Glomerular Fitration Rate and Lactate Dehydrogenase Predicts Survival in Mayo Iiib Stage Light-Chain Amyloidosis

Background: Systemic light chain amyloidosis is a protein misfolding disease caused by a clonal plasma cell in the bone marrow, which results in organ failure due to deposition of misfolded light chains in affected organs. In clinical routine, the modified Mayo Classification of 2004 is broadly established and is further used to guide therapy.Patients in the most advanced stage IIIB have a very poor prognosis with a 2-year survival around 30%. In the present study, we investigate additional risk factors that may predict survival in Mayo stage IIIB patients.

Objective: To study the impact of pretreatment levels of GFR and LDH on survival in patients with Mayo Stage IIIB AL amyloidosis.

Material & Methods: Data were collected from 35 patients presented between 2015 and 2021 in our department of Hematology and Stem Cell Transplantation. We assessed cut-off values for GFR and LDH using simple logistic regression and ROC-analysis. Kaplan-Meyer-Survival analysis and Cox regression hazard model were applied to assess the hazard ratios. The used statistical software was GraphPad PRISM, version 9.3.1.

Results: The study included 35 patients with histologically confirmed diagnosis of AL amyloidosis and cardiac involvement in stage IIIb regarding Mayo classification 2004. Patients were divided into 3 groups/stages after assessing cut-off values for LDH and GFR, which significantly negatively affected survival (group 1: n = 7, LDH < 294 U/L, GFR ≥45 ml/min/1.73m²; group 3: n = 14, LDH ≥ 294 U/L, GFR <45 ml/min/1.73m²and group 2: n = 14, neither 1 nor 3). Our data show a significantly negative outcome with increasing levels of LDH and decreasing levels of GFR (Log-rank test, p = 0.02) and a median overall survival of 2 months in group 3 und 6 months in group 2. Performing a univariate cox regression model showed that the risk of death in group 3 is increased 4.5 times compared to group 1 (HR =4.5, 95%CI 1.42 to 20.13, p = 0.02)and 2.3 times compared to group 2 (HR = 2.3, 95%CI 0.976 to 5.907, p = 0.06),whereas no significant increase in risk of death was found in group 2 compared to group 1 (HR = 1.9, 95%CI 0.55to 8.97, p = 0.3).

Summary & Conclusion: GFR and LDH are suitable prognostic parameters to predict survival of in Mayo Stage IIIB AL amyloidosis. LDH ≥294 U/L in combination GFR < 45 ml/min/1.73m²in patients with Mayo IIIB predicts poor outcome with an overall survival of less than 10% in 12 months after diagnosis of the disease. Studies with cohorts from other centers to confirm the data are needed; furthermore, the causes of treatment failure should be investigated depending on the newly defined risk factors in a larger cohort.

Carpinteiro:Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Amgen: Membership on an entity's Board of Directors or advisory committees. Reinhardt:Gilead: Research Funding; Abbvie: Honoraria; Merck: Honoraria; CDL Therapeutics GmbH: Other.