Improved Survival in AL Amyloidosis: A Population-Based Study on 1,430 Patients Diagnosed in Sweden 1995-2013
Authors: Weiss Brendan M. , Lund Sigrun H , Bjorkholm Magnus , Cohen Adam D. , Dember Laura , Landgren Ola , Kristinsson Sigurdur Y 
Published: October 2019

Abstract
Introduction: AL amyloidosis (AL) is a plasma cell disorder characterized by life-threatening vital organ dysfunction resulting in nearly a third of patients dying within the first year of diagnosis. The only available therapies are anti-plasma cell chemotherapy agents, which reduce the toxic and amyloidogenic immunoglobulin light chains. We have previously shown improved survival in multiple myeloma (MM) due to novel anti-plasma cell therapies. Studies from specialty amyloid centers have also shown improved survival in AL, but this has never been studied in a population-based setting.
Methods: By using the nationwide Swedish Patient Registry we identified all individuals registered with AL amyloidosis (defined as more than one occurrence of the ICD-code E85.8 and E85.9) in Sweden 1995-2013. By using the Total Population Registry we identified four matched controls for each case of amyloidosis, matched by gender and year of birth, and the controls had to be alive at the time of diagnosis for the corresponding AL-amyloidosis case. By using the Cause of Death Registry we obtained information on date of death, with follow-up through 2013. Overall survival (OS) was analyzed using Kaplan-Meier method and Cox proportional model, adjusting for age, gender, and calendar period of diagnosis. The cohort was divided into 4 calendar periods to evaluate changes in overall survival (OS) over time.
Results: We identified 1,430 AL patients; mean age at diagnosis of 66.3 years; male gender 58.5%. A diagnosis of MM was made in 10.7% of patients, 3.6% after the AL diagnosis (AL-MM) and 7.1% before the AL diagnosis (MM-AL). Compared to matched controls, AL patients in the entire cohort had a median OS of 1.72 years, median OS was not reached for controls (p<0.001). The median OS of MM-AL was 0.51 years, AL-MM 0.88 years and AL 1.87 years (p<0.001). Median OS for AL patients improved significantly over time: 0.77 years for 1995-99, 1.37 years for 2000-04, 1.85 years for 2005-09, and 3.48 years for 2010-2013 (p for trend <0.001). Survival improvements over time were observed in both those younger and older than age 65. The 1-year survival for AL patients was: 43% for 1995-1999, 58% for 2000-2004, 59% for 2005-2009 and 70% 2010-2013 (p<0.001). The 2-year survival rates: 30% for 1995-1999, 42% for 2000-2004, 49% for 2005-2009 and 61% 2010-2013 (p<0.05).
Conclusions: In the first population-based study of outcomes in AL, based on almost 1,500 patients diagnosed during almost 20 years, we found that OS has improved over time. The most probable explanation is the availability of highly-effective anti-plasma cell agents and possibly improvement in supportive care. We have also demonstrated an improvement in early mortality in AL amyloidosis possibly due to earlier recognition of disease and prompt anti-plasma cell chemotherapy. This novel finding deserves further investigation.
Figure 1 Figure 1.

Disclosures
Weiss: Prothena: Other: Travel, accommodations, Research Funding; GlaxoSmithKline: Consultancy; Millennium: Consultancy, Other: Travel, accommodations; Janssen: Consultancy, Other: Travel, accommodations, Research Funding; Novartis: Consultancy. Cohen:Bristol-Meyers Squibb: Consultancy, Research Funding; Janssen: Consultancy. Landgren:Amgen: Honoraria, Research Funding; BMS: Honoraria; Celgene: Honoraria, Research Funding; Takeda: Honoraria; Merck: Honoraria; Medscape Myeloma Program: Honoraria.