Recent improvements in survival in primary systemic amyloidosis and the importance of an early mortality risk score

Abstract

Objective: To examine whether the outcome of patients with primary systemic amyloidosis (AL) has improved over time and to identify predictors of early mortality in patients with AL.

Patients and methods: We studied 2 separate cohorts of patients. The first cohort, consisting of 1998 patients with AL seen at Mayo Clinic between January 1977 and August 2006, was used to examine the trends in overall survival (OS) from diagnosis during this 30-year period. The second cohort, consisting of 313 patients seen between September 2006 and August 2009, was used to validate a model for predicting early mortality.

Results: The 4-year OS from diagnosis improved during each decade of follow-up: 21%, 24%, and 33%, respectively, for the periods 1977-1986, 1987-1996, and 1997-2006 (P<.001). Within the last group (1997-2006), 4-year OS during 1997-1999, 2000-2002, and 2003-2006 was 28%, 30%, and 42%, respectively (P=.02). However, the 1-year mortality remained high during the 30-year period. A risk stratification score using cardiac troponin T, N-terminal probrain natriuretic peptide, and uric acid identified patients at risk of early mortality. The 1-year mortality with 0, 1, 2, or 3 risk factors was 19%, 37%, 61%, and 80%, respectively, in this training cohort of 459 patients. This was confirmed in a validation cohort of 313 patients.

Conclusion: Survival in AL has improved over time, with maximum improvement occurring in the past decade. However, early mortality remains high, and prospective identification of patients at risk of early mortality may allow development of risk-adapted strategies.

FIGURE 1.

A, Overall survival (OS) from diagnosis among 1998 patients with primary systemic amyloidosis (AL), divided into 3 cohorts on the basis of date of diagnosis: 1977-1986 (n=345), 1987-1996 (n=636), and 1997-2006 (n=1017). The median OS from diagnosis for the 3 groups was 1.2, 1.2, and 1.5 years, respectively. The 4-year survival estimates for the 3 groups were 21%, 24%, and 33%, respectively (P<.001). B, Overall survival from diagnosis among patients with AL diagnosed during three 10-year periods, excluding those who received stem cell transplant at any time during the course of the disease. This group included 1791 patients: 1977-1986 (n=303), 1987-1996 (n=585), and 1997-2006 (n=903). Median OS for the 3 groups was 1.2, 1.2, and 1.4 years, respectively (P<.001). C, Overall survival from diagnosis among patients with AL diagnosed during 1997-2006 (n=1017), divided into 3 groups according to date of diagnosis: 1997-1999 (n=263), 2000-2002 (n=291), and 2003-2006 (n=463). The 4-year OS from diagnosis for the 3 groups was 28%, 30%, and 42%, respectively (P=.02).

FIGURE 2.

Upper left: Overall survival (OS) from diagnosis among 491 patients with available laboratory data, grouped according to the cardiac troponin T (cTnT) and n-terminal pro-brain natriuretic peptide (NT-proBNP) staging system. The staging system uses a cutoff value for NT-proBNP of less than 332 ng/l and a cutoff value for cTnT of less than 0.035 μg/L. Depending on whether values were both low, high for only one, or high for both, patients were classified as having stage I, II, or III disease, respectively. the median Os from diagnosis for patients in stages I, II, and III was 4.0, 2.4, and 0.5 years, respectively (P<.001). Upper Right, Lower Left, Lower Right: Overall survival from diagnosis among patients in prognostic stages I, II, and III, respectively, with each stage divided into 3 groups according to the date of diagnosis (group A, 1987-1996; group B, 1996-2004; and group C, 2004-2006). Among patients with stage I disease, the median OS was not reached for group B or C and was 2.3 years (95% confidence interval, 1.4-3.3) for group A (upper right). Among patients with stage II disease, the median OS was not reached for the recent group and was 2.4 years for group B and 0.9 year for group A (lower left). Finally, among stage III patients, the most recent group had a median OS of 1.0 year compared with 0.4 year for both group A and group B (P<.001; lower right).

FIGURE 3.

A, One-year mortality rates among patients with 0, 1, 2, or 3 risk factors for early mortality. The 3 risk factors were cardiac troponin T level greater than 0.01 μg/L, N-terminal pro-brain natriuretic peptide level greater than 4200 ng/L, and uric acid greater than 8.0 mg/dL. Patients with data available for all 3 variables (n=459) were included in this analysis. The probability of dying within 1 year for those with 0, 1, 2, and 3 risk factors was 19%, 37%, 61%, and 80%, respectively (P<.001). B, One-year mortality rates among patients with 0, 1, 2, or 3 risk factors for early mortality from among patients seen during 2006-2009. Patients with data available for all 3 variables (n=313) were included in this analysis. The probability of dying within 1 year for those with 0, 1, 2, and 3 risk factors was 12%, 24%, 46%, and 69%, respectively (P<.001).