What Does AL Amyloidosis Look like in the Era of Mass Spectrometry Typing

Abstract Background: Amyloidosis can stem from various amyloid types. Accurate amyloid typing is crucial for management and prognostic purposes. Typing used to rely on immunohistochemistry and immunofluorescence methods, but is subject to considerable false positive and false negative results as well as dependence on laboratory expertise. Mass spectrometry (MS) has emerged in the past years as the gold-standard typing method with sensitivity and specificity approaching 100%. It is helpful in elimination of cases where monoclonal protein studies are an incidental finding, while amyloidosis type is in fact non-AL. With this technique in clinical practice for nearly a decade, accurate description of AL amyloidosis from a clinical and laboratory data is now feasible, which allows a refinement of the presenting features of the disease compared to prior cohort descriptions. Methods: Five hundred and ninety two patients with biopsy-proven, MS confirmed AL amyloidosis diagnosed between 2008 to 2015 are included. Monoclonal protein studies were performed at diagnosis before treatment initiation and included: serum immunofixation (IFE), urine IFE and serum free light chain assay (sFLC). Comparison was made with data from prior study pre-MS era from our institution: (Gertz MA, Kyle RA. (1989) Primary systemic amyloidosis: a diagnostic primer, Mayo Clinic Proceedings). Results: A lambda clone was seen in 75% of patients in the MS-verified cohort, compared to 62% in the prior study. The rate of detection of a monoclonal protein by serum or urine IFE was 94%, as compared to 86% previously (Figure). The distribution of monoclonal proteins also differed with more patients in the earlier cohort with an IgG kappa and fewer without an intact immunoglobulin. Abnormal sFLC ratio (>1.65 or 3.3 or Conclusion: When mass spectrometry is used to definitively type amyloid and state of the art serum and urine immunofixation and serum free light chain analysis are used, only a fraction of a percent of AL patients have negative monoclonal protein studies, unlike historical reports. Whether this is due to a drift in the prevalence of monoclonal proteins over time or a reflection of misclassification in an era with limited diagnostic capability will require further study. Download : Download high-res image (89KB) Download : Download full-size image Figure . Disclosures Gertz: Millennium: Consultancy, Honoraria; Celgene, Novartis, Smith-Kline, Prothena, Ionis, Amgen: Honoraria. Dingli: Millenium: Consultancy; Alexion Pharmaceuticals: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Karyopharm Therapeutics: Research Funding. Kapoor: Takeda, Celgene and Amgen: Research Funding. Russell: Vyriad: Equity Ownership; Imanis Life Sciences: Equity Ownership. Kumar: Celgene, Millennium, BMS, Onyx, Janssen, Noxxon, AbbVie, Amgen, Merck, Oncopeptides, Skyline Diagnostics, Takeda: Consultancy; Celgene, Millennium/Takeda, Onyx, AbbVie, Janssen, Sanofi, Novartis, Amgen, Genentech, Merck, Oncopeptides, Roche, Skyline Diagnostics: Research Funding; Skyline: Honoraria. Dispenzieri: Celgene, Millenium, Pfizer, Janssen: Research Funding.