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A New Monoclonal Protein Detected in a Patient With Myeloma Undergoing Elotuzumab Therapy

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

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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Article Information

Corresponding Author: Rose C. Beck, MD, PhD, Department of Pathology, University Hospitals of Cleveland Medical Center, 11100 Euclid Ave, RBC 568C, Cleveland, OH 44106 (rose.beck@uhhospitals.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.

References
1.
Katzmann  JA, Kyle  RA, Benson  J,  et al.  Screening panels for detection of monoclonal gammopathies.  Clin Chem. 2009;55(8):1517-1522.PubMedGoogle ScholarCrossref
2.
Katzmann  JA, Clark  R, Sanders  E, Landers  JP, Kyle  RA.  Prospective study of serum protein capillary zone electrophoresis and immunotyping of monoclonal proteins by immunosubtraction.  Am J Clin Pathol. 1998;110(4):503-509.PubMedGoogle ScholarCrossref
3.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology, Multiple Myeloma Version 3. 2017. https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed January 19, 2017.
4.
2017 Clinical diagnostic laboratory fee schedule. Centers for Medicare and Medicaid Services. CMS.gov. https://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/ClinicalLabFeeSched/Clinical-Laboratory-Fee-Schedule-Files.html. Downloaded January 29, 2017.
5.
Mills  JR, Murray  DL.  Identification of friend or foe: the laboratory challenge of differentiating M-proteins from monoclonal antibody therapies.  J Appl Lab Med. 2017;1(4):421-431. doi:10.1373/jalm.2016.020784Google Scholar
6.
van de Donk  NW, Moreau  P, Plesner  T,  et al.  Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma.  Blood. 2016;127(6):681-695.Google ScholarCrossref
7.
Murata  K, McCash  SI, Carroll  B,  et al.  Treatment of multiple myeloma with monoclonal antibodies and the dilemma of false positive M-spikes in peripheral blood.  Clin Biochem. 2016;(Sept):S0009-9120(16)30312-5. doi:10.1016/j.clinbiochem.2016.09.015PubMedGoogle Scholar
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