Health-related quality-of-life in treatment-naive CLL/SLL patients treated with zanubrutinib versus bendamustine plus rituximab

Abstract

Objective

Zanubrutinib is a highly selective, next-generation Bruton’s tyrosine kinase inhibitor. In the phase 3 SEQUOIA trial (NCT03336333), treatment with zanubrutinib resulted in significantly improved progression-free survival compared to bendamustine plus rituximab (BR) in adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) without del(17p). The current analysis compared the effects of zanubrutinib versus BR on patients’ health-related quality-of-life (HRQoL).

Methods

In the SEQUOIA trial, patient-reported outcomes (PROs) were assessed at baseline and every 12 weeks (3 cycles) using the EORTC QLQ-C30 and EQ-5D-5L. Descriptive analyses were performed on all the questionnaires’ scales and a mixed model for repeated measures was performed using the key QLQ-C30 endpoints of global health status/QoL (GHS/QoL), physical and role functioning, and symptoms of fatigue, pain, diarrhea, and nausea/vomiting at weeks 12 and 24.

Results

Compared with BR-treated patients, those in the zanubrutinib arm experienced greater improvements in HRQoL outcomes at both weeks 12 and 24. By week 24, mean change differences (95% confidence interval) between the arms were significant for GHS/QoL (4.9 [0.9, 9.0]), physical functioning (3.8 [0.8, 6.7]), diarrhea (−6.2 [−10.0, −2.5]), fatigue (−4.5 [−8.9, −0.1]), and nausea/vomiting (−4.5 [−8.9, −0.1]); role functioning (4.8 [−0.2, 9.7]) was marginally better in the zanubrutinib arm and there were no differences in pain symptoms (−0.4 [−4.3, 5.1]) between the arms.

Conclusions

During the first 24 weeks of treatment, zanubrutinib was associated with better HRQoL outcomes in patients with treatment-naive CLL/SLL without del(17p) compared to BR.

Trial registration

The SEQUOIA trial is registered on clinicaltrials.gov as SEQUOIA trial (NCT03336333).

Keywords:

• Zanubrutinib
• bendamustine
• rituximab
• SEQUOIA
• health-related quality-of-life
• patient-reported outcomes
• chronic lymphocytic leukemia
• small cell lymphocytic lymphoma

Transparency

 

Declaration of funding

This study was funded by BeiGene, LTD.

Declaration of financial/other relationships

Consultant/Advisor: Paolo Ghia: Advisory boards and consultancy fees from AbbVie, AstraZenenca, BMS, BeiGene, Janssen, Lilly/Loxo Oncology, MSD, Roche; Tadeusz Robak: BeiGene Participation in advisory board; Jennifer R. Brown: AbbVie, Acerta/AstraZeneca, Alloplex Biotherapeutics, BeiGene, Genentech/Roche, Grifols Worldwide Operations, iOnctura, Kite, Merck, Numab Therapeutics, Pfizer, Pharmacyclics; Brad S. Kahl: AbbVie, AstraZeneca, BeiGene, Genentech, Lilly, Janssen, Novartis, Seattle Genetics, Kite; Mazyar Shadman: AbbVie, Genentech, AstraZeneca, Pharmacyclics, BeiGene, BMS, MorphoSys/Incyte, Kite, Eli Lilly, Genmab, Mustang Bio, Regeneron, ADC therapeutics, Fate Therapeutics, Nurix and MEI Pharma.

Stock/Shareholder: Gisoo Barnes, Keri Yang, Tian Tian, Andy Szeto, and Jason C. Paik: BeiGene.

Other: Gisoo Barnes, Keri Yang, Tian Tian, Andy Szeto, and Jason C. Paik: Employees of BeiGene; Constantine S. Tam: Honorarium from AbbVie, Janssen, BeiGene, LOXO and Roche; Mazyar Shadman: Participation on a Data Safety Monitoring Board or Advisory Board for Fate Therapeutics and BeiGene. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Ghia, Tam, Tadeusz, Brown, Kahl, Robak, Shadman, and Barnes were responsible for the study design and data collection. Barnes, Yang, Tian, Szeto, and Paik were responsible for data interpretation and reviewing drafts of the manuscript. Barnes and Tian were responsible for data analysis. All authors contributed to the review and editing of the manuscript.

Acknowledgements

The authors wish to acknowledge the investigative centers’ study staff and study patients and to recognize those from BeiGene, Ltd. who have substantially contributed to the development of this manuscript. Editorial assistance was provided by Jason C. Allaire, PhD (Generativity – Health Economics and Outcomes Research, Durham, NC). This assistance was funded by BeiGene, Ltd.

Data availability statement

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Ethics statement

This protocol was approved by the ethics committees of the participating sites. The study was performed according to the ethical principles of the Declaration of Helsinki, Good Clinical Practice guidelines, and the requirements of the public registration of clinical trials.

Written informed consent was obtained prior to participation in the study.