Light-Chain Amyloidosis in Sweden (2011-2019): Incidence, Disease Burden, and Clinical Outcomes in Real-World Patients

Introduction: Light-chain (AL) amyloidosis is a rare plasma cell disorder characterized by organ damage caused by deposits of light-chain amyloid fibrils. While prior research indicates that outcomes for AL patients have improved with the adoption of novel anti-plasma cell combination therapies as standard of care, there are limited population-based data characterizing outcomes in contemporary real-world patients with AL. In the present study, Swedish registry data were used to characterize AL incidence trends, patient clinical characteristics, and outcomes in real-world patients newly diagnosed with AL.

Methods: Data came from six nationwide population-based registers provided by the National Board of Health and Welfare in Sweden and Statistics Sweden and linked by unique personal identity number. Patients ≥18 years of age and newly diagnosed with AL were identified on the basis of having ≥2 diagnosis codes for amyloidosis (ICD-10-SE codes E85.4x, E.85.8x, E85.9) from 1/1/2011 to 12/31/2019 plus ≥1 of the following: (1) receipt of anti-plasma cell therapy, (2) an amyloidosis diagnosis made in a hematology/oncology clinic, and/or (3) a diagnosis code specific to AL (E85.8A). Patients with a prior history of amyloidosis or specific diagnosis codes or treatments consistent with non-AL amyloidosis etiologies were excluded. For each newly diagnosed AL case, individuals from the general population without any type of amyloidosis were randomly selected and matched with a maximum ratio of 1:5 based on age, sex, calendar year, and county. Key measures of interest included AL incidence and prevalence, baseline patient characteristics, burden of and interventional procedures for cardiac and renal complications, and OS overall and by major organ involvement. Risks of incident cardiac and renal failure and OS were quantified with the Kaplan-Meier (KM) estimator; log-rank tests were used to evaluate the differences in survival and Cox regression was used to provide an estimate of the hazard ratio (HR). Patients were followed until date of death or the database cut-off date (12/31/2019), whichever occurred first.

Results: 846 Swedish patients newly diagnosed with AL (median age 70yr, 41% female) and 4,227 demographically matched controls were identified. During the study period, there was an increase in the incidence of AL from 10.5 cases per million in 2011 to 15.1 cases per million in 2019 (test for trend: p<0.001; Figure 1A). At initial diagnosis, 48%, 33%, and 18% of AL patients had evidence of cardiac, renal, and neurologic involvement, respectively; 10% had a history of multiple myeloma. Relative to the non-AL controls, at baseline AL patients had a significantly higher mean Charlson Comorbidity Score (1.7 vs 0.4; p<0.001) and higher rates of cardiac failure (30% vs 5%; p<0.001) and renal failure (12% vs 2%; p<0.001). In AL patients, the KM estimated risks of incident cardiac and renal failure at 5 years following initial diagnosis were 38% and 28%, respectively. Median OS for AL patients was 4.7 years vs. not reached in non-AL controls (HR: 5.8, 95% CI [5.0, 6.7]; Figure 1B).

Conclusions: In this contemporary cohort of real-world Swedish patients newly diagnosed with AL, the risks of cardiac failure, renal failure, and all-cause mortality were higher relative to the demographically-matched general population comparison group. In addition, a trend toward an increased incidence of AL was observed during the study period (2011-2019). This trend may reflect greater awareness of AL and an increased likelihood of it being diagnosed and treated in the last years of this time-period. Compared to the median OS of 1.7 years previously reported for Swedish patients newly diagnosed with AL in 1995-2013 (Weiss et al, Am Soc of Hematology, 2015), the median OS of 4.7 years observed for patients newly diagnosed with AL in the present study represents a meaningful improvement.

Mellqvist:Janssen: Honoraria; BMS: Honoraria; GSK: Consultancy, Honoraria; Sandoz: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Cai:Johnson & Johnson: Current Employment. Hester:Janssen R&D, LLC/Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Grövdal:Janssen-Cilag AB, Sweden: Current Employment. Börsum:Janssen Pharmaceutical: Consultancy. Rahman:Janssen Pharmaceutica: Consultancy. Ammann:Johnson & Johnson: Current Employment, Current equity holder in publicly-traded company. Hansson:Takeda, Janssen, BMS, ASTRA: Consultancy; Celgene and Janssen: Speakers Bureau.