Frequently Asked Questions: MASS-FIX

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. 

Q: 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 health care providers understand their patients’ risk of progression to multiple myeloma or AL amyloidosis. This level of insight is not possible via traditional testing methods.

Q: How sensitive is this test? Are there differences in the sensitivity of the various diagnostic and therapeutic versions of this testing?

Research has shown that MASS-FIX is 10x more sensitive and specific than immunofixation. While the sensitivity and specificity are the same for any diagnostic or therapeutic version of MASS-FIX testing, the approach varies. For example, the diagnostic test that uses serum protein electrophoresis (SPE) will reflex to the MASS-FIX test when a discrete band is identified. This enable’s understanding of that patient’s M-spike, allowing accurate follow-up testing. The therapeutic test TMOGA will reflex to MASS-FIX testing when a discrete band is not identified to look for lower levels not found by SPE. 

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

Yes, MASS-FIX testing currently is validated for the following therapies: daratumumab, elotuzumab, and isatuximab. 

Q: 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. 

Q: 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 health care provider is considering stopping therapy? 

The use of any MRD method to guide the decision to stop treatment is still controversial. 

Q: When a patient is on tMAb therapies, is there data to show that DMOGA and TMOGA can differentiate between two mAb peaks and the M-protein peak clearly? 

In about 85 percent of cases, the MASS-FIX method will resolve the peaks. To enable optimal interpretation of patient results, it’s important to provide our laboratory with information on what mAb therapy the patient is currently receiving.1,2 

Q: 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.

Q: Won’t this test methodology simply find more patients with a 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, 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. 

Citations

  1. 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;92:772-779. 
  2. Mills JR, Kohlhagen MC, Willrich MAV, et al. A Universal Solution for eliminating false positives in myeloma due to therapeutic monoclonal antibody interference. Blood. 2018;132(6):670-672.