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


CONCLUSIONS
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.
Clinical Chemistry Service, Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, United States. Electronic address: muratak@mskcc.org.
Kazunori
K
Murata
Clinical Chemistry Service, Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, United States.
Samuel I
SI
McCash
Clinical Chemistry Service, Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, United States.
Brittany
B
Carroll
Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, United States.
Alexander M
AM
Lesokhin
Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, United States.
Hani
H
Hassoun
Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, United States.
Nikoletta
N
Lendvai
Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, United States.
Neha S
NS
Korde
Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, United States.
Sham
S
Mailankody
Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275, York, Ave. New York, NY 10065, United States.
Heather J
HJ
Landau
Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275, York, Ave. New York, NY 10065, United States.
Guenther
G
Koehne
Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275, York, Ave. New York, NY 10065, United States.
David J
DJ
Chung
Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275, York, Ave. New York, NY 10065, United States.
Sergio A
SA
Giralt
Clinical Chemistry Service, Department of Laboratory Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, United States.
Lakshmi V
LV
Ramanathan
Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065, United States.
Ola
O
Landgren
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001797:Blood Protein Electrophoresis / Q000379:methods; D016022:Case-Control Studies; D005189:False Positive Reactions; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000097:blood / Q000628:therapy*; D009194:Myeloma Proteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D009194:Myeloma Proteins; C085016:multiple myeloma M-proteins
Daratumumab; Electrophoresis; Elotuzumab; Immunofixation; Isatuximab; Myeloma
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