Interim analysis of a non-interventional prospective descriptive study to assess the impact on Patient´s well-being of fixed-time duration (FTD) and continuous oral regimens for newly diagnosed and relapsed/refractory (R/R) chronic lymphocytic leukem

Abstract Chronic lymphocytic leukemia (CLL) remains in most cases an incurable disease; and treatments often aim to improve quality of life and prolong survival. The PROVIDENCE study is an ongoing observational, prospective, multicenter Spanish study evaluating HRQoL during treatment using different questionnaires. This study primarily aims to assess the impact on patient's HRQoL of fixed time duration (FTD) Venetoclax-based regimen or continuous (C) oral BTKi regimens for the treatment of CLL.This interim analysis summarizes the results from validated PROMs including HRQoL scales EORTC QLQ-C30 and CLL17 at 3 months before (-3m) the expected End Of Treatment (EOT), at the expected EOT (0), and 3 months after the EOT (+3m) for patients receiving FTD and at the correspondent timepoints for patients on C regimens. A descriptive statistical analysis was performed. Means at each timepoint include all available data, while mean change scores (∆) were calculated using paired data only. For the intra group comparative analysis non-parametric Wilcoxon's test was used. The interim analysis from the results obtained from October 2023 through May 2025, included 77 patients from two cohorts: 46 patients under FTD (median age 67 years (58-74), 67.4% male) and 31 patients under C regimens (median age 68 years (60-79), 58.1% male). Incidence of uIGHV, del(17p) and/or TP53m and Complex Karyotype (≥5 aberrations) in assessed patients is 64% (N=27), 2% (N=1) and 13% (N=3) for the FTD and 58% (N=18), 46% (N=6) and 15% (N=2) for the C, respectively. At +3m, Complete Response was achieved in 90% (N=18) of FTD and in 33% (N=6) of C while Partial Response was achieved in 10% (N=2) for FTD and 67% (N=12) for C. Mean GHS/QoL (QLQ-30) scores at -3m, 0, and +3m were 71.9, 71.5 and 79.7 (∆mean +3.6 at -3m vs +3m, p>0.05) for FTD and 71.1, 65.1 and 63.2 (∆mean -6.7 at -3m vs 0, p≤0.05; -9.3 at -3m vs +3m, p≤0.05) for C. Overall significant improvements for FTD were observed for functioning scale ∆mean: Physical: +5.8 at -3m vs +3m, p≤0.05 and +5.5 at 0 vs +3m, p≤0.05; Role: +6.5 at 0 vs +3m, p≤0.05; Emotional: +3.6 at -3m vs +3m, p>0.05; Cognitive: +2.9 at 0 vs +3m, p>0.05; and Social: +3.6 at 0 vs +3m, p>0.05. Symptom scales ∆mean for FTD were: Fatigue: -3.4 at -3m vs +3m, p>0.05; Nausea and Vomiting: -5.1 at 0 vs +3m, p>0.05; Pain: -8.0 at 0 vs +3m, p≤0.05; Dyspnea: -5.8 at -3m vs +3m, p>0.05; Insomnia: -2.9 at 0 vs +3m, p>0.05; Appetite loss: -5.8 at 0 vs +3m, p>0.05; Constipation: -1.4 at 0 vs +3m, p>0.05; Diarrhea: -8.7 at -3 vs +3m, p>0.05; No significant functioning scale ∆mean were observed for C: Physical: +2.4 at -3m vs +3m, p>0.05; Role: -6.9 at -3m vs +3m, p>0.05; Emotional +5.4 at -3m vs +3m, p>0.05; Cognitive: -2.9 at 0 vs +3m, p>0.05; and Social: -1.0 at 0 vs +3m, p>0.05. Symptom scale ∆mean for C were: Fatigue: +2.0 at -3m vs +3m, p>0.05; Nausea and Vomiting: +2.9 at 0 vs +3m, p>0.05; Pain: 0.0 at 0 vs +3m, p>0.05; Dyspnea: +3.9 at -3m vs +3m, p>0.05; Insomnia: +3.9 at 0 vs +3m, p>0.05; Appetite loss: +3.9 at 0 vs +3m, p>0.05; Constipation: +11.8 at 0 vs +3m, p≤0.05; Diarrhea: -3.9 at -3m vs +3m, p>0.05. Financial difficulties ∆mean for FTD were: -4.3 at -3m vs +3m, p>0.05 and +2.0 at -3 vs +3m, p>0.05 for C. For QLQ-CLL17, physical condition/fatigue, symptom burden and worries/fears about health and functioning mean values at -3m, 0, +3m were 22, 21, 11 (∆mean -6.9 at -3m vs +3m, p≤0.05; -5.8 at 0 vs +3m, p≤0.05); 22, 24, 11 (∆mean -5.6 at 0 vs +3m, p≤0.05) and 25, 28,18 (∆mean -4.2 at 0 vs +3m, p>0.05) for FTD and 22, 23, 27 (∆mean +5.4 at -3m vs +3m, p>0.05); 27, 26, 30 (∆mean +6.5 at -3m vs +3m, p≤0.05) and 22, 25, 29 (∆mean +1.6 at 0 vs +3m, p>0.05) for C, respectively. In conclusion, patients on FTD Ven-based regimens demonstrated a general trend of improvement in GHS/QoL over time, with significant improvements observed for functioning and symptoms scales in physical, role functioning, pain, symptom burden and physical condition/fatigue. For the C, results were more variable with a significant decrease in GHS/QoL and a significant increase in symptom burden, including constipation. These interim results potentially demonstrate the benefit of FTD Venetoclax-based regimens in enhancing HRQoL in the real-world setting. The final study results will provide valuable input to confirm the significance of this data.