Patient-Reported Quality of Life Outcomes with Venetoclax-Based First-Line Combinations in CLL: An Analysis from the Phase 3 GAIA/CLL13 Trial

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.3238-3238
• Main Authors: Fürstenau, Moritz, Rotbain, Emelie Curovic, Eurelings, Laura, Robrecht, Sandra, Von Tresckow, Julia, Giza, Adam, Gregor, Michael, Thornton, Patrick, Staber, Philipp Bernhard, Tadmor, Tamar, Lindström, Vesa, Juliusson, Gunnar, Janssens, Ann, Schneider, Christof, Noesslinger, Thomas, Andres, Martin, Schmidt, Adrian, Vandenberghe, Elisabeth, Shvidel, Lev, Poulsen, Christian Bjørn, Frederiksen, Henrik, Da Cunha-Bang, Caspar, Lotfi, Kourosh, Mous, Rogier, Chamuleau, Martine E.D., Wu, Ka Lung, Oosterveld, Margriet, Duque-Afonso, Jesus, Bogner, Christian, Wolff, Thomas, Schetelig, Johannes, Vehling-Kaiser, Ursula, van Roye, Christoph, Kutsch, Nadine, Fink, Anna Maria, Fischer, Kirsten, Holmes, Emily, Ritgen, Matthias, Tausch, Eugen, Stilgenbauer, Stephan, Hallek, Michael J., Kater, Arnon P., Niemann, Carsten Utoft, Levin, Mark-David, Eichhorst, Barbara F.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-198917

Background The phase 3 GAIA/CLL13 trial recently demonstrated superior progression-free survival for time-limited venetoclax-obinutuzumab (GV) and venetoclax-obinutuzumab-ibrutinib (GIV) compared to both, chemoimmunotherapy (CIT) and venetoclax-rituximab (RV) in the first-line treatment of CLL. Currently, no direct comparisons of health-related quality of life (QoL) measures of different venetoclax regimens are available. Here, we report a preplanned analysis of patient-reported QoL outcomes (PRO) from the GAIA/CLL13 trial. Methods PRO questionnaires were completed at baseline (BL), month 3 (MO3), MO6, MO9, MO12, MO15, MO18, MO21, MO24 and then annually until MO60. Changes in functioning scales, global health status (GHS)/QoL and symptoms were assessed using the EORTC QLQ-C30 and QLQ-CLL16 questionnaires. For functioning scales and GHS/QoL, higher scores indicate a better level of functioning/improvement of QoL, on symptom scales higher scores show a higher level of symptoms. The minimal important difference (MID) was defined as the minimal change from BL indicating a clinically meaningful improvement and was calculated using a distribution-based approach as previously described (e.g. van der Straten et al., Blood 2023). For patients who completed a questionnaire at baseline and at least at one further time point post-baseline, time until deterioration (TUD) and improvement (TUI) were calculated from start of treatment until deterioration or improvement of at least MID. Results In total, 863 of 926 patients (93.2%) returned at least one questionnaire. Completion rates were 76.0% at BL, 72.7% at MO3, 69.4% at MO6, 61.2% at MO9, 75.4% at MO12 and 49.2% at MO15. BL characteristics were balanced between patients evaluable and non-evaluable for QoL. Mean BL values for GHS were 68.4 (CIT), 67.9 (RV), 67.8 (GV) and 69.5 (GIV). In the RV and GV arm, GHS improved after initiation of treatment (mean change from BL, RV: +5.2 [MO3]; +6.1 [MO6]; +8.8 [MO9]; +9.4 [MO12]; +8.4 [MO15]; GV: +5.5; +5.1; +9.0; +9.3; +10.1) and mean changes from BL above the MID (5.9) were maintained throughout the study. In the GIV arm, no mean increase above the MID was observed during the first 12 months of treatment but at MO15 when most patients had finished treatment (+2.4; +0.2; +2.5; +4.4; +10.2). In the CIT arm (+1.3; -0.6; +4.9; +5.0; +5.4), the first mean improvement above MID was reported at MO24 (+6.1). The symptom burden (QLQ-CLL16 questionnaire, MID 7.3) improved promptly after