Mass spectrometry for the evaluation of monoclonal proteins in multiple myeloma and related disorders: an International Myeloma Working Group Mass Spectrometry Committee Report
Plasma cell disorders (PCDs) are identified in the clinical lab by detecting the monoclonal immunoglobulin (M-protein) which they produce. Traditionally, serum protein electrophoresis methods have been utilized to detect and isotype Mproteins. Increasing demands to detect low-level disease and new therapeutic monoclonal immunoglobulin treatments have stretched the electrophoretic methods to their analytical limits. Newer techniques based on mass spectrometry (MS) are emerging which have improved clinical and analytical performance. MS is gaining traction into clinical laboratories, and has replaced immunofixation electrophoresis (IFE) in routine practice at one institution. The International Myeloma Working Group (IMWG) Mass Spectrometry Committee reviewed the literature in order to summarize current data and to make recommendations regarding the role of mass spectrometric methods in diagnosing and monitoring patients with myeloma and related disorders. Current literature demonstrates that immune-enrichment of immunoglobulins coupled to intact light chain MALDI-TOF MS has clinical characteristics equivalent in performance to IFE with added benefits of detecting additional risk factors for PCDs, differentiating Mprotein from therapeutic antibodies, and is a suitable replacement for IFE for diagnosing and monitoring multiple myeloma and related PCDs. In this paper we discuss the IMWG recommendations for the use of MS in PCDs.
Important points:
- Mass spectrometry (MS) is a valuable tool for the detection and monitoring of monoclonal proteins in multiple myeloma and related disorders.
- The International Myeloma Working Group has updated criteria for the diagnosis of multiple myeloma.
- Screening panels and assays have been developed for the detection of monoclonal gammopathies.
- Serum reference intervals and diagnostic ranges have been established for free kappa and free lambda immunoglobulin light chains.
- Serum-free light chain analysis is recommended for evaluating response in light-chain multiple myeloma.
- Consensus recommendations have been provided for the standard investigative workup in multiple myeloma.
- Criteria for response and minimal residual disease assessment in multiple myeloma have been established.
- Multiparameter flow cytometry and deep sequencing methods can be used for minimal residual disease detection in multiple myeloma.
- Mass spectrometry-based methods can be used for the identification, monitoring, and quantification of M-proteins in multiple myeloma.
- Nanobody enrichment coupled with MALDI-TOF mass spectrometry and LC-MRM MS are techniques used for the assessment of minimal residual disease in multiple myeloma.
- Mass spectrometry can detect and monitor monoclonal proteins in various conditions, including systemic light chain amyloidosis and gamma heavy chain disease.
- Monoclonal gammopathy of undetermined significance (MGUS) can be detected and monitored using mass spectrometry-based methods.
- Glycosylation of immunoglobulin light chains and N-glycosylation on routine MASS-FIX testing are risk factors for MGUS progression.
- MALDI-TOF mass spectrometry can distinguish daratumumab from M-proteins.
- MASS-FIX can eliminate false positives in myeloma due to therapeutic monoclonal antibody interference.
- Blood-based M-protein detection using MASS-FIX is highly sensitive in patients with multiple myeloma.
- MALDI-TOF mass spectrometry analysis can be used for tracking measurable residual disease in multiple myeloma patients.
- MS methods have improved clinical and analytical performance compared to electrophoretic methods for M-protein detection.
- MS can aid in the diagnosis and monitoring of plasma cell disorders, including multiple myeloma and AL amyloidosis.
- MS has the potential to improve the sensitivity of M-protein detection and guide treatment decisions in multiple myeloma and related disorders.
Authors:
David L. Murray, Noemi Puig, Sigurdur Kristinsson, Saad Z. Usmani, Angela Dispenzieri, Giada Bianchi, Shaji Kumar, Wee Joo Chng, Roman Hajek, Bruno Paiva, Anders Waage, S. Vincent Rajkumar and Brian Durie
Citation:
Blood Cancer J. 2021 Feb 1;11(2):24.
Doi: 10.1038/s41408-021-00408-4.