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3238 Patient-Reported Quality of Life Outcomes with Venetoclax-Based First-Line Combinations in CLL: An Analysis from the Phase 3 GAIA/CLL13 Trial

Program: Oral and Poster Abstracts
Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, Lymphoid Leukemias, CLL, Clinical Research, Patient-reported outcomes, Diseases, Lymphoid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Moritz Fürstenau, MD1*, Emelie Curovic Rotbain, MD, PhD2*, Laura Eurelings, MD, PhD3*, Sandra Robrecht, PhD4*, Julia Von Tresckow, MD5*, Adam Giza6*, Michael Gregor, MD7*, Patrick Thornton8*, Philipp Bernhard Staber, MD, PhD9, Tamar Tadmor, MD10*, Vesa Lindström11*, Gunnar Juliusson, MD, PhD12, Ann Janssens, MD13*, Christof Schneider, MD14*, Thomas Noesslinger, MD15, Martin Andres16*, Adrian Schmidt17*, Elisabeth Vandenberghe, MD18, Lev Shvidel, MD19*, Christian Bjørn Poulsen, MD, PhD20*, Henrik Frederiksen, MD, PhD21, Caspar Da Cunha-Bang, MD, PhD2*, Kourosh Lotfi22*, Rogier Mous, MD PhD23*, Martine E.D. Chamuleau, MD PhD24, Ka Lung Wu25, Margriet Oosterveld, MD26*, Jesus Duque-Afonso, MD27*, Christian Bogner28*, Thomas Wolff, MD29*, Johannes Schetelig, MD, MSc30, Ursula Vehling-Kaiser, MD31*, Christoph van Roye32*, Nadine Kutsch, MD6*, Anna Maria Fink, MD33*, Kirsten Fischer, MD33*, Emily Holmes34*, Matthias Ritgen35*, Eugen Tausch, MD14*, Stephan Stilgenbauer, MD14, Michael J. Hallek, MD36, Arnon P. Kater, MD, PhD37, Carsten Utoft Niemann, MD, PhD2*, Mark-David Levin38 and Barbara F. Eichhorst, MD39

1Department I of Internal Medicine, Faculty of Medicine and Cologne University Hospital, Koeln, Germany
2Department of Hematology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
3Albert Schweitzer Ziekenhuis, Dordrecht, Netherlands
4German CLL Study Group, University of Cologne, Cologne, Germany
5Clinic for Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
6Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf; German CLL Study Group, University of Cologne, Cologne, Germany
7Division of Hematology, Cantonal Hospital of Lucerne, Lucerne, Switzerland, Lucerne, Switzerland
8Department of Haematology, Beaumont Hospital, RCSI, Cancer Trials Ireland, Dublin, Dublin, IRL
9Department of Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Vienna, Austria
10Bnai Zion, Haifa, Israel
11Comprehensive Cancer Center, Department of Hematology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
12Department of Hematology, Lund University Cancer Center, Lund, Sweden
13University Hospitals Leuven, Leuven, Belgium
14Department of Internal Medicine III, Division of CLL, University Hospital Ulm, Ulm, Germany
15Hanusch Hospital, Vienna, AUT
16Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
17Stadtspital Zürich Triemli, Zürich, Switzerland
18St. James's Hospital, Dublin, IRL
19Kaplan Medical Center, Rehovot, Israel, ISR
20Department of Hematology, Zealand University Hospital, Roskilde, Denmark
21Department of Hematology, Odense University Hospital, Odense, DNK
22University Hospital/Linkoping University, Linkoping, SWE
23Department of Hematology, University Medical Center Utrecht, Amsterdam, Netherlands
24Department of Hematology, Amsterdam UMC location Vrije Universiteit Amsterdam, Amsterdam, Netherlands
25ZNA Stuivenberg, Antwerp, Belgium
26Canisius-Wilhelmina Hospital, Nijmegen, NLD
27Univ. of Freiburg, Freiburg, DEU
28Klinikum Landshut, Landshut, DEU
29Onkologie-Lerchenfeld, Hamburg, DEU
30Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Saxony, Germany
31Outpatient Clinic, Landshut, Germany
32Onkologie Koblenz, Koblenz, Germany
33Department I of Internal Medicine, Faculty of Medicine and Cologne University Hospital, Cologne, Germany
34German CLL Study Group, University of Cologne, Cologne, Cologne, Germany
35Department of Internal Medicine II (Hematology/Oncology), University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany
36University of Cologne, Cologne, DEU
37Amsterdam University Medical Center, Amsterdam, on behalf of HOVON, Netherlands
38Albert Schweitzer Hospital, Dordrecht, Netherlands
39University Hospital Cologne, Cologne, Germany

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 treatment initiation in the RV arm (-5.4; -5.3; -5.5; -5.8; -7.3) and GV arm (-5.0; -4.3; -5.6; -5.5; -7.8), while with GIV (-0.2; +1.1; 0.0; -1.5; -5.1) and CIT (-1.3; -1.7; -3.8; -4.0; -3.7) similar mean changes from BL were reached later.

Similar temporal dynamics, i.e. later improvements in the CIT and GIV arms compared to RV and GV were also reported for physical functioning, role functioning, social functioning (all QLQ-C30) and physical condition (QLQ-CLL16).

