Patient Experience with Venetoclax+Rituximab and BTK Inhibitors in Relapsed or Refractory Chronic Lymphocytic Leukaemia (CLL): A Qualitative Interview Study in the UK (ELECTRIC)
Authors: el-Sharkawi Dima , Rahman Deborah , Lowry Lisa , Kelly Jo , Kew Hanna , Shah Nimish , Martins Daniel , Kent Toby , Powell Louise , Manzoor Beenish , Martinez-Calle Nicolas 
Published: December 2024

Background
Venetoclax+Rituximab (Ven+R) and Bruton's tyrosine kinase inhibitors (BTKis) have improved outcomes for relapsed or refractory (R/R) CLL compared with chemoimmunotherapy and offer patients a choice of fixed-duration treatment (FDT) or treatment to progression (TTP) modalities. Clinical trials do not fully capture the patient experience and with multiple treatment options available, deeper insights are needed to understand patients' needs and support treatment decision making. This study explores the patient experience at key timepoints during their second line (2L) treatment with Ven+R and BTKis.
Methods
This cross-sectional, qualitative study was conducted between November 2022 and April 2024 using semi-structured concept-elicitation interviews to evaluate decision-making processes, symptoms experienced by patients and their impact on daily lives. Open-ended questions and prompts from a predetermined list of symptoms and impacts were used. Severity of symptoms, level of disruption and treatment satisfaction were assessed using an 11-point Likert scale. Qualitative data analysis employed an iterative thematic approach, while descriptive statistics summarised quantitative and categorical variables.
Results
100 patients (n=58 Ven+R; n=42 BTKi) were interviewed across 16 UK sites. Concept saturation performed on symptoms was achieved across all sub cohorts.
Symptom Burden Before Treatment: Most common symptoms were fatigue (84%) and swollen lymph nodes (66%). Other symptoms included bruising (49%), night sweats (49%), muscle/joint aches (45%), shortness of breath (45%), weight loss (45%) and infections (44%), all were perceived as troublesome. Patients reported their CLL symptoms impacted daily activities, physical, emotional, and social functioning. Whilst depression caused the highest level of disruption (mean 7.1 [SD 2.4]), social functioning was also disrupted evidenced by decreased participation in groups (7.0 [2.4]) and ability to fulfil social/family roles (6.8 [2.5]).
Symptom Reduction (Frequency and Severity): Following treatment initiation, most patients experienced general symptom improvement (&gt;80% for Ven+R and BTKi). Prevalence of symptoms decreased following treatment initiation with both Ven+R and BTKi for most of the symptoms reported frequently. Differences between treatments were observed in bruising, which decreased with Ven+R from 47% to 38% and increased from 52% to 64% with BTKi. Similarly, muscle/joint aches decreased from 45% to 24% with Ven+R and slightly increased from 45% to 48% with BTKi. Fatigue/tiredness was less common following BTKi (from 79% to 55%) than Ven+R treatment (from 88% to 78%). Treatment emergent symptoms with Ven+R included diarrhoea (from 21% to 28%) and nausea/vomiting (from 22% to 29%).
Treatment Satisfaction: Treatment satisfaction was high for both Ven+R and BTKi with a mean satisfaction score of 9.39 [1.03] and 9.05 [2.01], respectively with the highest level of satisfaction reported after FDT (9.53 [0.96]).
Shared Decision Making (SDM): 50% of patients reported their healthcare provider did not discuss both continuous treatment and FDT options. If given the choice, 17% of respondents treated with BTKi would have preferred FDT, while only 7% of respondents treated with Ven+R would have chosen continuous treatment.
Conclusion
To our knowledge, this study represents the largest assessment of the patient experience in R/R CLL. These findings highlight the substantial burden of symptoms experienced by patients prior to initiating 2L treatment, some of which are not listed as constitutional symptoms in the iwCLL criteria, but greatly impact quality of life indicating the true extent of symptom burden in the months pre-treatment may be underestimated in clinical practice.
Both treatment options improved most troublesome symptoms with improvement sustained beyond completion of FDT in the Ven+R group. This is reflected in the consistently high treatment satisfaction for both treatments, with the highest level of satisfaction for Ven+R post-FDT, underscoring the enduring off-treatment benefits of Ven+R. Only half of the patients discussed treatment options with their healthcare provider despite variability of preferences for treatment approaches among patients, emphasizing the importance of SDM in treatment planning to ensure that individual patient needs are appropriately met.