Detection of M-protein by iMS-IP and iMS-FLC assays redefines previously non-secretory POEMS syndrome

OBJECTIVES: In polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome, when monoclonal plasma cell proliferation is absent, it is considered 'non-secretory POEMS syndrome'. We aimed to study whether M-protein was detectable by mass spectrometry (MS) in previously non-secretory POEMS syndrome. METHODS: M-protein was analyzed using intact mass spectrometry-immunoprecipitation (iMS-IP) and iMS-FLC Assays on the baseline serum samples of patients with 'previously non-secretory POEMS' syndrome (n=21) and from patients undergoing treatment follow-up (n=17). RESULTS: Out of 21 previously non-secretory POEMS patients, 20 (95 %) had M-protein by MS at presentation. The types of M-protein in previously non-secretory POEMS patients were: IgA λ (35 %), free λ (25 %), IgD λ (20 %), IgG λ (15 %), and biclonal (IgA λ and IgM λ) (5 %). During treatment follow-up, the overall response rate of serum vascular endothelial growth factor (VEGF) was 100 %, and the median time to VEGF response was 3 months. In contrast, during and after treatment, only 6 out of 16 patients (37 %) achieved M-protein negativity by MS (median time of 9 months). CONCLUSIONS: MS-assisted M-protein detection could achieve accurate diagnosis for many patients with 'previously non-secretory POEMS', and may prove useful for tracking treatment outcomes in individuals with MS-positive baseline M-protein.