therefore often not quantitated and described only as small abnormalities. Although not quantifiable and more difficult to detect, subtle abnormalities such as fuzzy γ bands can reflect serious diseases. MGUS that presents with no quantifiable M spike but with an IFE abnormality can be termed IFE MGUS.
It is unclear if the outcomes of patients with IFE MGUS are comparable to those with MGUS with small (<1.5 g/dL [15 g/L]) M spikes. The goal of this study was to evaluate our laboratory and clinical experience in terms of persistence and progression of IFE MGUS in patients.
Abstract and Introduction
Abstract
Monoclonal gammopathy of undetermined significance (MGUS) that presents with no quantifiable M spike on immunofixation electrophoresis (IFE) can be termed IFE MGUS. We retrospectively identified patients with IFE MGUS who were monitored with at least 1 subsequent assessment that included an IFE, and evaluated the persistence of the monoclonal protein and the progression of disease. Although the monoclonal proteins persisted in the majority of patients, 16% did not experience this persistence, and had no documented immunomodulatory therapy. After a median follow-up of 3.9 years, the disease clinically progressed in 14 patients (3.2%). Eight of these 14 patients with clinical progression had an immunoglobulin (Ig) A IFE M protein and 6 had an IgG M protein. This study demonstrates that in some patients with IFE MGUS, the M proteins are transient and that IgA IFE MGUS is more likely to persist and progress to myeloma.
Introduction
Monoclonal gammopathy of undetermined significance (MGUS) is the most common plasma cell proliferative disorder. MGUS has a prevalence of more than 3% in the population of those aged 50 years or older and the prevalence increases to 5% or higher in those older than 70 years. If light-chain MGUS is included, the respective numbers are 4.2% and 6.6%. Although asymptomatic, a diagnosis of MGUS has long-term implications for the patient. The over-whelming majority of multiple myeloma cases are preceded by MGUS, and the rate of progression of MGUS to multiple myeloma or a related malignant condition is 1% per year. A serum monoclonal protein concentration of at least 1.5 g/dL (15 g/L) is one of the risk factors for progression.
To diagnose MGUS, the presence of a monoclonal immunoglobulin must be established by means of immunofixation electrophoresis (IFE). Serum protein electrophoresis (SPEP) is often used as the screening test for detecting monoclonal gammopathies and will trigger IFE confirmation. SPEP is also a method to quantitate and monitor the M protein; the M protein fraction is described as an M spike. If the concentration of the M protein is small or if the M protein migrates in the β or α fractions, the M protein becomes more challenging to detect. The limit of detection of M proteins with SPEP is 0.02 to 0.04 g/dL if they migrate in the γ fraction.
The quantitation of M proteins is a different process from the qualitative detection of M proteins. If a small M protein migrates within the β or α fractions or within a large polyclonal background, quantitation of the M protein will include substantial amounts of normal proteins. Quantitating an M spike in which the M protein may be less than 25% of the protein is inaccurate and may be misleading. These small monoclonal proteins are therefore often not quantitated and described only as small abnormalities. Although not quantifiable and more difficult to detect, subtle abnormalities such as fuzzy γ bands can reflect serious diseases. MGUS that presents with no quantifiable M spike but with an IFE abnormality can be termed IFE MGUS.
It is unclear if the outcomes of patients with IFE MGUS are comparable to those with MGUS with small (<1.5 g/dL [15 g/L]) M spikes. The goal of this study was to evaluate our laboratory and clinical experience in terms of persistence and progression of IFE MGUS in patients.
