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

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.AL = primary systemic amyloidosis; CI = confidence interval; cTnT = cardiac troponin T; NT-proBNP = N-terminal pro-brain natriuretic peptide; OS = overall survival; SCT = stem cell transplantPrimary systemic, or light-chain, amyloidosis (AL) is a clonal plasma cell disorder characterized by a relatively low plasma cell burden and multiorgan deposition of immunoglobulin light-chain–derived amyloid fibrils.^1-5 Although amyloid fibrils can originate from more than 25 different proteins, AL is the most common form of amyloidosis. The survival of patients with amyloidosis is quite variable, with median survival ranging from 12 to 18 months in different series, and largely depends on the number of organs involved and the severity of their involvement.^1,2,6 High-dose therapy and stem cell transplant (SCT) have been increasingly used for treatment of this disease, and case-control studies suggest an improved outcome, although this modality is an option only for a minority of patients.^6-11 Treatment of amyloidosis has typically followed developments in therapy for multiple myeloma, in which a marked shift in treatment approaches has occurred because of the availability of several effective new drugs in the past 10 years.¹² These changes have improved survival in patients with myeloma during the past decade.¹³ In addition to new drugs, the combination of melphalan and dexamethasone is an effective regimen for AL, and risk-adapted approaches to SCT have decreased treatment-related mortality.^14-24 Whether recent progress in risk stratification and treatment approaches has translated into improved survival for these patients is unclear. Therefore, we undertook this study to examine trends in survival of patients with AL over time, with an emphasis on identifying patient characteristics predicting outcome.