Real-world time to discontinuation of first-line venetoclax + obinutuzumab in chronic lymphocytic leukemia/small lymphocytic lymphoma

Abstract

Objective

To evaluate the time to discontinuation (TTD) and baseline characteristics among patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) treated with first-line (1L) venetoclax + obinutuzumab (VO) in the United States.

Methods

A nationwide electronic health record-derived database was used to select adults with CLL/SLL initiating a 1L venetoclax-based regimen between April 11, 2016–July 31, 2020. Study measures included TTD (defined as >120-day treatment gap or switching therapy) and baseline characteristics by discontinuation status.

Results

A total of 113 patients receiving 1L VO on/before July 31, 2020 were eligible for analysis (mean age: 65.9 years; 31.9% women). During the first 60 days post-treatment initiation, 3.5% had tumor lysis syndrome (TLS). The proportion of patients using corticosteroids, anti-hyperuricemics, and anti-emetics was higher during the first 60 days post-treatment initiation (100.0%, 78.8%, and 52.2%, respectively) than the period from day 61 onward (67.0%, 45.5%, and 33.9%, respectively). Mean (median) duration of active treatment was 11.6 (12.1) months; 16.8% discontinued treatment before completing 12 cycles, 68.1% completed ≥12 cycles (among which 29.9% completed ≥15 cycles), and 15.0% who did not discontinue treatment were censored before completing 12 cycles. Kaplan-Meier analysis showed that median TTD was 13.8 months. Relative to those completing ≥12 cycles, patients discontinuing treatment before completing the prescribed 12 cycles were older (70.4 vs. 65.1 years) and had poorer renal function (36.8% vs. 13.0% with creatinine clearance <60 mL/min).

Conclusion

A small proportion of CLL/SLL patients who were older and had poorer baseline renal function discontinued 1L VO prior to completing 12 treatment cycles. Additionally, treatment utilization, including medications related to TLS mitigation and management, was more intense during the initiation phase of VO. Further research with longer follow-up to assess long-term outcomes of VO treatment after early discontinuation is warranted.

Keywords:

• Venetoclax
• obinituzumab
• chronic lymphocytic leukemia
• tumor lysis syndrome
• time to discontinuation
• retrospective study

Transparency

Declaration of funding

This study was funded by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design; data collection, analysis, and interpretation; manuscript writing; and the decision to publish the article.

Declaration of financial/other relationships

XL, ZPQ, and QH are employees of Janssen Scientific Affairs, LLC and stockholders of Johnson & Johnson. LHW was an employee of Janssen Scientific Affairs, LLC at the time the study was conducted. BE, AH, MHL, and PL are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC. KAR has received research funding from Genentech, AbbVie, Novartis, and Janssen (not for the present study); consulting fees from Acerta Pharma, AstraZeneca, Innate Pharma, Pharmacyclics, Genentech, and AbbVie; and travel funding from AstraZeneca. SPF and SL were employees of Analysis Group, Inc. at the time the study was conducted.

A reviewer on this manuscript declared that they have received consulting fees with AbbVie, Janssen, BeiGene, and Astrazeneca. Peer reviewers on this manuscript have received an honorarium from CMRO for their review work but have no other relevant financial relationships to disclose.

Author contributions

XL: Conceptualization, investigation, methodology, project administration, resources, supervision, validation, visualization, writing – original draft, writing – review & editing. BE, MHL, and PL: Conceptualization, data curation, formal analysis, investigation, methodology, project administration, resources, software, supervision, validation, visualization, writing – original draft, writing – review & editing. ZPQ: Investigation, methodology, project administration, supervision, validation, visualization, writing – review & editing. LHW: Investigation, methodology, validation, visualization, writing – review & editing. SPF, AH, and SL: Data curation, formal analysis, investigation, methodology, software, supervision, validation, visualization, writing – original draft, writing – review & editing. QH: Conceptualization, funding acquisition, investigation, methodology, project administration, resources, supervision, validation, visualization, writing – review & editing. KAR: Conceptualization, investigation, methodology, supervision, validation, visualization, writing – review & editing

Acknowledgements

Medical writing assistance was provided by Flora Chik, PhD, MWC, an employee of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC, which funded the development and conduct of this study and manuscript.

Data availability statement

The data that support the findings of this study have been originated by Flatiron Health, Inc. Requests for data sharing by license or by permission for the specific purpose of replicating results in this manuscript can be submitted to [email protected].

Ethical approval

The data were de-identified and subject to obligations to prevent re-identification and protect patient confidentiality. Institutional Review Board approval of the Flatiron’s protocol was obtained prior to study conduct and included a waiver of informed consent.

Previous presentation

Part of the material in this manuscript was presented as a poster at the NCCN 2022 Annual Conference held on March 31–April 2, 2022 in Orlando, FL.