Clinical Review

Diagnosing Multiple Myeloma in Primary Care

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Primary care providers play a significant role in the diagnosis of multiple myeloma, a detrimental disease of insidious onset. Being aware of suspicious diagnostic indicators can make early detection easier—which is key for improving morbidity and mortality.




  • Presenting symptoms
  • Diagnostic tests
  • Differential diagnostic criteria

Multiple myeloma (MM) is a fatal, malignant neoplasm that originates in the plasma cells of bone marrow. A genetic mutation in the plasma cells creates myeloma cells, which replicate and produce monoclonal protein (M-protein). This accumulation of cells and abnormal protein can result in destruction and eventual marrow failure.1,2

MM’s insidious nature means it often goes undetected or misdiagnosed in its early stages; this delayed diagnosis can cause sequelae that limit quality of life. Furthermore, the five-year survival rate for myeloma varies by stage at which the disease is diagnosed: from 48% for distant (metastasized) myeloma to 71% for localized disease.3 It has also been noted that, in the past two decades, improvements in available treatment options and supportive care have contributed to a doubling of median survival time (from three years to six years).4 It is therefore paramount that providers be aware of MM and its signs to facilitate early diagnosis and treatment.


MM accounts for 1% of all cancers and about 10% of all hematologic malignancies.5 In 2017, the American Cancer Society estimated that more than 30,000 new cases of MM would be diagnosed in the United States.6 Additionally, MM was expected to cause more than 12,000 deaths last year.6

Median age at diagnosis is 69.3 In fact, 75% of men are older than 75 and 79% of women are older than 70 at diagnosis.1

Apart from age, other risk factors for MM have been identified but not fully explicated. For example, the disease is more common in men than in women (with men comprising two-thirds of new cases per year).3 MM is also two to three times more common in black than in white persons, making it the most common hematologic malignancy in this demographic group.3,7

The possibility of a genetic predisposition has also been studied. Several analyses have indicated an increased risk for MM in patients with a family history of the disease—as much as four times higher in those with an affected first-degree relative. This risk was further elevated in black compared with white patients (odds ratios, 17.4 and 1.5, respectively).7 However, many patients with MM have no relatives with this disorder.6,8


Almost all patients who develop MM also experience an asymptomatic premalignant stage called monoclonal gammopathy of undetermined significance (MGUS). MGUS is present in 3% to 4% of the general population older than 50 and is often an incidental finding. This stage almost always precedes MM—but because it is asymptomatic, only 10% of individuals diagnosed with MM have a known history of MGUS.8

In some patients, an asymptomatic intermediate stage called smoldering multiple myeloma (SMM) can be identified. SMM progresses to MM at a rate of 10% per year for the first five years; the rate decreases to 3% per year over the following five years, and 1% per year after that.8

MM is not curable, but as noted, the survival rate is steadily increasing due to rapidly evolving treatment regimens. Discussion of treatment is outside the scope of this article, but early diagnosis can improve quality of life and clinical outcomes and prolong life expectancy.

Multiple Myeloma in Bone Marrow image


The initial symptoms of MM can be nonspecific and may lead the provider to suspect a host of other conditions.2,6 (Those for advanced disease are also vague but tend to be more pronounced.) These may include fatigue, weakness, easy bruising or bleeding, and bone pain. Other common clinical manifestations of MM are anemia, chronic infection, bone disease, and/or renal failure.1,4 Patients may also experience loss of appetite, nausea, vomiting, increased thirst, and increased urination.9

Recent studies have shown that patients with SMM and/or MGUS also exhibit early signs of bone disease and increased risk for fracture.10 Eighty percent of patients who progress to MM have evidence of pathologic bone fractures.10 It is also possible for bones in the spine to weaken and collapse, pressing on the spinal nerves. This is known as spinal cord compression, which can manifest with sudden, severe back pain or numbness and/or muscle weakness (most often in the legs).6

MM must be included in the differential diagnosis, particularly when symptoms do not point to one specific disease process. Without early diagnosis, disease progression can result in complications such as bone fracture and osteoporosis, reduced kidney function, peripheral neuropathy, chronic anemia, and ultimately, death.2,6 The presence of bone fractures increases mortality risk by 20%.10

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