Health-related quality of life outcomes associated with zanubrutinib versus ibrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma: results from the ALPINE Trial

Abstract

Objective

The purpose of this analysis was to assess health-related quality of life (HRQoL) in patients treated with zanubrutinib and ibrutinib in the ALPINE trial (NCT03734016).

Methods

HRQoL was measured by the EORTC QLQ-C30 and EQ-5D-5L at baseline, cycle 1, and every third cycle until the end of treatment. Key patient-reported outcome (PRO) endpoints included global health status (GHS), physical and role functioning, as well as symptoms of fatigue, pain, diarrhea, and nausea/vomiting. A mixed model repeated-measure analysis using key PRO endpoints at key clinical cycles (cycles 7 and 13) was performed.

Results

652 patients were randomized to receive zanubrutinib (n = 327) or ibrutinib (n = 325). By cycle 7, GHS scores improved with zanubrutinib versus ibrutinib, and in cycle 13, GHS scores remained higher in the zanubrutinib arm. The zanubrutinib arm experienced clinically meaningful improvements in physical and role functioning, as well as pain and fatigue symptoms at both cycles. Patients in the zanubrutinib arm reported lower diarrhea scores. Nausea/vomiting scores maintained in both arms. EQ-VAS scores showed greater improvement from baseline at both cycle 7 (7.92 versus 3.44) and cycle 13 (7.75 versus 3.92) of treatment with zanubrutinib compared to ibrutinib, respectively.

Conclusions

Patients with R/R CLL/SLL treated with zanubrutinib demonstrated improvement versus ibrutinib in the GHS scale at cycle 7. Other endpoints continued to improve, suggesting treatment with zanubrutinib positively affected HRQoL over time. Given the generally good HRQoL at baseline in both arms, the differences between the arms were not significant.

Keywords:

• Zanubrutinib
• ibrutinib
• ALPINE
• health-related quality of life
• patient-reported outcomes
• chronic lymphocytic leukemia
• small cell lymphocytic lymphoma

Trial registration:

• The ALPINE trial is registered on clinicaltrials.gov as ALPINE trial (BGB-3111-305
• NCT03734016)

Transparency

Disclosure of financial/other relationships

PH received honoraria from Janssen, AbbVie, and Roche and received travel funds from Janssen and AbbVie. JB has served as a consultant for AbbVie, Acerta/AstraZeneca, BeiGene, Bristol Myers Squibb/Juno/Celgene, Catapult, Eli Lilly, Genentech/Roche, Janssen, MEI Pharma, MorphoSys AG, Nextcea, Novartis, Pfizer, and Rigel. NL received research funding from Loxo Oncology, Juno, Oncternal, Verastem, TG Therapeutics, MingSight, and Octapharma and has been in a consulting role for AbbVie, AstraZeneca, BeiGene, Genentech, Celgene, Gilead, Janssen, and Pharmacyclics. SO has served as a consultant for AbbVie, Alexion, Amgen, Aptose Biosciences, Astellas, AstraZeneca, Autolus, Bristol Myers Squibb, Celgene, DynaMed, Eli Lilly and Company, Gilead, GlaxoSmithKline, Janssen Oncology, Johnson and Johnson, Juno Therapeutics, MEI Pharma, Inc., Merck, NOVA Research, Pfizer, Pharmacyclics, TG Therapeutics, Vaniam, Verastem, and Vida Ventures and received research funding from Acerta, Alliance, BeiGene, Ltd, Caribou Biosciences, Inc., Gilead, Kite, Loxo Oncology, Inc., Mustang, Nurix Therapeutics, Inc., Pfizer, Pharmacyclics, Regeneron Pharmaceuticals, and TG Therapeutics. CST received research funding from Janssen and AbbVie and received honoraria from Janssen, AbbVie, BeiGene, Novartis, and Roche. KY, GB, and KW are employees of BeiGene and may own company stock/stock options. BE has served as a consultant for Janssen, Roche, Novartis, AbbVie, Gilead, Celgene, ArQule, AstraZeneca, Oxford Biomedica (UK), and BeiGene; has served on the speaker’s bureaus for Janssen, Gilead, Roche, AbbVie, Novartis, Celgene, Adaptive Biotechnologies, BioGene, and AstraZeneca; received research funding from Janssen, Gilead, Roche, AbbVie, BeiGene, and AstraZeneca; and received travel funds from Janssen, Roche, Novartis, AbbVie, Gilead, and Celgene. The other authors declare no competing interests.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

JB, CT, NL, SO, LQ, BE, GB were responsible for study design and data collection. All authors were responsible for data interpretation and reviewing and approving drafts of the manuscript. KW and GB were responsible for data analysis. KY, GB, TS, KW were responsible for data interpretation.

Acknowledgements

Editorial assistance was provided by Jason C. Allaire, PhD, of Generativity Solutions Group. 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.

Additional information

Funding

This study was funded by BeiGene, LTD.