Mass Spectrometry Versus Immunofixation to Monitor Multiple Myeloma Treatment

The monoclonal protein (M-protein), secreted by the tumor plasma cells in patients with multiple myeloma (MM), has long been used as a biomarker to evaluate treatment response. Treatment monitoring in MM is mainly based on the identification and quantification of the M-protein by electrophoresis and/or immunofixation (IFE) in serum and urine samples.

Although the clinical value of these methods has been broadly demonstrated, the current use of highly active therapies has significantly increased the proportion of patients in whom the M-protein becomes undetectable by IFE during and after treatment. There is an urgent need to adjust the sensitivity of the techniques used for response assessment to the current treatment efficacy.

A large team of Hematologists at the Centro de Investigación Biomédica en Red de Cáncer (CIBERONC, Madrid, Spain) and their colleagues included the first 223 out of the 458 newly diagnosed transplant-eligible patients with MM enrolled the PETHEMA/GEM2012MENOS65 trial. This open-label, phase 3 trial encompassed the administration of six induction cycles of bortezomib, lenalidomide, and dexamethasone and autologous stem-cell transplantation (ASCT) followed by two consolidation cycles of bortezomib, lenalidomide, and dexamethasone.

The presence of an M-protein in serum was assessed in parallel by IFE on the Hydrasys 2 instrument using the Hydragel 9 kit (Sebia Inc, Norcross, GA. USA) and by Mass Spectrometry (MS) using the EXENT system (The Binding Site; Birmingham, UK). Pooled normal serum was used as a negative control. The EXENT-iP500 liquid handler purified the immunoglobulins through paramagnetic beads coated with polyclonal sheep antibodies specific for human immunoglobulins. Then, analysis with the EXENT-iX500 matrix-assisted laser desorption/ionization-time of flight device was carried out, and mass spectra from 5,000 to 32,000 mass-to-charge ratio were collected.

The investigators reported that at baseline, the isotypes identified with both methods fully matched in 82.1% of samples. In the rest but for two cases, EXENT&FLC-MS provided additional information to IFE with regards to the M-protein(s). Overall, the results of EXENT&FLC-MS and IFE were concordant in more than 80% of cases, being most discordances due to EXENT&FLC-MS positive, but IFE negative cases. After consolidation, IFE was not able to discriminate two cohorts with different median progression-free survival (PFS), but EXENT&FLC-MS did so. Furthermore, among IFE negative patients, EXENT&FLC-MS identified two groups with significantly different median PFS.

The authors concluded that compared with IFE, EXENT&FLC-MS is more sensitive to detect the M-protein of patients with MM, both at baseline and during treatment, and provides a more accurate prediction of patients’ outcome. The study was published on May 31, 2022 in the journal Blood Advances.

Related Links:
Centro de Investigación Biomédica en Red de Cáncer
Sebia
The Binding Site