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. 2018 Jan:51:66-71.
doi: 10.1016/j.clinbiochem.2016.09.015. Epub 2016 Sep 21.

Treatment of multiple myeloma with monoclonal antibodies and the dilemma of false positive M-spikes in peripheral blood

Kazunori Murata  1 , Samuel I McCash  2 , Brittany Carroll  2 , Alexander M Lesokhin  3 , Hani Hassoun  3 , Nikoletta Lendvai  3 , Neha S Korde  3 , Sham Mailankody  3 , Heather J Landau  4 , Guenther Koehne  4 , David J Chung  4 , Sergio A Giralt  4 , Lakshmi V Ramanathan  2 , Ola Landgren  3
Affiliations

Treatment of multiple myeloma with monoclonal antibodies and the dilemma of false positive M-spikes in peripheral blood

Kazunori Murata et al. Clin Biochem. 2018 Jan.

Abstract

Objectives: To characterize the effect of three humanized IgG κ monoclonal antibodies (daratumumab, isatuximab, and elotuzumab) on the interpretation of results generated by protein electrophoresis, immunofixation, free light chain, and heavy/light chain assays performed on human serum.

Methods: Healthy volunteer serum and serum from multiple myeloma patients were supplemented with clinically relevant concentrations of each of the three monoclonal antibodies. These specimens then underwent analysis via serum protein electrophoresis, immunofixation, serum free light chain quantification, heavy/light chain quantification, total IgG, and total protein. In addition, serum specimens from patients who had undergone treatment with elotuzumab for multiple myeloma underwent similar analysis.

Results: Addition of the study drugs to serum from both the healthy donor as well as multiple myeloma patients resulted in a visible and quantifiable M-protein on SPEP and a visible IgGκ band by IFE. Increases were also noted in total IgG, IgGκ, and IgGκ/IgGλ-ratios. Analysis of serum from multiple myeloma patients receiving study drug showed similar findings with an additional IgGκ band and quantifiable M-protein with similar migration patterns in specimens drawn after administration.

Conclusion: The treatment of multiple myeloma patients with monoclonal antibodies results in a visible and quantifiable M-protein that has the potential to falsely indicate poor response to therapy.

Keywords: Daratumumab; Electrophoresis; Elotuzumab; Immunofixation; Isatuximab; Myeloma.

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Figures

Figure 1
Figure 1
Serum protein electrophoresis and immunofixation of specimens supplemented with various anti-myeloma therapeutic mAbs. a-d: Serum from a healthy volunteer (a), with 834 ug/mL isatuximab (b), with 707 ug/mL daratumumab (c), with 625 ug/mL elotuzumab (d). e-g: Serum from a multiple myeloma patient in remission (e), with 707 ug/mL daratumumab (f), with 625 ug/mL elotuzumab (g) h-j: Serum from a multiple myeloma patient with a visible M-spike by protein electrophoresis and immunofixation (h) , with 707 ug/mL daratumumab (i), with 625 ug/mL elotuzumab (j)
Figure 2
Figure 2
Serum protein electrophoresis and immunofixation of serum drawn from patients treated with elotuzumab. a, b: Myeloma patient A serum 1 week post dose 4 (2a), 1 week post dose 12 (2b) c, d: Myeloma patient B serum 1 week post dose 3 (2c) , and 1 week post dose 6 (2d) e-g: Myeloma patient C serum pre dose 1 (2e), 1 week post dose 3 (2f), 1 week post dose 4 (2g)
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