Clinically meaningful improvements (≥MID of 8.9) in fatigue were reported in most patients across treatment arms with a median TUI of 7.5 months (CIT), 5.4 (RV), 5.7 (GV) and 5.8 (GIV). TUD in nausea/vomiting was worse with GIV compared to CIT (HR 1.46 [95%CI 1.08-1.98]) and to RV (HR 1.76 [1.31-2.37], while the comparison of GIV versus GV showed a HR of 1.34 [0.999-1.78]). In the GIV arm, patients also reported higher scores in diarrhea with mean changes from BL above the MID (10.4) at MO3 (+12.9), MO6 (+14.3) and MO9 (+12.9) and higher scores in bruising with a mean change from BL above the MID (10.7) at MO6 (+13.5), while the mean changes from BL did not reach the MID in the other arms at any time. The risk of a clinically meaningful deterioration of diarrhea was higher with GIV compared to CIT (TUD, HR 2.37 [1.74-3.23]), RV (HR 1.58 [1.21-2.07]) and GV (HR 1.53 [1.16-2.02]).

Conclusions

For patients treated with GV or RV, rapid improvements in QoL measures and key functioning scales were observed shortly after treatment initiation. Similar improvements were consistently reported later, after the end of treatment in patients receiving GIV, while later and smaller improvements were seen for patients receiving CIT. This difference in the timing of QoL improvements between the triple combination and the RV/GV doublets appeared to be driven by a higher symptom burden during treatment with GIV. This should be considered when comparing efficacy outcomes of different venetoclax combinations in CLL.

Disclosures: Fürstenau: Abbvie: Speakers Bureau. Rotbain: Abbvie: Consultancy; AstraZeneca: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees. Eurelings: Abbvie: Research Funding. Robrecht: AstraZeneca: Honoraria. Gregor: Johnson&Johnson: Honoraria; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria; Servier: Honoraria; GlaxoSmithKline: Honoraria; Roche: Honoraria; Amgen: Honoraria; AbbVie: Honoraria, Research Funding; AstraZeneca: Honoraria; BeiGene: Honoraria; Pfizer: Honoraria; Elli Lilly: Honoraria. Tadmor: Janssen, roche, abbvie, astra, takeda, novartis, beigene, medison: Consultancy, Research Funding. Schneider: Abbvie: Honoraria; AstraZeneca: Honoraria; Janssen-Cilag: Honoraria. Noesslinger: Roche: Honoraria; Abbvie: Honoraria; Janssen: Honoraria; AstraZeneca: Honoraria; Beigene: Honoraria; Lilly: Honoraria. Andres: Janssen: Honoraria, Other: travel support; Abbvie: Honoraria, Other: travel support; AstraZeneca: Honoraria, Other: travel support; BMS: Other: travel support; Novartis: Other: travel support; Roche: Other: travel support. Schmidt: Sobi: Consultancy, Other: travel support; Roche: Consultancy, Other: travel support; Sanofi: Consultancy; Takeda: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Beigene: Consultancy; Novartis: Consultancy; Incyte: Consultancy; Bayer: Other: travel support; Celgene: Other. Chamuleau: BMS/Celgene: Research Funding; GenMab: Research Funding; Gilead: Research Funding; AbbVie: Consultancy; Novartis: Consultancy; Incyte: Consultancy. Duque-Afonso: Roche: Honoraria; Amgen: Honoraria; AstraZeneca: Honoraria; Beigene: Honoraria, Other: travel support; Abbvie: Honoraria; Lilly: Honoraria; Janssen: Honoraria; Riemser: Honoraria; Ipsen: Honoraria; Sobi: Honoraria, Other: travel support; Alexion: Other: travel support; Gilead: Other: travel support. Wolff: Novartis, Celgene, Roche, Bayer, Teva and Abbvie: Consultancy. Schetelig: Eurocept: Honoraria; MSD: Consultancy; Janssen: Consultancy, Honoraria; Novartis: Honoraria; Astellas: Honoraria; Medac: Honoraria; AstraZeneca: Consultancy, Honoraria. Kutsch: BMS: Honoraria; Kite/Gilead: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Lilly: Honoraria, Other: Travel grants; BeiGene: Other: Travel grants; Abbvie: Honoraria, Other: Travel grants; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding. Fink: AstraZeneca: Honoraria, Research Funding. Fischer: AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Tausch: Abbvie: Consultancy, Other, Research Funding; Roche: Consultancy, Research Funding; BeiGene: Consultancy, Other; AstraZeneca: Consultancy; Janssen: Consultancy, Other. Stilgenbauer: Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Hoffmann-La Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Galapagos: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; BeiGene: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Lilly: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; Sunesis: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding, Speakers Bureau. Kater: AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Patents planned, issued or pending; Steering Committee, Research Funding; LAVA: Membership on an entity's Board of Directors or advisory committees, Other: Patents planned, issued or pending; Steering Committee; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Steering Committee, Research Funding. Niemann: AbbVie, Janssen, AstraZeneca, Novo Nordisk Foundation, Octapharma: Consultancy, Research Funding; Novo Nordisk: Research Funding; CSL Behring, Genmab, Takeda, Beigene, MSD, Lilly: Consultancy. Levin: Janssen, AbbVie: Other: Travel. Eichhorst: Miltenyi: Consultancy; MSD: Consultancy, Speakers Bureau; Hoffmann-La Roche: Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Kite: Consultancy, Speakers Bureau; BeiGene: Consultancy, Research Funding, Speakers Bureau; Roche: Research Funding, Speakers Bureau; AbbVie: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Lilly: Consultancy.

OffLabel Disclosure: The combination of venetoclax-ibrutinib-obinutuzumab is not approved for the treatment of CLL

*signifies non-member of ASH