Publication Summary

Therapeutic antibody profiling in multiple myeloma by intact MALDI-ToF mass spectrometry

How intact mass spectrometry analysis identifies monoclonal antibody interference in myeloma monitoring - and why your lab needs reference m/z values.
Pello et al. demonstrated that intact Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-ToF) mass spectrometry using the EXENTTM System accurately differentiates 14 therapeutic antibodies - 6 monospecific and 8 bispecific - from endogenous monoclonal proteins (M-proteins) in multiple myeloma patients, outperforming immunofixation electrophoresis in sensitivity while maintaining high specificity.1

Key findings

What the study showed

01
14 therapeutic antibodies characterized

(6 monospecific and 8 bispecific) by intact MALDI-ToF MS — covering the major agents used in multiple myeloma and lymphoma treatment.1

02
Accurate measured m/z values

for all monoclonal antibodies (e.g., daratumumab: theoretical 11,692.0 vs. measured 11,691.1 ± 0.1 m/z unit).1

03
Higher sensitivity than IFE

for detecting therapeutic antibody interference, with high specificity maintained across all profiled agents1

04
Bispecifics resolved as dual m/z signatures

enabling differentiation from endogenous M-proteins that IFE cannot reliably achieve1

05
Longitudinal m/z tracking validated

consistent measured values across replicates support serial monitoring of treatment response.1

06
Designed for routine clinical workflows

Single-test detection of both monoclonal protein and therapeutic antibody.1

Therapeutic antibody m/z reference table

Theoretical and EXENT system-measured m/z values for therapeutic antibodies used in multiple myeloma, supporting accurate identification using intact mass spectrometry.1

Therapeutic Antibody Target Isotype Theoretical m/z Measured m/z
Daratumumab Anti-CD38 IgGκ 11,692.0 11,691.1 ± 0.1
Isatuximab Anti-CD38 IgGκ 11,745.1 11,744.5 ± 0.4
Elotuzumab Anti-SLAMF7 IgGκ 11,713.5 11,713.4 ± 0.3
Belantamab* Anti-BCMA IgGκ 11,816.2 11,815.4
Elranatamab Anti-BCMA / Anti-CD3 IgGκ / IgGκ 11,812.2 / 12,050.4 11,811.5 ± 0.3 / 12,049.6 ± 0.2
Teclistamab Anti-BCMA / Anti-CD3 IgGλ / IgGλ 11,318.0 / 11,312.2 11,317.6 ± 0.6 / 11,302.9 ± 0.4
Talquetamab Anti-GPRC5D / Anti-CD3 IgGκλ / IgGκλ 11,820.6 / 11,312.2 11,820.4 ± 0.1 / 11,303.3 ± 0.1
Linvoseltamab Anti-BCMA / Anti-CD3 IgGκ 11,709.0 11,708.4 ± 0.8
Etentamig Anti-BCMA / Anti-CD3 IgGκ 11,697.0 11,695.6 ± 0.1

 

*Belantamab determination performed in duplicate due to limited drug availability.1

Download the complete quick reference guide

This table covers the 9 core myeloma therapeutics assessed in the study. Download the complete quick reference guide for all 14 profiled therapeutics - including lymphoma-specific agents (brentuximab vedotin, epcoritamab, odronextamab), m/z values with standard deviations, and serum Cmax concentration ranges.

Download PDF guide

Why this matters

How can mass spectrometry improve myeloma treatment monitoring?

Mass spectrometry is redefining how clinical laboratories identify therapeutic monoclonal antibodies (tmAbs) in the serum of multiple myeloma patients.2,3

A study published in Biomedicines by Pello et al. demonstrates that intact MALDI-ToF MS analysis performed with the EXENT system can unambiguously distinguish monospecific and bispecific therapeutic antibodies from endogenous M-proteins.1

tmAbs — particularly IgG-based and bispecific agents — can interfere with immunofixation electrophoresis (IFE) interpretation, mimic disease proteins, and cause ambiguity in M-protein analysis.2-4 With the rising use of tmAbs in multiple myeloma treatment, addressing this interference is of growing importance in clinical diagnostics.2-4

This study profiled 14 therapeutic antibodies in total (6 monospecific and 8 bispecific) used in multiple myeloma and lymphoma treatment. Mass spectrometry-based profiling enabled accurate discrimination of therapeutic antibodies from endogenous M-proteins, outperforming IFE in sensitivity while maintaining high specificity.1

This enables laboratories to distinguish known therapeutic antibodies from patient-derived M-proteins based on precise molecular weight, eliminating the ambiguity inherent in IFE-based interpretation.1

This is particularly critical as bispecific antibodies — which produce two distinct light-chain signals — become standard of care in relapsed/refractory multiple myeloma.1,3 For clinical laboratories, this translates to more accurate response assessment, reduced false-positive M-protein detection during treatment, and a reliable method for longitudinal monitoring that integrates into existing workflows.1,4

ENABLING TECHNOLOGY

How the EXENT system enabled this study

The EXENT system is an automated mass spectrometry solution for identification, in conjunction with the Binding Site OptiliteTM IgG, IgA and IgM assays, and quantification of serum M-proteins, supporting routine diagnosis and monitoring of patients with monoclonal gammopathies including multiple myeloma.1,4

In this study, the EXENT system workflow enabled characterization of all 14 therapeutic antibodies reported, which in turn supports a more streamlined analytical workflow for laboratories.1

Explore the EXENT system

Source publication

Pello R, et al. Mass Spectrometry Profiling of Therapeutic Antibodies in Multiple Myeloma: m/z Features and Concordance with Immunofixation Electrophoresis. Biomedicines. 2025;13:2933.
Read the full publication in Biomedicines
References
  1. Pello R, Iglesias MÁ, López-Muñoz N, et al. Mass Spectrometry Profiling of Therapeutic Antibodies in Multiple Myeloma: m/z Features and Concordance with Immunofixation Electrophoresis. Biomedicines. 2025;13(12):2933. doi:10.3390/biomedicines13122933
  2. Murray DL, Puig N, Kristinsson S, et al. Mass spectrometry for the evaluation of monoclonal proteins in multiple myeloma and related disorders: an International Myeloma Working Group Mass Spectrometry Committee Report. Blood Cancer J. 2021;11(2):24. doi:10.1038/s41408-021-00408-4
  3. Kohlhagen MC, Barnidge DR, Murray DL. Clinical applications of mass spectrometry in multiple myeloma. Blood Adv. 2025;9(24):6593-6603. doi:10.1182/bloodadvances.2024015685
  4. Cristina Agullo, Noemi Puig, et al. SEMEDLAB and SEHH recommendations for monoclonal gammopathies by MALDI-TOF MS. Clin Chem Lab Med 2026 ; 64(3):586–599
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