Treatment-Related Symptoms and Impact on Health-Related Quality of Life in AL Amyloidosis
Authors: Bayliss Martha , White Michelle K. , McCausland Kristen , Oliver Colin , Guthrie Spencer D. 
Published: October 2019

Abstract
Introduction:Light-chain (AL) amyloidosis is a rare disease characterized by misfolded amyloid protein deposits in tissues and vital organs. Although no medications to treat AL amyloidosis have yet been approved by the United States Food and Drug Administration or the European Medicines Agency, chemotherapy, stem cell transplantation (SCT), and immunomodulatory drugs are used off-label. These treatments can be associated with treatment-related symptoms (TRSs). The objective of this study is to describe the history of TRSs and their impact on treatment regimens and HRQoL among a diverse sample of patients with AL amyloidosis.
Methods: We report data from a non-interventional cohort of community-based patients with self-reported AL amyloidosis. Patients who completed a baseline and six-month follow-up online survey to assess TRSs and HRQoL were included in this analysis (n=226). TRSs were assessed among ever treated patients (n=216) and patients who were treated in the past year (recently treated, n=111). The following aspects of TRSs were captured: 1) prevalence of TRSs; 2) consequences of recent TRSs (discontinuation of a treatment; reduction of a treatment; or maintenance of treatment despite TRSs); 3) severity of specific TRSs (five point scale with a symptom checklist: none, mild, moderate, severe, very severe); and 4) ability to tolerate current AL amyloidosis treatment (based on a 4 point scale from "extremely poorly" to "very well"). A three-level categorical variable (i.e. better, same, worse) was derived to classify individuals by how they ranked their ability to tolerate their treatment at baseline as compared to their ranking at follow-up. A generic measure of HRQoL, the SF-36v2 Health Survey® (SF-36v2), was used to measure eight domains and two component summary measures of functional health and well-being. Higher SF-36v2 scores represented better functioning. Changes in patients' ability to tolerate current treatments were evaluated in relation to changes in SF-36v2 scores using ANCOVA methods and controlling for baseline SF-36v2 scores.
Results:Three-quarters (79%) of all treated patients reported ever having problems tolerating AL amyloidosis treatment, of which nearly half (47%) discontinued at least one treatment; half (51%,) reduced at least one treatment; and half (51%) reported tolerability problems which did not lead to changes in treatment. Patients reported, on average, 3 moderate-to-severe TRSs. The most commonly reported moderate-to-severe TRSs included: fatigue (65%), neuropathy (36%), diarrhea (34%), and nausea (33%).
Among recently treated patients, 53% endorsed a ranking of less than "very good" ability to tolerate current treatment. Ability to tolerate current treatments improved in the past six months for approximately 32% of recently treated patients and declined in 16% of recently treated patients. On average, patients who reported an improvement in their ability to tolerate current treatments also reported positive changes in HRQoL. Conversely, patients who reported a decline in their ability to tolerate their current treatments reported declines in HRQoL. These associations were not significant; however, the patterns for most scales were in the expected directions (Figure 1).
Conclusion : Overall, patients' reported ability to tolerate treatment was poor. Lifetime history of TRSs was high. Discontinuation of AL amyloidosis treatment was fairly common, though most patients were able to tolerate their current regimen. The high prevalence of treatment discontinuation and history of multiple AL amyloidosis treatments suggests that physicians and patients try a variety of treatments to balance tolerability and efficacy. Findings related to change in ability to tolerate treatment six months after the initial survey suggest a relationship with changes in HRQoL. In some cases, the changes in HRQoL approached established minimally important differences which can alert clinicians to actual changes in functioning. While this relationship should be further tested with larger samples and longer follow-up periods, these findings highlight the importance of assessing HRQoL during treatment for AL amyloidosis to better understand tolerability, and the need for more treatment options for AL amyloidosis, particularly those with favorable tolerability.

Disclosures
Bayliss: Prothena Biosciences Inc: Research Funding. White:Prothena Biosciences Inc: Research Funding. McCausland:Prothena Biosciences Inc: Research Funding. Oliver:Prothena Biosciences, Inc.: Employment, Equity Ownership. Guthrie:Prothena: Employment, Equity Ownership, Other: Leadership.