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A 73-year-old man was diagnosed as having multiple myeloma (MM), with serum protein electrophoresis (SPEP) and immunofixation (IF) showing a monoclonal (M) IgA κ at 0.3 g/dL and serum free κ/λ ratio skewed at 257. A computed tomographic scan showed lytic lesions, and bone marrow biopsy findings revealed 30% κ-restricted plasma cells. He was assigned to the bortezimib-lenalidomide-dexamethasone–elotuzumab (VRD-E) arm of a phase 3 trial. Three weeks after therapy initiation, follow-up SPEP-IF demonstrated an M-IgA κ at 0.1 g/dL. Two months later, SPEP-IF demonstrated a new M-IgG κ band in the same electrophoretic position as the M-IgA κ, with the 2 distinguishable only by IF and measured at 0.1 g/dL. Three months later, SPEP-IF demonstrated only the M-IgG κ, with the original M-IgA κ not detected. Over the next 8 months, the patient received maintenance therapy with VRD-E, and monthly SPEP-IF consistently showed M-IgG κ at 0.1 g/dL, with the original M-IgA κ consistently not detected. The serum free κ/λ ratio gradually decreased to 4.86 one year later. The Table summarizes assay data.
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D. Therapeutic monoclonal antibody at serum concentration detectable by SPEP-IF.
Serum protein electrophoresis separates serum proteins into the fractions albumin, α-, β-, and γ-globulins. It is used to detect monoclonal gammopathy in suspect cases of plasma cell dyscrasia or B-cell lymphoproliferative disorder (eg, Waldenstrom macroglobulinemia). Normal serum immunoglobulins form a polyclonal or Gaussian distribution in the γ-globulin region, while a monoclonal protein typically appears as a discrete single peak in the γ- or β-regions, the characteristic “M-spike.” When an M-spike is detected, IF is performed; this test uses anti–heavy chain and anti–light chain antisera to identify the M-protein isotype. The concentration and isotype of the M-protein can help distinguish MGUS (typically <3 g/dL) from overt MM (usually >3 g/dL) or B-cell lymphoma (usually IgM type). The sensitivity of SPEP for M-protein detection in MM is 87.6%,1 with 98.6% specificity for any monoclonal gammopathy (compared with IF).2 National Comprehensive Cancer Network guidelines for MM include SPEP and IF in diagnostic workup.3 Averaging $19.91 and $41.42, respectively, these tests are relatively inexpensive for disease monitoring.4
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Corresponding Author: Rose C. Beck, MD, PhD, Department of Pathology, University Hospitals of Cleveland Medical Center, 11100 Euclid Ave, RBC 568C, Cleveland, OH 44106 (firstname.lastname@example.org).
Published Online: September 7, 2017. doi:10.1001/jamaoncol.2017.2665
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank Susan Math, MT, for technical assistance. We thank Ehsan Malek, MD, and Nina Dambrosio, MSN, CNP, for help in manuscript preparation. They were not compensated for their assistance.
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