37: Multiple Myeloma and Other Plasma Cell Disorders

Key Points

• Disease summary:

  • Multiple myeloma (MM) is a plasma cell malignancy characterized by accumulation of clonal antibody-secreting plasma cells.

  • MM accounts for 1% of all cancers and 10% of all hematologic malignancies.

  • Almost all MM evolves from an asymptomatic premalignant stage termed as monoclonal gammopathy of undetermined significance (MGUS).

  • MM is now believed to be curable in only a small fraction of cases, and has a median overall survival of 5 years.

  • The major clinical manifestations are bone lesions, anemia, hypercalcemia, renal failure, and an increased risk of infections.

  • Genetic abnormalities are used for disease risk stratification and therapeutic decision making.

• Differential diagnosis:

  • Other hematologic disorders associated with monoclonal gammopathies, such as amyloidosis, Waldenström macroglobulinemia (WM) and polyneuropathy, organomegaly, endocrinopathy, M protein, and skin lesions (POEMS). Both IgM MGUS and WM represent fundamentally different disorders that arise from clonal cells different from the plasma cells.

• Monogenic forms:

  • No single gene cause of MM is known to exist.

• Family history:

  • Reports have described families with affected members in two or more generations, with two or more affected members in a single generation. First-degree family members of an MGUS affected individual have elevated risks of MGUS and MM.

• Twin studies:

  • Few studies report the occurrence of MM in monozygotic or dizygotic twins.

• Environmental factors:

  • Several studies have pointed to links between MM and environmental exposure to certain kinds of chemicals and radiation, however, most have been limited and there is no major environmental agent identified. It is currently believed that most MM is sporadic and not driven by genetic susceptibility or environmental factors.

• Genome-wide associations:

  • First genome-wide association studies (GWAS) have been recently published in MM. One study suggested that MM patients could be classified based on the germline single-nucleotide polymorphism (SNP) profiles into two distinct groups of good prognosis (>3 year progression-free survival [PFS]) and bad prognosis (<1 year PFS). Another study proposed the correlation of several SNPs with the clinical extent of the bone disease. Further validations are needed to confirm these findings.

Diagnostic Criteria and Clinical Characteristics

Diagnostic Criteria for MM

The diagnosis of MM requires 10% or more clonal plasma cells (PCs) on bone marrow examination or a biopsy-proven plasmacytoma, plus evidence of end-organ damage related to the underlying disorder. Organ damage is usually identified by the acronym CRAB, which includes

• C—calcium elevation (>11.5 mg/dL)

• R—renal dysfunction (creatinine >2 mg/dL)

• A—anemia (hemoglobin <10 g/dL)

• B—bone disease (lytic lesions or osteoporosis)

When MM is suspected clinically, diagnostic evaluation should include

• Blood and urine tests: Patients should be tested for the presence of monoclonal proteins in blood and urine by serum or urine protein electrophoresis, serum immunofixation, and serum-free light-chain (SFLC) assays.

• If M proteins are present, additional blood tests are recommended to measure blood cell ...