AL Amyloidosis and Patient Reported Quality of Life
Authors: Warsame Rahma , Kumar Shaji , Thompson Carrie A. , Gertz Morie A. , Lacy Martha Q. , Buadi Francis , Hayman Suzanne R. , Leung Nelson , Dingli David , Hwa Yi L. , Lust John A. , Kapoor Prashant , Lin Yi , Go Ronald S. , Zeldenrust Steven R. , Kyle Robert A. , Rajkumar S. Vincent , Dispenzieri Angela 
Published: October 2019

Background: Patients with light chain amyloidosis (AL) often have delayed diagnosis and present with significant symptomatology; this may result in decreased quality of life (QOL). With improving treatment options providing longer survival, it is increasingly important to assess QOL. However there is paucity of data in the literature addressing QOL in AL patients. We prospectively employ a "Hematology Patient Reported Symptom Screen" (HPRSS) which consists of three questions about fatigue, pain and overall QOL. The aim of this study is to understand if HPRSS parameters predict various clinical outcomes.

Methods: Eligibility for this retrospective study was as follows: 1) New diagnosis of AL between 2009-2014; 2) baseline HPRSS documented in the medical record; and 3) at least a year of follow-up, which included either death within or follow-up through 12 months after diagnosis. The HPRSS questions were rated on a 1-10 scale, with 10 being the worst for fatigue and pain, and 10 being the best for overall QOL. Scores were abstracted from visits at time of diagnosis, and at 12 months +/- 1 month post-diagnosis. We considered a 2-point difference in serial scores a "change" over time.

Results: For the 302 patients in this study, the baseline median scores [interquartile range] for fatigue, pain, and QOL were 6 [3,7], 2 [0,5] and 5 [3,8], respectively. Median overall survival (OS) was 39.1 months, with 102 deaths in the first year. There were significant differences in baseline HPRSS between those who lived longer than one year and the early death patients in the domains of fatigue (5 [IQR 3, 7] vs. 7 [IQR 5, 8], p<0.0001) and QOL (6 [IQR 4, 8] vs. 5 [IQR 3, 7], p=0.006), but not in pain (2 [IQR 0, 5] vs. 2 [IQR 0, 5]). There were significant baseline differences in the early death group for alkaline phosphatase, bilirubin, creatinine, and Mayo stage. Patients who received ASCT had the best baseline fatigue 4 [2.5,6] and QOL 7 [5,8] scores and were significantly different from those who did not receive ASCT [fatigue p<0.0001) and QOL (p<0.0001)] On univariate analysis fatigue and QOL were prognostic for OS. On multivariate analysis Mayo 2012 staging, autologous stem cell transplant and baseline fatigue remained independently prognostic.

When analyses were restricted to the 125 patients with HPRSS measurements at 12 months, we found that over time QOL scores improved significantly 6 [IQR 3.5, 8] to 7 [IQR 5, 8] (two sided Wilcoxon signed rank p=0.01), but fatigue (5 [IQR 2, 5] to 4.5 [IQR 3, 6]) and pain scores (2 [IQR 0 ,4] to 1.5 [IQR 0, 4]) did not. Patients with worse baseline parameters tended to have improvement in QOL by 12 months while those with the best baseline parameters tended to decline in QOL although not statistically significant. When we included the 102 patients who died within 12 months to the comparison, the early death patients had the worst baseline parameters and there were significant differences across all 4 groups for most characteristics (Table 1). There was no association between achieving hematologic or organ response with change in QOL.

Conclusion: Asking patients with AL to rate their fatigue and QOL using a 10-point scale has predictive value. Patient reported fatigue at diagnosis is an independent prognostic factor for survival. Survival at one year was associated with significant improvement in QOL.

Table 1. Baseline parameters between patients with early death and/or survive 12 months. Grouped by Patient Reported QOL at 12 months Relative to Baseline Dead by 12 months, n=102 Improved, n=44 Stable, n=55 Worsened, n=26 pa HPRSS scores [IQR] Baseline QOL Baseline fatigue Baseline pain 12 month QOL 12 month fatigue 12 month pain 5 [3,7] 7 [5,8] 2 [0,5] NA NA NA 4 [3-5] b,c,d6 [4-8] b,c2 [0-4] 7 [6-9] b,d4 [1.25-6] 1 [0-3] 7 [4-8] 4 [2-7] 2 [1-5] 7 [4-8] 5 [3-6] 2 [0-4] 8 [7-10] 2.5 [0-5.25] 2 [0-6.25] 5 [3-7] 5 [3-6] 2.5 [1-4] <0.0001 <0.0001 NS NS 0.001 NS dFLC, mg/dL 48 (2.89-726) 30 (1.1-494) 19 (36-455) 22 (0.2-2097) 0.008 Troponin, ng/mL 0.065 (<0.01-0.84) 0.02 (<0.01-1.6) 0.01 (<0.01-0.19) 0.01 (<0.01-0.14) <0.0001 NT-proBNP pg/mL 5222 (159-70,000) 1766 (26-16868) 1381 (24-19180) 496 (56-2973) <0.0001 Received Transplant (%) 4 (4) 13 (33) 36 (50) 13 (50) 0.0002 a Significant by Wilcoxon across all 4 categories; b Significant difference between Improved and Worsened; c Significant difference between Improved and Stable; d Significant difference between Worsened and Stable

Disclosures

Kumar: Millenium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Abbvie: Research Funding; Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Research Funding; Onyx: Consultancy, Research Funding. Thompson:Kite Pharma: Research Funding.