Patient-Reported Outcomes in Systemic Light-Chain Amyloidosis
Authors: Chakraborty Rajshekhar , Rybicki Lisa , Samaras Christy J. , Faiman Beth M. , Valent Jason , Majhail Navneet S. 
Published: October 2019

Abstract
Background: Patients with systemic light-chain (AL) amyloidosis have a high symptom burden which can negatively impact their health-related quality of life (HRQoL). However, there is a lack of data on patient-reported outcomes (PROs) in this population in the current era of effective plasma cell directed therapies. The primary objectives of our study were to assess baseline HRQoL using FACT-G (Functional Assessment of Cancer Therapy-General) and PROMIS-GH (Patient Reported Outcomes Measurement Information System-Global Health), evaluate the degree of correlation between FACT-G and PROMIS-GH, and compare HRQoL by hematologic response to first-line therapy in systemic AL amyloidosis.
Method: This was an observational study using the Cleveland Clinic Knowledge Program database, which contains HRQoL data captured at outpatient visits. FACT-G was administered every 90 days since its implementation on September 2012. PROMIS-GH was implemented in October 2015, initially administered every 30 days and subsequently every 90 days since July 2017.
Results: A total of 81 patients with systemic AL amyloidosis diagnosed between September 2012 and December 2017 and ≥1 HRQoL measurement were included in our analysis. The median age at diagnosis was 64 years. Cardiac involvement at diagnosis was present in 49% of patients. The most common induction therapy was Bortezomib-Cyclophosphamide-Dexamethasone (86%). Autologous stem cell transplantation was performed in 38% of patients.
Data on HRQoL at baseline (≤2 months from diagnosis) using FACT-G was available for 43 patients. The mean FACT-G total score at baseline was 74 (standard deviation [S.D.] ±15). In comparison, the mean FACT-G total score for general US population is 80.1 (±18.1) and that of US cancer patients is 79.3 (±17.0) [Normative data from Pearman et al; Cancer. 2014]. Maximal HRQoL deficit was seen in the functional well-being (FWB) domain of FACT-G, with the mean score being >0.5 S.D. below that of the general population (Table 1). Data on HRQoL at baseline using PROMIS-GH was available for 18 patients. There was a significant deficit in global physical health (GPH) compared to the general population, with a mean T-score of 37.7 (±7.8) [Mean T-score in general US population being 50±10]. The mean T-score for global mental health (GMH) was 44.4 (±6.7).
A total of 72 patients had 128 outpatient visits where FACT-G and PROMIS-GH were captured concurrently (range, 1-4 visits per patient). Using Cohen's criterion, GPH domain of PROMIS-GH had a large and statistically significant correlation with FACT-G total (r=0.66), physical well being (PWB) (r=0.77) and FWB (r=0.66) scores. PROMIS GMH domain also had a strong and statistically significant correlation with FACT-G total (r=0.73), PWB (r=0.60), emotional well-being (EWB) (r=0.64) and FWB (r=0.73) scores. The scatterplots for correlation between PROMIS-GH domains and FACT-G total score is shown in Figure I.
At follow-up, a total of 50 patients had data on best hematologic response and HRQoL assessment. Patients achieving a complete response (CR) to first-line therapy had a significantly superior FACT-G score at all domains compared to those with less than CR or no response. Maximal benefit in complete responders was noted in the FWB domain of FACT-G (Mean score ≥2 S.D. higher than patients with less than CR or no response; P=0.002).
Conclusion: Patients with AL amyloidosis have a worse HRQoL at diagnosis compared to US cancer and general adult population. Deficit in HRQoL was most prominent in the FWB domain of FACT-G and GPH domain of PROMIS-GH. Most domains of FACT-G and PROMIS-GH had strong and significant correlation. Patients achieving a CR to first-line therapy had significantly superior HRQoL at all FACT-G domains. Clinical trials in AL amyloidosis should include patient-reported HRQoL as a key endpoint and focus on the domains of physical health and functioning to assess meaningful benefit of novel therapies. Psychometric validation of FACT-G and PROMIS-GH in AL amyloidosis would be helpful in generating robust PRO data in future studies.

Disclosures
Majhail: Anthem, Inc.: Consultancy; Incyte: Honoraria; Atara: Honoraria.