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A simple method to distinguish residual elotuzumab from monoclonal paraprotein in immunofixation assays for multiple myeloma patients

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Abstract

Negative immunofixation electrophoresis (IFE) of serum and/or urine is a diagnostic marker for determining a complete response (CR) after immunotherapy for multiple myeloma (MM). However, residual therapeutic antibodies such as elotuzumab (IgG-κ), can compromise IFE evaluation when the affected immunoglobulins belong to the same IgG-κ subclass. We thus sought to develop a simple and rapid method to treat patient serum before IFE to distinguish the residual elotuzumab. Serum samples from patients receiving elotuzumab were treated with a predetermined amount of soluble signaling lymphocyte activation molecule F7 (SLAMF7) protein and then subjected to conventional IFE testing. We tested our method in samples from 12 patients. The IgG-κ band in IFE disappeared or shifted after elotuzumab treatment in four patients with no bone marrow minimal residual disease and normalized free light chain, whereas seven patients with any sign of residual MM showed a remaining IgG-κ band after treatment. One-hour incubation of samples with 6–9 molar excess soluble SLAMF7 before IFE was sufficient to distinguish residual elotuzumab in 11 of 12 samples. This simple method does not require special reagents, can be performed in most clinical laboratories, and enables differentiation between patients with a CR and those requiring further treatment.

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Abbreviations

ASADA:

Antigen-specific therapeutic monoclonal antibody depletion assay

BM:

Bone marrow

CR:

Complete response

FLC:

Free light chain

IFE:

Immunofixation electrophoresis

MRD:

Minimal residual disease

mAbs:

Monoclonal antibodies

M-protein:

Monoclonal immunoglobulin protein

MM:

Multiple myeloma

SLAM7:

Signaling lymphocyte activation molecule F7

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Funding

This work was supported by the Bristol-Myers Squibb endowed Chair in Cancer Biomarker Research (D.S. and Y.A.)

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Correspondence to Yoshiki Akatsuka.

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Conflict of interest

Daisuke Sugiyama, Hiroyoshi Nishikawa, and Yoshiki Akatsuka received research funding from Bristol-Myers Squibb for this study. The remaining authors declare no competing financial interests.

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Chen, S., Kiguchi, T., Nagata, Y. et al. A simple method to distinguish residual elotuzumab from monoclonal paraprotein in immunofixation assays for multiple myeloma patients. Int J Hematol 113, 473–479 (2021). https://doi.org/10.1007/s12185-021-03088-9

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