Introduction: Light chain (AL) amyloidosis is a rare multi-systemic disease where abnormal proteins in plasma cells misfold and create amyloid fibrils that can deposit in organs and tissues, where they cause damage and increased risk of mortality. Cardiac involvement is the most important factor in determining AL amyloidosis prognosis as well as the difference in free light chains (dFLC), with a dFLC less than 50 mg/L indicating better prognosis. In most countries, daratumumab in combination with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) is the preferred first-line therapy (FLT) for AL amyloidosis. There is no expert consensus for definitions of relapsed/refractory AL amyloidosis and preferred second-line therapy (SLT). This prospective study examined healthcare professional (HCP) perspectives on treatment and management of newly diagnosed and relapsed/refractory AL amyloidosis patients building on research by Milani, et al (2017).

Methods: The Amyloidosis Research Consortium (ARC) conducted an international cross-sectional online survey from April to July 2025. HCPs who treat AL amyloidosis patients were identified from ARC's database and sent an email with individual links to complete the survey. Members of the International Society of Amyloidosis also received email notifications for study participation. Measures included HCP demographics, practice characteristics, FLT and SLT preferences, clinical trial perspectives, and use of clinical criteria including dFLC values, relapsed/refractory definitions, and hematologic and organ progression. Target enrollment was 50 HCPs. Final enrollment was 55 HCPs with evaluable data from 49 respondents included in analysis. This preliminary analysis examined respondent characteristics, treatment preferences, and clinical trial perspectives; results of the full analysis will be presented in a forthcoming manuscript. Responses were analyzed descriptively using STATA.

Results: Respondents were based in the United States (60%), Europe (30%), Australia (4%), South America (4%), and South Korea (2%). The majority were hematologists or oncologists (85% and 10%, respectively), male (67%), between the ages of 36 and 65 years old (90%), and practice at academic institutions (94%). Most had more than 10 years of experience treating AL amyloidosis patients (80%), with almost half having 20 years or more experience (46%) On average, HCPs treat 100 AL amyloidosis patients per year (mean 63.9, SD 111.1), with 30% newly diagnosed (mean 25.1%, SD 17.8%), 30% observed off therapy (mean 27.0%, SD 13.8%), 18% on maintenance therapy (mean 16.7%, SD 9.7%), and 23% relapsed/refractory (mean 19.8%, SD 10.7%). Half of respondents (50%) use the EU modification of the 2004 Mayo Clinic staging system and 42% use the 2012 Mayo Clinic staging system for AL amyloidosis. Most HCPs treat all newly diagnosed AL patients with the same regimen (88%). HCPs primarily use D-CyBorD as their preferred FLT (88%). Less than 10% of HCPs use autologous stem cell transplants (ASCT) for FLT. One-quarter of clinicians routinely conduct bone marrow biopsies to confirm CR after FLT (25%). Nearly all HCPs participated in at least one interventional clinical trial (91%) for AL amyloidosis in the past 5 years, with average participation in 5 interventional trials (mean 4.81, SD 2.75). Most HCPs have participated in at least one observational clinical trial (66.7%) for AL amyloidosis with an average participation of 3 observational trials (mean 2.3, SD 1.8). Most HCPs were uncomfortable waiting for a patient's dFLC to rise to greater than 50 mg/L to meet eligibility for trials of relapsed/refractory AL amyloidosis patients. (60%).

Conclusions: These preliminary findings provide insight into HCPs real-world FLT preferences for AL amyloidosis patients. More than 90% of HCPs in our study prefer to use D-CyBorD as FLT, with less than 10% preferring ASCT as FLT. This is a significant shift from the 2017 study, which found that more than 70% of HCPs preferred ASCT as FLT, however this was conducted prior to FDA approval of daratumumab (2021). Like the 2017 study, most HCPs remain uncomfortable waiting for dFLC to rise to 50 mg/L to meet clinical trial eligibility for relapsed/refractory patients. The findings from our subsequent full analysis will provide additional insights into the real-world management of more advanced AL patients and may help inform future research.

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2025
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