Evaluation and Management of Elevated Monoclonal Protein in Older Adults

Initial Diagnostic Workup

The International Myeloma Society recommends serum protein electrophoresis (SPEP) with immunofixation to detect and characterize the monoclonal protein 4
The American Society of Clinical Oncology suggests 24-hour urine collection for protein electrophoresis and immunofixation to detect urinary light chains 2
Nephelometric quantification of IgG, IgA, and IgM immunoglobulins is recommended by the European Society for Medical Oncology 4
The National Comprehensive Cancer Network recommends serum free light chain (FLC) assay with kappa/lambda ratio for risk stratification and detection of light chain disease 1
Complete blood count is recommended by the American Society of Hematology to assess for anemia 2
Serum calcium and serum creatinine are recommended by the International Myeloma Society to detect hypercalcemia and renal insufficiency 2

The American College of Physicians recommends the following diagnostic criteria for MGUS: serum M-protein <30 g/L, clonal bone marrow plasma cells <10%, and absence of CRAB criteria 1
The European Society for Medical Oncology recommends the following diagnostic criteria for smoldering multiple myeloma: serum M-protein ≥30 g/L and/or clonal bone marrow plasma cells ≥10%, and absence of CRAB criteria 1
The American Society of Clinical Oncology recommends the following diagnostic criteria for active multiple myeloma: clonal bone marrow plasma cells ≥10% or biopsy-proven plasmacytoma, and evidence of end-organ damage (CRAB criteria) 3

The International Myeloma Society recommends the following follow-up protocol for low-risk MGUS: repeat SPEP at 6 months after initial diagnosis, and then every 2-3 years or when symptoms develop 1
The American Society of Hematology recommends the following follow-up protocol for intermediate/high-risk MGUS: SPEP and CBC at 6 months, and then annually for life 1
The National Comprehensive Cancer Network recommends the following follow-up protocol for smoldering multiple myeloma: testing 2-3 months after initial recognition, and then every 4-6 months for 1 year, and then every 6-12 months thereafter 2

The American College of Physicians recommends no immediate treatment for MGUS or SMM, except in cases of high-risk SMM or symptomatic myeloma 1
The European Society for Medical Oncology recommends treatment for active multiple myeloma, including induction therapy, autologous stem cell transplantation, and maintenance therapy 4

The American Society of Nephrology recommends evaluating for monoclonal protein in all adults with C3 glomerulopathy, especially those ≥50 years 7
The International Society of Nephrology recommends performing complement analysis even in absence of hypocomplementemia 7
The National Kidney Foundation recommends kidney biopsy to demonstrate monotypic immunoglobulin deposits or infer involvement in cases of suspected MGRS 8