Chronic Lymphocytic Leukemia (CLL) Patients Quality of Life (QoL): A Cross-Sectional Analysis of the Italian Experience in the Choice Study during the First Wave of the COVID-19 Pandemic
Authors: Tedeschi Alessandra , Innocenti Idanna , Albano Francesco , Gozzetti Alessandro , Levato Luciano , Porrazzo Marika , Reda Gianluigi , Albi Elisa , Chiarenza Annalisa , Gualberti Giuliana , Malgieri Simona , Finsinger Paola , Trentin Livio 
Published: November 2021

Abstract
Introduction
Although plenty of data exists on efficacy and safety of CLL drugs, their impact on patients' Health-Related Quality of Life (HRQoL) is largely unknown (1-2). Documentation of drug safety via traditional use of adverse events (AE) in hematology is limited if not complemented with Patient-Reported Outcomes (PRO) measures (3-4). Incorporation of HRQoL PROs is now essential to better evaluate risk-benefit of new therapeutic approaches and it is also highly valued by regulatory stakeholders (5). Most PRO data currently available for CLL patients (pts) came from randomized controlled trial settings (6-7), hence limiting generalizability of findings to CLL real-life patients. CHOICE study was designed to investigate CLL patients' QoL and preference towards different treatment profiles through a Discrete Choice Experiment (DCE) methodology in Italy. Due to the timelines of the study, which started in February 2020, the related data offer an insight into patients' perception and worries during the first wave of the COVID-19 pandemic.
Methods
This cross sectional, multi-center, observational study included CLL patients, treatment naïve during the watch & wait period (W&W) or already TREATED (around 50% each, controlled at site level), who signed the informed consent for study participation. Exclusion criteria were inability to take oral drugs, cognitive disorders that could impair the comprehension of the questionnaires and concomitant treatment for other malignancies.
Patients were asked to fill in the following HRQoL questionnaires: EQ-5D-5L, EORTC QLQ-C30 and QLQ CLL-16, as well as a DCE questionnaire, (described elsewhere). Each questionnaire was completed by the patient on a tablet - using an App specifically developed for the study.
Results
401 pts were enrolled in Italy in 16 hematology centers (Feb - July 2020); 199 W&W and 196 TREATED pts completed the questionnaires and were included in the evaluable population.
Main patients' characteristics are shown in Table 1.
73.7% of TREATED pts were ON-treatment (30.8% were in 1st-line, 69,2% in further lines) and 26.3% were OFF-treatment; the majority of pts (55,6%) were currently treated with a target therapy (Table1).
The EQ-5D-5L questionnaire showed no significant differences between groups. In both groups more than 80% of pts reported low values (1 or 2, indicating no or small impact) on all items. Median VAS was 75 for the TREATED group and 80 for the W&W group (0-100; higher scores indicate higher QoL).
QLQ C-30 / CLL-16 scores had very similar results between TREATED and W&W pts suggesting a limited impact of CLL on pts QoL. The median (IQR) QoL Scale was 83.3 (67- 83) for TREATED and 83.3 (67- 92) for W&W pts (0-100; all functional scales had high scores, that represent a better level of functioning; all symptoms' scales had low values, representing a less important symptomatology or problem, Figure 1). The main symptoms reported were fatigue, insomnia, pain, and dyspnea, while the main worry was for "future health" (Figure 1).
Distribution of data was statistically different between the 2 groups only for the Role functioning Scale (p=0.024) and the Social Functioning Scale (p=0.003) of QLQ-C30 and for the Infection Scale (p&lt;0.001) of QLQ CLL-16, always with slightly but significantly better results for the W&W group.
Conclusions
CHOICE study helps to understand the CLL patients' mindset and feeling in the light of the COVID-19 pandemic impact on health care for this category of pts, highlighting their preferences and worries in a large cohort of pts in Italy, allowing a comparison between TREATED and W&W pts. The main limitation of the study was its cross-sectional design, which does not allow us to evaluate any change in QoL neither with respect to the impact of the pandemic, nor to the effects of the treatment, if any.
CLL pts showed a good QoL, as confirmed by both EQ-5D-5L and EORTC QLQ C-30 / CLL-16 scores, with very similar results between TREATED and W&W pts (although slightly better results in the W&W vs TREATED group). The results of the present study are consistent with previous reports, and fatigue was the most reported symptom, while worry for future health was the most relevant score in CLL-16 questionnaire. Hospital accesses reduction that was detected during the pandemic might have influenced patients' response, as well as the extreme attention towards the danger of infections, and might have impacted patients' perception on future health.
Figure 1 Figure 1.

Disclosures
Tedeschi: Beigene: Honoraria, Speakers Bureau; AstraZeneca: Honoraria, Speakers Bureau; AbbVie: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau. Gozzetti: Janssen: Honoraria; AbbVie: Honoraria. Reda: Beigene: Consultancy; Astra Zeneca: Consultancy; Abbvie: Consultancy; Janssen: Consultancy. Gualberti: AbbVie: Current Employment. Malgieri: AbbVie: Current Employment. Finsinger: AbbVie: Current Employment.