A Medical Chart Review of Healthcare Costs in Patients with Systemic Amyloid Light Chain Amyloidosis By Mayo 2012 Stage in the United States

Introduction: Systemic amyloid light chain (AL) amyloidosis is a rare disease with severe sequelae, including cardiac and renal dysfunction and failure. Various biomarker-based staging systems have been established to inform prognosis and treatment. However, a single International Classification of Diseases, Tenth Revision (ICD-10) diagnosis code collectively applies to all stages of the disease, and while several studies have reported disease costs using healthcare claims data, stage-specific costs are not well understood. The current study aimed to estimate the healthcare utilization and costs of prevalent patients with AL amyloidosis by Mayo 2012 stage (I, II, III, IV).

Methods: A multi-center medical chart review of patients with AL amyloidosis was conducted across six hematology clinics in the United States. Enrolled patients were ≥18 years old with a diagnosis of AL amyloidosis, documentation of Mayo 2012 stage at diagnosis, ≥1 office visit during the 6 months prior to the site's IRB approval date, and ≥1 year of available medical records. We collected 1 year of healthcare utilization data for each patient, in addition to clinical characteristics at diagnosis, which was prior to the 1-year observation period for most patients. Observation periods ranged from 11/2020 to 6/2023. Demographics, AL amyloidosis clinical history (e.g., organ involvement, lines of therapy, treatment response), laboratory values, and AL amyloidosis-related healthcare utilization (e.g., office visits, laboratory tests, procedures, medications, emergency department visits, inpatient stays) were collected. Patients were stratified by Mayo 2012 stage at diagnosis. Patients' 1-year healthcare costs were calculated by combining abstracted utilization data with the Centers for Medicare and Medicaid Services 2023 Physician Fee Schedule for procedures, Medi-Span® Price Rx® Pro for pharmacy and drug administration costs, and published literature for costs unavailable in these sources. Costs were adjusted to 2023 USD using the Consumer Price Index inflation calculator from the US Bureau of Labor Statistics.

Results: The study included 61 patients: 15 stage I, 16 stage II, 17 stage III, and 13 stage IV. Overall, patients had a mean age at diagnosis of 62.4 years (standard deviation ([SD] 10.1), 39.3% were female (n=24), and 67.2% (n=41) of patients were non-Hispanic White, 14.8 % (n=9) Non-Hispanic Black, 6.6% (n=4) Asian, 1.6% (n=1) Hispanic, and 9.8% (n=6) other race/ethnicity. Most patients had Medicare (45.9%, n=28) or private health insurance (34.4%, n=21). The average duration of disease (i.e., time from diagnosis to date of last office visit prior to their site's IRB approval date) was 4.5 years (SD 3.5). All patients had involvement of ≥1 organ system and 45.9% (n=28) had involvement of ≥2 organ systems at diagnosis. More than half of patients had renal (55.7%, n=34) or cardiac (52.5%, n=32) involvement. Nearly all patients completed first-line therapy at any point prior to their last office visit (93.4%, n=57); a minority of patients (9.8%, n=6) initiated first-line therapy, and 3 patients (4.9%) had a hematopoietic stem cell transplantation, one each in stages I, II, and III, during the study period. The median estimated AL amyloidosis-related healthcare costs (USD) during the 1-year study period were $95,253 (interquartile range [IQR] $2,869-497,504) for stage I, $190,796 ($5,249-499,470) for stage II, $414,677 ($28,365-533,081) for stage III, and $523,504 ($191,830-526,596) for stage IV.

Discussion: This is the first study of AL amyloidosis that reports costs of care stratified by Mayo 2012 stage. In a prevalent population with AL amyloidosis, we found that overall, patients with AL amyloidosis have significant ongoing costs of care after completion of initial therapy at each Mayo 2012 stage, with stage IV patients having the highest AL amyloidosis-related costs. The percent of patients with cardiac or renal organ involvement is possibly higher than represented in this study; given the rapid progression and high early mortality rate seen with stage III and IV disease, some of these patients may not have fulfilled the 1-year observation period requirement and thus were excluded from the study. These data describe the significant and continued burden faced by patients with AL amyloidosis and the health care system for the years beyond initial diagnosis and completion of front-line treatment.

