Higher Plasma Cell Burden Predicts for Early Death In Patients with AL Amyloidosis

Abstract

AbstractAbstract 1893 Background:Recent data has shown that the level of immunoglobulin free light chain (FLC) is a prognostic factor for patients with AL amyloidosis. Approximately 25% of patients with AL amyloidosis have coexistent multiple myeloma (MM) with myeloma-related end-organ damage and patients may also present with 310% plasma cells (PC) in the bone marrow (BM) in the absence of any MM features. The goal of this study was to determine the effect of increased BM plasmacytosis in the absence of MM end-organ damage on early mortality. Methods:We performed a retrospective study of 263 consecutive patients with AL amyloidosis seen at Mayo Clinic within 30 days of diagnosis from July 2002 – April 2009, to compare the effect of PC burden among those who died within 90 days of diagnosis (n=88) and those who survived more than 90 days after diagnosis (n=175). Only those patients with documented BM PC were included in this study. MM end-organ damage was defined according to the CRAB criteria. Results:In those who died <90 days after diagnosis and patients who lived beyond 90 days, the proportion of patients with 310% BM PC were 57% and 55%, respectively. Overall survival (OS) was significantly shorter in the early mortality group when there was 310% BM PC present at diagnosis (25 vs. 54 days, p=0.006), but this was not observed in the group who survived beyond 90 days (Figure 1). In patients with 310% BM PC, troponin-T, ejection fraction (EF), and hemoglobin (Hgb) were significantly worse in the early mortality cohort but patients who survived beyond 90 days had significant increase in intraventricular septal (IVS) thickness and beta-2 microglobulin (Table 1). As expected, patients with 310% BM PC in both cohorts had significantly higher serum M-spike and involved FLC (Table). The same cohort of patients were analyzed substituting MM-related end-organ damage for 310% BM PC and similar results were observed with the exception of uric acid and calcium being significantly higher in the early mortality cohort with MM (results not shown). Conclusion:This study demonstrated that an excess of early—but not late—deaths occur in AL amyloidosis patients with 310% BM PC at diagnosis. In our cohort, this finding can be attributed to higher troponin-T levels, indicating more severe cardiac involvement as observed by worse cardiac function. These findings warrant additional investigation. [Display omitted] Table 1:Variables (median) analyzed in patients who died within 90 days or survived beyond 90 days of diagnosis of AL amyloidosis based on their BM PC%VariableDied within 90 days of diagnosisSurvived beyond 90 days of diagnosisBM PC <10% (n = 38)BM PC 310% (n = 50)p-valueBM PC <10% (n = 79)BM PC 310% (n = 96)p-valueHemoglobin, g/dl13.612.60.0113.413.10.55Serum M-spike, g/dl000.020.51.20.04Beta-2 microglobulin, mcg/ml3.44.60.172.613.160.01Troponin-T, ng/ml0.070.140.010.010.010.30NT-proBNP, pg/ml564493600.09132512610.46EF, %55.5450.0264640.74IVS, mm14150.211213.50.01PCLI, %00.20.1700.10.001BM PC, %520<0.0001516.5<0.0001Involved FLC, mg/dl23.286.9<0.000113.531.10.0004Lambda- restricted patients, %34.137.50.9431.037.40.56 Disclosures:Lacy:Celgene: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria.