Monoclonal Gammopathies and Multiple Myeloma

Challenges with traditional monitoring

Monitoring of monoclonal proteins in MM is based on the concept of measurable disease

If a patient with myeloma produces monoclonal protein measurable by serum protein electrophoresis (SPEP) (≥10 g/L (1 g/dL)) or urine protein electrophoresis (UPEP) (≥200 mg/24-hour urine), then the International Myeloma Working Group (IMWG) recommends regular monitoring with these methods.1

If a patient is not measurable by these methods at baseline, but has an involved serum free light chain (sFLC) of at least 100 mg/L and an abnormal sFLC ratio, the patient may be monitored by sFLC according to IMWG guidelines.1

Multiple Myeloma (MM) and the Monoclonal Gammopathies that precede it can be challenging to monitor using traditional methods for several reasons2

 

Sensitivity

Electrophoretic methods may not be sensitive enough to detect small changes in monoclonal protein levels, especially in early stages of the disease. This can cause false negative results, leading to delays in detecting underlying disease and in initiation of treatment.2

Co-migrate

Electrophoresis is prone to a range of problems; monoclonal proteins can co-migrate with other serum proteins making quantification difficult. Besides this, precipitation of proteins in the sample, dye saturation, non-linearity and broad or multiple peaks on the gel can make quantification of monoclonal proteins very challenging.

Interpretation

SPEP and IFE (immunofixation electrophoresis) rely on subjective interpretation of protein bands, and subtle changes may be missed or interpreted as background noise. This can cause inaccuracies and potentially impact the quality of results.3,4,.5

Variability and subjectivity

Another challenge is the variability and subjectivity in interpretation of SPEP and IFE results, this inter-observer variability can lead to inconsistent results between laboratories. This can be a particular concern when monitoring patients, as changes in protein levels may be difficult to interpret if there is inconsistency in how the results are interpreted.3,4

Time consuming and labor intensive

In addition, SPEP and IFE are time-consuming and labor-intensive. Samples must be processed and analysed in a timely manner and repeated testing may be required to confirm results or detect changes over time. This can become a burden on laboratory resources and increase healthcare costs for the patients.3,4

Use Freelite® assays to address these challenges

Serum free light chain (sFLC) assays can be used alongside electrophoretic methods even when monoclonal protein measurable by serum protein electrophoresis (SPEP) (≥10 g/L (1 g/dL)) or urine protein electrophoresis (UPEP) (≥200 mg/24-hour urine).

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Monitoring and diagnosing MM and AL Amyloidosis
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Hevylite® assays can be used

to monitor the changes in the involved immunoglobulin by their unique quantification of IgG, IgA and IgM heavy and light chain isotypes.3,4,5 These techniques offer improved analytical sensitivity compared to traditional SPEP and IFE methods and may aid in the monitoring of patients over time.3,4

Freelite® and Hevylite® assays should be used in conjunction with SPEP and IFE as they offer clinicians and laboratory professionals advanced monitoring tools to allow objective quantification of monoclonal proteins, and measurement at lower concentrations than traditional methods, for the best possible care for their patients6, 7. 

 

Freelite and Hevylite assays
The optimal combination for the management of monoclonal gammopathy patients
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The EXENT® GAM Assay*

The assay empowers clinicians to effectively diagnose and monitor patients with monoclonal gammopathies throughout the treatment journey with a simple serum test.  

 This offers the opportunity to:

• Detect M-protein at diagnosis in patients that would not be detected by electrophoretic methods8,9

• Monitor patients’ disease below the sensitivities of conventional methods, potentially removing the need for invasive bone marrow assessments10,11

• Specifically track a patient’s disease and differentiate it from oligoclonal banding and therapeutic antibody interference to improve the assignment of treatment response12-15

• Detect biochemical relapse and help identify patients at risk of early progression16

• Identify clinically relevant information such as post translational modifications and secondary clones17

Find out more about how you can use EXENT GAM Assay
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Freelite® assays
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Detect and monitor Multiple Myeloma with Freelite assays
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Analyze Heavy/Light Chain Istotype with Hevylite assays


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Abbreviations and Acronyms
Definitions  
HLC

Heavy-light chain
IFE

Immunofixation
MM

Multiple myeloma
IMWG

International Myeloma Working Group
SPEP

Serum protein electrophoresis
UPEP

urine protein electrophoresis
References
  1. Kumar S, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 2016; 17:e328-46
  2. Keren DF. Protein electrophoresis in clinical diagnosis. 2012, ASCP Press.
  3. Keren DF & Schroeder L. Challenges of measuring monoclonal proteins in serum. Clin Chem Lab Med 2016; 54:947-961
  4. Prisi S, et al. Unraveling the Possibilities of Monoclonal Protein Migration, Identification, and Characterization in SPEP on Capillary Zone Electrophoresis. J Lab Physicians 2022; 14:505-510
  5. Katzmann JA, et al. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem 2002; 48:1437-1444 https://www.frontiersin.org/articles/10.3389/fimmu.2020.625753
  6. Dejoie T, et al. Responses in multiple myeloma should be assigned according to serum, not urine, free light chain measurements. Leukemia 2019; 33:313-318
  7. Michallet M, et al. Heavy+light chain monitoring correlates with clinical outcome in multiple myeloma patients. Leukemia 2018; 32:376-382
  8. Giles HV, et al. Redefining nonmeasurable multiple myeloma using mass spectrometry. Blood 2022; 139:946-95
  9. Immunoglobulin Isotypes (GAM) for the EXENT Analyser Instructions for Use
  10. Puig N, et al. Clinical Impact of next generation flow in bone marrow Vs QIP-Mass spectrometry in peripheral blood to assess minimal residual disease in newly diagnosed multiple myeloma patients receiving maintenance as part of the GEM2014MAIN Trial. Blood; Presented at ASH 2022; 140:866a
  11. Puig N, et al. Analysis of treatment efficacy in the GEM-CESAR trial for high-risk smoldering multiple myeloma patients: Comparison between the standard and IMWG MRD criteria and QIP-MS including FLC (QIP-FLC-MS). J Clin Oncol 2020; 38:8512a
  12. Berlanga O, et al. Two cases of multiple myeloma achieving complete remission but presenting residual M-protein by the EXENT® solution. Presented at AACC 2023; B371a
  13. Puig N, et al. QIP-Mass Spectrometry in high risk smoldering multiple myeloma patients included in the GEM-CESAR Trial: Comparison with Conventional IMWG Response Assessment. Presented at AACC 2020; B-341a
  14. Derman BD, et al. Comparison of monoclonal gammopathy assessed by mass spectrometry vs. serum protein immunofixation in peripheral blood in Multiple Myeloma. Presented at AACC 2020; B-351aa
  15. Lajko M, et al. Using QIP-MS to distinguish a therapeutic mAb from an endogenous M-protein in patients being treated for multiple myeloma. Presented at AACC 2018; A-328a
  16. Mai EK, et al. Implications and prognostic impact of mass spectrometry in patients with newly-diagnosed multiple myeloma. Blood; Presented at ASH 2022; 140:968a
  17. Dispenzieri A, et al. N-glycosylation of monoclonal light chains on routine MASS-FIX testing is a risk factor for MGUS progression. Leukemia 2020

*EXENT GAM Assay refers to Immunoglobulin Isotypes (GAM) for the EXENT® Analyser.