Gertz:Alnylym: Honoraria; Ionis/Akcea: Honoraria; Prothena: Other: personal fees; Dava Oncology: Honoraria; Johnson & Johnson: Other: personal fees; Janssen: Other: personal fees; Medscape: Honoraria; Abbvie: Other: personal fees for Data Safety Monitoring board ; Sanofi: Other: personal fees; Alexion: Honoraria; Astra Zeneca: Honoraria. Landau:Abbvie, Immix Biopharma, Legend Biotech, Alexion, Prothena: Consultancy; Janssen, Alexion, Protego, Prothena: Research Funding. Sanchorawala:Pfizer, Janssen, Attralus, GateBio, Abbvie, BridgeBio: Consultancy; Proclara, Caelum, Abbvie, Janssen, Regeneron, Protego, Pharmatrace, Telix, Prothena, AstraZeneca, Nexcella: Membership on an entity's Board of Directors or advisory committees; Celgene, Millennium-Takeda, Janssen, Prothena, Sorrento, Karyopharm, Oncopeptide, Caelum, Alexion: Research Funding. Bhutani:Takeda: Research Funding; BMS: Research Funding; Janssen: Research Funding; Caribou Biosciences: Research Funding; Amgen: Research Funding; Abvvie: Research Funding. Zonder:Regeneron: Consultancy; BMS (employment of spouse): Current Employment; BMS, Janssen, RLL: Research Funding. Rosenzweig:Pfizer: Ended employment in the past 24 months, Research Funding; Janssen: Ended employment in the past 24 months, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ROMTech: Current equity holder in private company; BMS: Ended employment in the past 24 months, Speakers Bureau. Campos:PHAR (Partnership for Health Analytic Research): Current Employment, Other: I am an employee of PHAR, which was paid by Prothena Biosciences, Inc. to conduct the research described in the abstract.; Akcea, Amgen, Astellas, Biomarin Pharmaceuticals, Bristol-Myers Squibb, Celgene, Crinetics, Delfi Diagnostics, Dompé, Eisai, Exact Sciences, Genentech, Gilead, GRAIL, Greenwich Biosciences, Ionis, Janssen, Nobelpharma, Novartis, Pfizer, Prothena, Recordat: Other: PHAR also discloses financial relationships with these entities outside of the submitted work. Yermilov:PHAR (Partnership for Health Analytic Research): Current Employment, Other: I am an employee of PHAR, which was paid by Prothena Biosciences, Inc. to conduct the research described in the abstract. ; Akcea, Amgen, Astellas, Biomarin Pharmaceuticals, Bristol-Myers Squibb, Celgene, Crinetics, Delfi Diagnostics, Dompé, Eisai, Exact Sciences, Genentech, Gilead, GRAIL, Greenwich Biosciences, Ionis, Janssen, Nobelpharma, Novartis, Pfizer, Prothena, Recordat: Other: PHAR also discloses financial relationships with these entities outside of the submitted work; CAREMINDr: Current Employment, Current holder of stock options in a privately-held company. Chang:PHAR (Partnership for Health Analytic Research): Current Employment, Other: I am an employee of PHAR, which was paid by Prothena Biosciences, Inc. to conduct the research described in the abstract.; Akcea, Amgen, Astellas, Biomarin Pharmaceuticals, Bristol-Myers Squibb, Celgene, Crinetics, Delfi Diagnostics, Dompé, Eisai, Exact Sciences, Genentech, Gilead, GRAIL, Greenwich Biosciences, Ionis, Janssen, Nobelpharma, Novartis, Pfizer, Prothena, Recordat: Other: PHAR also discloses financial relationships with these entities outside of the submitted work. Broder:PHAR (Partnership for Health Analytic Research): Other: I am an employee of PHAR, which was paid by Prothena Biosciences, Inc. to conduct the research described in the abstract.; Akcea, Amgen, Astellas, Biomarin Pharmaceuticals, Bristol-Myers Squibb, Celgene, Crinetics, Delfi Diagnostics, Dompé, Eisai, Exact Sciences, Genentech, Gilead, GRAIL, Greenwich Biosciences, Ionis, Janssen, Nobelpharma, Novartis, Pfizer, Prothena, Recordat: Other: PHAR also discloses financial relationships with these entities outside of the submitted work. Bajaj:Prothena Biosciences, Inc: Current Employment, Current equity holder in publicly-traded company; Roche/Genentech: Current equity holder in publicly-traded company, Other: Former employee.