Detection of Plasma Cell Disorders by Mass Spectrometry: A Comprehensive Review of 19,523 Cases

Surendra Dasari, Mindy C. Kohlhagen, Angela Dispenzieri, Maria A.V. Willrich, Melissa R. Snyder, Taxiarchis V. Kourelis, John A. Lust, John R. Mills, Robert A. Kyle, David L. Murray

Research output: Contribution to journalArticlepeer-review


Objectives: To verify the analytical performance of a new mass spectrometry–based method, termed MASS-FIX, when screening for plasma cell disorders in a routine clinical laboratory. Patients and Methods: Results from 19,523 unique patients tested for an M-protein between July 24, 2018, and March 6, 2020, by a combination serum protein electrophoresis (SPEP) and MASS-FIX were examined for consistency with pretest implementation performance. MASS-FIX's ability to verify abnormal results from SPEP and free light chain measurements was then compared with that of immunofixation electrophoresis (IFE) using a separate cohort of 52,586 patients tested by SPEP/IFE during the same period. Results: Overall, 62.4% of our cohort was negative for an M-protein. Importantly, 7.3% of all specimens had an M spike on SPEP (0.1 to 8.5 g/dL) and MASS-FIX detected an M-protein in all these samples. Of all samples, 30.3% had M-proteins that were detected by MASS-FIX but the SPEP finding was too small for quantification. Of the positive samples, 5.7% contained a therapeutic monoclonal antibody. Of the positive samples, 4.1% had an N-glycosylated light chain (biomarker of high-risk plasma cell disorders). MASS-FIX confirmed a higher percentage of SPEP abnormalities than IFE. MASS-FIX was slightly more sensitive than IFE when confirming an M-protein in samples with an abnormal free light chain ratio. MASS-FIX had a very low sample repeat rate (1.5%). MASS-FIX was highly automatable resulting in a higher number of samples/technologist/day than IFE (∼30% more). Conclusion: Overall, MASS-FIX was successful in maintaining validation characteristics. MASS-FIX was more sensitive in confirming SPEP abnormalities when compared with IFE. Ability to detect therapeutic monoclonal antibodies and glycosylated light chains was distinctly advantageous.

Original languageEnglish (US)
Pages (from-to)294-307
Number of pages14
JournalMayo Clinic proceedings
Issue number2
StatePublished - Feb 2022

ASJC Scopus subject areas

  • Medicine(all)


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