Monoclonal Gammopathies: Multiple myeloma and Related Disorders

• Monoclonal gammopathy of undetermined significance (MGUS) : Requires the simultaneous presence of 1) A monoclonal spike < 3 g/dL on serum protein electrophoresis, 2) Bone marrow infiltration by monoclonal malignant plasma cells < 10%, and 3) Absence of end-organ damage related to multiple myeloma (CRAB: hyperCalcemia, Renal failure, Anemia, and Bone lesions). Affects ~3% of individuals older than 50 years. There is a 1%/year lifelong risk of transformation to a hematologic malignancy (mainly multiple myeloma).
• Smoldering multiple myeloma (SMM): Also known as asymptomatic myeloma. Requires a monoclonal spike ≥ 3 g/dL and/or bone marrow infiltration by monoclonal malignant plasma cells ≥ 10% in the absence of end-organ damage (CRAB: hyperCalcemia, Renal failure, Anemia, and Bone lesions). There is a 10%/year risk of progression to active multiple myeloma or related plasma cell dyscrasia in the first 5 years, 3%/year in the following 5 years, and 1%/year thereafter.
• Multiple myeloma: Requires three criteria be satisfied: 1) A monoclonal spike on serum protein electrophoresis or urine protein electrophoresis or an abnormal free light chain ratio, 2) Bone marrow infiltration by monoclonal malignant plasma cells or presence of a plasmacytoma (see below), and 3) End-organ damage related to multiple myeloma (CRAB: hyperCalcemia, Renal failure, Anemia, and Bone lesions) or hyperviscosity, amyloidosis, or recurrent infections
• Nonsecretory multiple myeloma: ~3% of all multiple myeloma. No monoclonal spike is present on serum or urine protein electrophoresis
• Solitary plasmacytoma: Variant of plasma cell dyscrasia characterized by a single area of monoclonal plasma cell proliferation in the absence of systemic disease (e.g., CRAB) and bone marrow involvement. Can be osseous or extraosseous. May have a small monoclonal component, but generally a monoclonal spike is not present on serum or urine protein electrophoresis.
• Multiple solitary plasmacytomas: Can occur in ~5% of patients with a solitary plasmacytoma. No evidence of bone marrow involvement or other skeletal lesions. May be recurrent.
• Plasma cell leukemia: Peripheral blood circulating plasma cells > 2 × 10⁹/L or 20% of leukocytes. Can either be primary (60% of cases) or secondary to leukemic transformation of preexisting multiple myeloma.

Other conditions that can present with a monoclonal spike include chronic lymphocytic leukemia, B-cell and T-cell lymphomas, chronic myeloid leukemia, and other plasma cell dyscrasias, such as amyloid light chain amyloidosis, Waldenström macroglobulinemia, and heavy chain disease.

References

• Bianchi G, Ghobrial IM. Does My Patient with a Serum Monoclonal Spike have Multiple Myeloma? Hematol Oncol Clin North Am. 2012 Apr;26(2):383-93.
• International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003 Jun;121(5):749-57.