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1859 Impact of Ibrutinib on Quality of Life in Patients with Early-Stage, Asymptomatic Chronic Lymphocytic Leukemia: Results from the Phase III CLL12 Trial

Program: Oral and Poster Abstracts
Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research, Health outcomes research, Patient-reported outcomes
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Ellinor Goergen, MD1*, Sandra Robrecht, PhD1*, Adam Giza1*, Can Zhang, PhD1*, Pascal Nieper, MD1*, Florian Simon, MD1*, Paula Cramer, MD1*, Moritz Fürstenau, MD1*, Othman Al-Sawaf, MD1, Nadine Kutsch, MD1*, Anna Maria Fink, MD1*, Ursula Vehling-Kaiser, MD2*, Lothar Müller, MD3*, Michael J. Eckart, MD4*, Rudolf Schlag, MD5*, Werner Freier, MD6*, Tobias Gaska, MD7, Christina Balser, MD8*, Marcel Reiser, MD9*, Martina Beate Stauch, MD10*, Clemens-Martin Wendtner, MD11*, Eugen Tausch, MD12*, Christof Schneider, MD12*, Kirsten Fischer, MD1*, Stephan Stilgenbauer, MD12,13, Barbara F. Eichhorst, MD1, Michael Hallek, MD1* and Petra Langerbeins1*

1Faculty 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
2Outpatient Clinic, Landshut, Germany
3Study Centrum Unter Ems, Practice for Oncology and Hematology, Leer, Germany
4Onkologische Schwerpunktpraxis Erlangen, Erlangen, Germany
5Practice for Hematology and Oncology Wuerzburg, Wuerzburg, Germany
6Medicinum, Hildesheim, Germany
7Brüderkrankenhaus St. Josef, Paderborn, Germany
8Oncological Practise Marburg, Marburg, He, DEU
9Praxis für internistische Onkologie und Hämatologie (PIOH), Frechen, Germany
10Praxis (Private Practice) Dr, Stauch, Kronach, Germany
11Medical Clinic III, Ludwig-Maximilians University (LMU), Munich, Germany, Munich, Germany
12Department of Internal Medicine III, Division of CLL, University Hospital Ulm, Ulm, Germany
13Comprehensive Cancer Center Ulm, University of Ulm, Ulm, Germany

Background

The impact of treatment on quality of life (QoL), as compared to the effect of CLL alone, is not well studied. We analysed patient (pt)-reported QoL outcomes (PRO) of treatment-naïve, asymptomatic, early-stage pts treated with ibrutinib (n=182) or placebo (n=181) in the double-blind, randomized, phase III CLL12 trial (ClinicalTrials.gov/NCT02863718). The final analysis of the trial has shown (Langerbeins et al., Hemasphere 2023) that ibrutinib did not prolong the overall survival compared to placebo despite increasing event-free survival.

Methods

PRO questionnaires were regularly completed at baseline (BL), during treatment (TP) and follow-up phase (FUP) (i.e. 3-monthly in the first year of treatment, 6-monthly in the following years of treatment and yearly in the follow-up phase). 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, higher scores indicated a better level of functioning/improvement of QoL, on symptom scales higher scores showed 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 (van der Straten, Blood 2023). For pts who completed a questionnaire at BL and at least at one further time point post-BL, time to deterioration (TUD) and improvement (TUI) were calculated from start of treatment until deterioration or improvement by at least a MID.

Results

With a median observation time of 66.4 months (range, 0 - 93.4), 328 of 363 pts (90.4%) returned at least one questionnaire. Completion rates were 67.5% at BL, 74.0% at TP MO0-6, 75.4% at TP MO6-12, 72.3% at TP MO12-18 and 79.1% at TP MO18-24.

Mean BL values for GHS were 75.5 (ibrutinib, I) and 71.8 (placebo, PBO). The BL values for GHS did not differ significantly in either group, nor did they show any notable changes throughout treatment for the I and PBO group: 72.3 and 72.2 for MO0-6, 73.8 and 72.0 for MO6-12, 74.5 and 71.7 for MO12-18, 74.3 and 70.5 for MO18-24, 74.6 and 70.1 for MO24-30, 75.4 and 69.4 for MO30-36, 76.1 and 69.3 for MO36-48, 71.9 and 70.0 for MO48-60, 74.9 and 72.0 for MO60+. The mean values for physical functioning did not differ between I versus PBO treated pts. Similar results were found for fatigue/physical condition and symptom burden using QLQ-CLL16.

TUD did not significantly differ for GHS (HR 1.009, 95%-CI 0.738-1.378; P =0.957) in treated versus untreated pts. Using EORTC QLQ-C30, TUI did not differ significantly for fatigue (HR 1.095; 95%-CI 0.793-1.512; P=0.581). However, TUI of physical functioning was shorter in the I group (HR 1.427; 95%-CI 1.023-1.992; P=0.036) with a median of 9.6 versus 18.1 months.

When evaluating the impact of I-associated toxicity on QoL, the TUD for diarrhea (HR 1.143; 95%-CI 0.798-1.636; P=0.466) or skin problems (HR 1.284; 95%-CI 0.924-1.786; P=0.137) did not differ in both groups. In contrast, the TUD of bruising was shorter in the I group with 19.3 versus 51.6 months (HR 1.822; 95%-CI 1.288-2.577; P <0.001).

Conclusions

In conclusion, ibrutinib therapy failed to show a major impact on global health status and on various QoL parameters in early-stage, asymptomatic CLL patients. Exceptions were a faster improvement in physical functioning and a shorter time to deterioration of bruising for patients treated with ibrutinib compared to placebo.

Disclosures: Goergen: AstraZeneca: Honoraria; AbbVie: Honoraria. Robrecht: AstraZeneca: Honoraria. Simon: AstraZeneca: Research Funding, Speakers Bureau; Lilly: Other: Travel Support. Fürstenau: Abbvie: Speakers Bureau. Al-Sawaf: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Eli Lilly: Honoraria, Membership on an entity's Board of Directors or advisory committees; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Ascentage: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kutsch: BeiGene: Other: Travel grants; Astra Zeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding; Abbvie: Honoraria, Other: Travel grants; 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. Fink: AstraZeneca: Honoraria, Research Funding. Wendtner: Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding; BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding. Tausch: Abbvie: Consultancy, Other, Research Funding; AstraZeneca: Consultancy; BeiGene: Consultancy, Other; Roche: Consultancy, Research Funding; Janssen: Consultancy, Other. Schneider: Abbvie: Honoraria; AstraZeneca: Honoraria; Janssen-Cilag: Honoraria. Fischer: Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees. 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. Eichhorst: Miltenyi: Consultancy; Kite: Consultancy, Speakers Bureau; BeiGene: Consultancy, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; MSD: Consultancy, Speakers Bureau; Roche: Research Funding, Speakers Bureau; Lilly: Consultancy; AbbVie: Consultancy, Research Funding, Speakers Bureau; Hoffmann-La Roche: Research Funding, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau. Hallek: AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Langerbeins: AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants, Research Funding; BeiGene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Hoffmann-La Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel grants.

*signifies non-member of ASH