Introduction: Light chain amyloidosis (AL) is a progressive, multisystemic disease caused by the buildup of misfolded immunoglobulin light chains. Tafamidis, the first FDA-approved amyloidosis therapy for transthyretin cardiac amyloidosis in 2019, sparked an increased awareness of amyloid-related cardiomyopathies, including AL amyloidosis. In 2021, with daratumumab as the first FDA-approved therapy specific to AL amyloidosis, further disease-specific AL amyloidosis awareness and education increased. Evaluation of the impact of increased disease awareness using real-world data from patients on symptom onset and diagnostic journey are needed. The purpose of this study is to evaluate trends in diagnostic delay and initial symptom presentation among newly diagnosed AL amyloidosis patients from 2022-2024.

Methods: The Amyloidosis Research Consortium (ARC) conducted annual cross-sectional online surveys of patients with a self-reported diagnosis of amyloidosis in 2022-2024. Survey measures included demographics, date of initial symptom onset and diagnosis, initial/early symptoms, and diagnostic barriers. Respondents with a self-reported diagnosis of AL amyloidosis within 18 months of survey administration were defined as newly diagnosed and included in this analysis. Comparisons across survey years were made using chi-squared tests and Wilcoxon rank sum tests.

Results: Of 1,171 respondents with AL amyloidosis, 164 were recently diagnosed in 2022 (N=58), 2023 (N=53), and 2024 (N=53). Demographic and disease characteristics were similar during the three survey years. The average age was 66 years in 2022 and 65 in both 2023 and 2024. Most patients lived in the United States, 69% in 2022 and 85% and 83% in 2023 and 2024, respectively. Heart involvement was reported in 69% in 2022, and 62% and 60% in 2023 and 2024, respectively. Kidney involvement was also reported in 55% of AL patients in 2022, and 64% and 62% in 2023 and 2024, respectively. The time (mean [standard deviation]) from initial symptoms pre-diagnosis to diagnosis of amyloidosis went from 2.7 (4.9) in 2022, 1.7 (2.4) in 2023, and 1.4 (2.3) years in 2024 (p=0.005). Symptoms pre-diagnosis were predominantly cardiac in nature. Overall, 78% of patients reported cardiac symptoms first, rising from 67% in 2022 to 85% in 2024 (p = 0.05). Peripheral neuropathy early symptoms slightly increased from 33% (2022) to 40% (2023) to 55% (2024) (p=0.060). The proportion of patients reporting autonomic symptoms pre-diagnosis increased from 40% in 2022, to 25% in 2023, up to 57% in 2024 (p=0.004). Other early symptoms increased significantly in 2024 from 41% (2022) and 29% (2023) to 68% in 2024 (p<0.001). The mean number of physicians seen prior to diagnosis remained consistent across the survey years, 3.3 (2022), 3.5 (2023), and 3.4 (2024) (p=0.7). Hematologist/oncologists provided the diagnosis in 41% of patients in 2022, and 32% and 34% of patients in 2023 and 2024, respectively. Rates of reported fat pad or bone marrow biopsies remain consistent; the proportion of patients with fat pad biopsies as part of their diagnostic workup was 29% in 2022, 23% in 2023, and 34% in 2024 (p=0.4) and the proportion of patients with bone marrow biopsies was 71% (2022), 68% (2023), and 77% (2024) (p=0.5). More than half of patients reported diagnostic barriers—52% (2022), 53% (2023) and 71% (2024) (p=0.07)—most commonly being misdiagnosed or given alternative diagnoses [24% (2022), 28% (2023), and 32% (2024) (p=0.7)] and convincing the doctor that symptoms are real [21% (2022), 25% (2023), and 34% (2024) (p=0.3)]. While approximately 10% of patients were still awaiting treatment [11% (2022), 8% (2023), and 11% (2024)], more initiate their treatment within a week of diagnosis [13% (2022), 20% (2023), and 21% (2024)], and most receive their first treatment within a month of diagnosis [52% (2022), 69% (2023), and 70% (2024) (p=0.6)].

Conclusion: Patients with AL amyloidosis recently diagnosed from 2022-2024 experienced shorter diagnostic delays but continue to see multiple physicians prior to diagnosis and initiating treatment. This may suggest once patients are in the health care system physicians can quickly diagnose, but the multi-step referral process may continue to contribute to delays. The shift in symptom profiles suggests a rising disease awareness and better screening allowing patients to receive treatment faster.

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2025
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