Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements

Abstract

Purpose: Cardiac involvement predicts poor prognosis in light chain (AL) amyloidosis, and the current prognostic classification is based on cardiac biomarkers troponin-T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-ProBNP). However, long-term outcome is dependent on the underlying plasma cell clone, and incorporation of clonal characteristics may allow for better risk stratification.

Patients and methods: We developed a prognostic model based on 810 patients with newly diagnosed AL amyloidosis, which was further examined in two other datasets: 303 patients undergoing stem-cell transplantation, and 103 patients enrolled onto different clinical trials.

Results: We examined the prognostic value of plasma cell-related characteristics (ie, difference between involved and uninvolved light chain [FLC-diff], marrow plasma cell percentage, circulating plasma cells, plasma cell labeling index, and β(2) microglobulin). In a multivariate model that included these characteristics as well as cTnT and NT-ProBNP, only FLC-diff, cTnT, and NT-ProBNP were independently prognostic for overall survival (OS). Patients were assigned a score of 1 for each of FLC-diff ≥ 18 mg/dL, cTnT ≥ 0.025 ng/mL, and NT-ProBNP ≥ 1,800 pg/mL, creating stages I to IV with scores of 0 to 3 points, respectively. The proportions of patients with stages I, II, III and IV disease were 189 (25%), 206 (27%), 186 (25%) and 177 (23%), and their median OS from diagnosis was 94.1, 40.3, 14, and 5.8 months, respectively (P < .001). This classification system was validated in the other datasets.

Conclusion: Incorporation of serum FLC-diff into the current staging system improves risk stratification for patients with AL amyloidosis and will help develop risk-adapted therapies for AL amyloidosis.

Fig 1.

(A) Kaplan-Meier curves for overall survival (OS) from diagnosis among 758 patients based on the new staging system; shaded areas indicate the 95% CI estimates. (B) Kaplan-Meier curves for OS from diagnosis among 512 patients based on the staging system, substituting B-type natriuretic peptide for N-terminal pro–B-type natriuretic peptide. (A, B) Patients surviving beyond 5 years were censored at the 5-year mark. Numbers of patients at risk at each time point are shown below the x-axis. Survival curves were compared using log-rank test.

Fig 2.

(A) Kaplan-Meier curves for overall survival (OS) from diagnosis among the subgroup of 583 patients based on the new staging system. Patients surviving beyond 5 years were censored at the 5-year mark. (B) Kaplan-Meier curves for OS from stem-cell transplantation among 303 patients based on the new staging system. Patients surviving beyond 4 years were censored at the 4-year mark. (C) Kaplan-Meier curves for OS from time of trial entry among 103 patients enrolled onto different trials based on the new staging system. Patients surviving beyond 4 years were censored at the 4-year mark. (A, B, C) Numbers of patients at risk at each time point are shown below the x-axis. Survival curves were compared using log-rank test.