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Frequently asked questions

A groundbreaking approach to monoclonal protein identification

For patients at risk of plasma cell disorders, early identification is critical to ensure better outcomes. Coined as MASS-FIX, our innovative approach uses matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and marks the first major breakthrough in multiple myeloma screening since gel electrophoresis was developed in 1967. 

And now with further advancements, the availability of MASS-FIX quantitation (Mayo ID: QMPSS).

What is QMPSS testing?

Test code QMPSS has replaced test codes DMOGA, TMOGA, PEISO, SPEP, and MALD. M-protein quantitation (formerly known as protein electrophoresis) is now being performed by MALDI-TOF similar to M-protein isotyping (MASS-FIX). This is an improved methodology to the standard protein electrophoresis and includes quantitation of monoclonal-protein isotype and immunoglobulins G, A, and M.

What is the advantage of quantifying the monoclonal protein utilizing QMPSS?

QMPSS testing is able to quantify to a lower threshold than traditional protein electrophoresis.  One of the benefits of greater sensitivity for quantification is that clinicians can be more confident when negative results are obtained.

What are the advantages of MASS-FIX over other methodologies?

By weighing M-proteins, MASS-FIX overcomes electrophoresis’s limitations in detection and provides the most accurate understanding of a patient’s M-proteins. This novel testing also helps healthcare providers understand their patients’ risk of progression to multiple myeloma or AL amyloidosis. This level of insight is not possible via traditional testing methods.

What test code(s) should I order for diagnostic or monitoring patient cases?

At diagnosis, order Mayo ID: QMPSS and Mayo ID: FLCS. For monitoring, order Mayo ID: QMPSS.

How sensitive is MASS-FIX testing, and what is the lowest quant number that can be reported with QMPSS?

Research has shown that MASS-FIX is 10x more sensitive and specific than immunofixation.  QMPSS’ LOQ is 0.01 g/dL. This highlights the increased specificity of the assay and provides even more confidence when negative results are received.

If a clinician performs protein electrophoresis in-house and previously sent MALD testing to Mayo Clinic, can they just order MASS-FIX isotyping?

QMPSS performs both monoclonal protein quantitation and isotyping at the same time. MALD is no longer available as an orderable. The addition of measuring the IgG, IgA, and IgM allows us to better interpret the spectra that is detected. In the MALD assay, only peaks could be seen but without quantitation values. With the addition of quants, we are able to tell if a peak rises to the level to which it needs to be called or ignored.

Does QMPSS eliminate the IgA beta migration issue present in SPEP?

Yes. Studies reveal that 40% of the IgA M-proteins migrate within the beta region of the SPEP. This means that other proteins are included in the SPEP quantitation. However, QMPSS does not have this issue, thus all patients can be followed by this test. In addition, QMPSS is not affected by the presence of fibrinogen, which can produce fall M-spikes.

Mayo Clinic has internally verified the equivalence of M-protein measurements by MASS-FIX method to SPEP. While the methods are equivalent, the analytical measuring range is significantly extended using QMPSS. Internal studies have shown the M-protein quantitation to be linear over a range of 0.004 g/dL to 7.10 g/dL. Our analytical CVs at an M-protein level of 0.020 g/dL was demonstrated to be below 105. Our SPEP assay was linear over a much shorter range (0.4 to 4.5 g/dL). In Mayo Clinic’s practice, 75% of our positive samples are below the LOQ of SPEP.

Are all protein fractions clinically relevant to multiple myeloma?

No. Aside from gamma immunoglobins, the other protein fractions are not clinically relevant to multiple myeloma. 

There may be instances where providers such as primary care, nephrologists, internal medicine, and others may have been ordering the protein electrophoresis to determine albumin, alpha-1, alpha-2, and beta protein levels for non-multiple myeloma-related disease purposes. In these instances, the tests below should be ordered instead:

Can MASS-FIX testing be used to monitor patients on therapies other than daratumumab? 

Yes, MASS-FIX testing currently is validated for several therapies. At the time of ordering QMPSS for monitoring, include the name of the monoclonal therapy that the patient is on in a note in the comment section of the test. The monoclonal therapies that the testing will be able to detect is expanding. If a peak with an isotype matches a drug in our detection tables, it will be reported as consistent with that drug. In situations where two peaks (one monoclonal and one drug) are identified, the report will reflect individual quant values of both peaks and labeled accordingly.

Can this test be used to replace MRD testing on a bone marrow sample? 

While this testing does not replace MRD monitoring by bone marrow, several studies have shown an increase in disease-free survival when both the bone marrow and MASS-FIX tests are negative. 

Is there published clinical data that highlights the use of MASS-FIX to detect minimal residual disease (MRD) in multiple myeloma? For example, can MASS-FIX be used when a healthcare provider is considering stopping therapy? 

The use of any MRD method to guide the decision to stop treatment is controversial. Mayo Clinic has added MASS-FIX detection and quantitation to bone marrow samples, which adds to the overall predictability of the outcome for the patient. We view early detection as key and having lower level of detection with QMPSS has been useful to identify some diseases that were not evident before, including increased awareness of patients at risk for AL amyloidosis before the onset of symptoms.

Is MASS-FIX testing included in International Myeloma Working Group testing recommendations?

Yes. Due to improvements made by MASS-FIX, Mayo Clinic permanently replaced gel immunofixation and protein electrophoresis analysis.

Is there data that compares daratumumab in an electrophoretic mobility shift assay and MASS-FIX? 

Because the MASS-FIX assay has been available at Mayo Clinic for several years, we have never utilized the shift assay at Mayo Clinic and do not have a published comparison.

Won’t this test methodology simply find more patients with MGUS who will need to be monitored? 

In a recent publication, Mayo Clinic determined that there was a minimal increase in the number of MGUS patients identified with this methodology. However, with the enhanced ability of this testing to track glycosylated light chains and quantitate, this test provides a deeper level of understanding and identification of patients who are at a higher risk of transitioning to multiple myeloma or AL amyloidosis. 

Highlights


References
  1. Dispenzieri A, Krishnan A, Arendt B, et al. Mass-Fix better predicts for PFS and OS than standard methods among multiple myeloma patients participating on the STAMINA trial (BMT CTN 0702 /07LT). Blood Cancer J. 2022;12(2):27. Published 2022 Feb 10. https://pubmed.ncbi.nlm.nih.gov/35145071/
  2. Derman BA, Stefka AT, Jiang K, et al. Measurable residual disease assessed by mass spectrometry in peripheral blood in multiple myeloma in a phase II trial of carfilzomib, lenalidomide, dexamethasone and autologous stem cell transplantation. Blood Cancer J. 2021;11(2):19. Published 2021 Feb 5. doi:10.1038/s41408-021-00418-2 https://pubmed.ncbi.nlm.nih.gov/33563912/
  3. Puig N, Contreras MT, Agulló C, et al. Mass spectrometry vs immunofixation for treatment monitoring in multiple myeloma. Blood Adv. 2022;6(11):3234-3239. doi:10.1182/bloodadvances.2021006762 https://pubmed.ncbi.nlm.nih.gov/35157768/
  4. Milani P, Murray DL, Barnidge DR, et al. The utility of MASS-FIX to detect and monitor monoclonal proteins in the clinic. Am J Hematol. 2017;92(8):772-779. doi:10.1002/ajh.24772 
  5. Mills JR, Kohlhagen MC, Willrich MAV, Kourelis T, Dispenzieri A, Murray DL. A universal solution for eliminating false positives in myeloma due to therapeutic monoclonal antibody interference. Blood. 2018;132(6):670-672. doi:10.1182/blood-2018-05-848986
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