Long-term quality of life of patients with acute promyelocytic leukemia treated with arsenic trioxide vs chemotherapy

Abstract

The main objective of this study was to compare the long-term health-related quality of life of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) vs ATRA plus standard chemotherapy. Patients previously enrolled in the randomized controlled trial APL0406 were considered eligible for this follow-up study. The following patient-reported outcome measures were used: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30), the EORTC Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20), and the Short Form Health Survey 36 (SF-36). The prevalence of late comorbidities and health problems was also assessed. The clinical significance of differences was evaluated based on predefined thresholds. A total of 161 of 232 potentially eligible patients were analyzed, of whom 83 were treated with ATRA-ATO and 78 were treated with ATRA chemotherapy. The median time since diagnosis of the study sample was 8 years. The 2 largest clinically meaningful differences in the EORTC QLQ-C30 were observed for role functioning (Δ = 8.4; 95% confidence interval [CI], 0.5 to 16.3) and dyspnea (Δ = -8.5; 95% CI, -16.4 to -0.7), favoring patients treated with ATRA-ATO. With regard to the SF-36 results, a clinically relevant better physical component score (Δ = 4.6; 95% CI, 1.3 to 7.8) was observed in patients treated with ATRA-ATO, but this was not the case for the mental component score. The 2 groups showed similar profiles in the scores of the EORTC QLQ-CIPN20 scales and in the prevalence of late comorbidities. Overall, our findings suggest that the greater and more sustained antileukemic efficacy of ATRA-ATO is also associated with better long-term patient-reported outcomes than ATRA chemotherapy. This study was registered at www.clinicaltrials.gov as #NCT03096496.

© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Figures

Graphical abstract

Figure 1.

Adjusted mean differences in HRQoL profile by the EORTC QLQ-C30 questionnaire between patients with APL previously treated with ATRA-ATO vs ATRA chemotherapy. The figure represents differences in mean scores and corresponding 95% CIs, adjusted for time since protocol completion, of functional and global QoL scales (A) and symptom scales (B) from the EORTC QLQ-C30 questionnaire between long-term APL survivors previously treated with ATRA plus arsenic trioxide or ATRA plus chemotherapy. For descriptive purposes, the mean difference scores and corresponding 95% CIs of the symptom scales were multiplied by −1. Positive differences in functional and symptom scales indicate better outcomes in the ATRA plus arsenic trioxide arm than in the ATRA plus chemotherapy arm. A red circle indicates a clinically relevant difference.

Figure 2.

Adjusted mean differences in physical and mental health-related domains by the SF-36 questionnaire between patients with APL previously treated with ATRA-ATO vs ATRA chemotherapy. The figure represents the differences in mean scores and corresponding 95% CIs, adjusted for time since protocol completion, of physical (A) and mental health-related scales (B) from the SF-36 questionnaire between long-term APL survivors previously treated with ATRA plus arsenic trioxide or ATRA plus chemotherapy. A positive difference in all scales indicates better outcomes in the ATRA plus arsenic trioxide arm than in the ATRA plus chemotherapy arm. A red circle indicates a clinically relevant difference.

Figure 3.

Adjusted mean differences in SF-36 physical and mental health component scores between patients with APL previously treated with ATRA-ATO vs ATRA chemotherapy. The figure represents the differences in mean scores and corresponding 95% CIs, adjusted for time since protocol completion, of physical (A) and mental component summary scales (B) from the SF-36 questionnaire between long-term APL survivors previously treated with ATRA plus arsenic trioxide or ATRA plus chemotherapy. A positive difference in all scales indicates better outcomes in the ATRA plus arsenic trioxide arm than in the ATRA plus chemotherapy arm. A red square indicates a clinically relevant difference.

Figure 4.

Adjusted mean differences in SF-36 scores between patients with APL previously treated with ATRA-ATO and the general population. Patients with APL and subjects from the general population had been previously matched by the propensity scores estimated on age and sex. *Clinically relevant difference.