History and exam
Key diagnostic factors
common
anemia
Occurs in 60% to 70% of patients.[5][6]
Anemia (>2 g/dL below the lower limit of normal, or <10 g/dL) is one of the subsidiary diagnostic criteria for MM (according to the International Myeloma Working Group).[3][4] See Classification.
uncommon
monoclonal gammopathy of undetermined significance (MGUS)
Other diagnostic factors
common
hypercalcemia
Hypercalcemia may be present in up to 20% of patients at the time of MM diagnosis.[67][68]
Hypercalcemia (serum calcium >1 mg/dL higher than the upper limit of normal, or >11 mg/dL) is one of the subsidiary diagnostic criteria for MM (according to the International Myeloma Working Group).[3][4] See Classification.
infections
Normal immunoglobulin production is impaired, resulting in a relative hypogammaglobulinemia, predisposing patients to infections.
Infection rates vary with treatment status. Severe infection has been reported in up to 23% of patients receiving immunomodulatory drugs (e.g., thalidomide or lenalidomide).[69][70]
fatigue
Due to anemia or hypercalcemia.
renal impairment
Occurs in up to 50% of patients, and is associated with a poor prognosis.[5][64]
Renal insufficiency (creatinine clearance <40 mL per minute or serum creatinine >2 mg/dL) is one of the subsidiary diagnostic criteria for MM (according to the International Myeloma Working Group).[3][4] See Classification.
Risk factors
strong
monoclonal gammopathy of undetermined significance (MGUS)
MM is preceded by MGUS.
MGUS is an asymptomatic disorder that is usually diagnosed incidentally when a monoclonal protein is detected in the serum or urine. It is present in approximately 2% to 3% of the white population at ages 50 years and older.[19][36][37]
The risk of progression of MGUS to MM or related disorders is approximately 1% per year; the initial concentration of serum monoclonal protein is a significant predictor of progression at 20 years.[19][20][21][22]
Other independent prognostic factors influencing progression of MGUS to MM include: immunoglobulin A (IgA); bone marrow plasmacytosis >5%; Bence Jones proteinuria; decrease in polyclonal serum immunoglobulin; and elevated erythrocyte sedimentation rate.[38][39][40]
abnormal free light-chain ratio
An abnormal free light-chain ratio (kappa/lambda ratio <0.26 or >1.65) is a significant prognostic indicator for progression from MGUS to MM.[41]
weak
male sex
Incidence of MM in the US is higher among men than women (8.7 vs. 5.9 per 100,000 persons [2017-2021 data]).[9]
black ethnicity
Incidence of MM in the US is highest among non-Hispanic black people and lowest among non-Hispanic Asian/Pacific Islanders.[9]
family history of MM
Families with two or more affected individuals have been reported.[11]
A study by the International Multiple Myeloma Consortium found an increased risk of MM in those with a first-degree relative with any lymphohematopoietic cancer, especially MM.[10] Risk of MM in those with a first-degree relative with MM was more evident among men and African-Americans.
radiation exposure
A large epidemiologic study among nuclear industry workers reported a borderline-significant association between MM and protracted low doses of ionizing radiation.[13]
One subsequent epidemiologic study (22,373 radiation workers with 536,126 person-years of follow-up) found no indication of a relationship with external gamma radiation or internal plutonium (alpha) radiation exposure (following inhalation) and MM incidence.[42]
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