Exposure-response evaluations of venetoclax efficacy and safety in patients with non-Hodgkin lymphoma

Abstract

Exposure-response analyses were performed for a venetoclax monotherapy study in 106 patients with varying subtypes of non-Hodgkin lymphoma (NHL) (NCT01328626). Logistic regression, time-to-event, and progression-free survival (PFS) analyses were used to evaluate the relationship between venetoclax exposure, NHL subtype and response, PFS, or occurrence of serious adverse events. Trends for small increases in the probability of response with increasing venetoclax exposures were identified, and became more evident when assessed by NHL subtype. Trends in exposure-PFS were shown for the mantle cell lymphoma (MCL) subtype, but not other subtypes. There was no increase in the probability of experiencing a serious adverse event with increasing exposure. Overall, the results indicate that venetoclax doses of 800–1200 mg as a single agent may be appropriate to maximize efficacy in MCL, follicular lymphoma, and diffuse large B-cell lymphoma subtypes with no expected negative impact on safety.

Keywords:

• Venetoclax
• pharmacokinetics
• exposure-response
• non-Hodgkin lymphoma
• PFS
• objective response

Acknowledgements

The authors thank AbbVie employees Sandhya Sankar and Subba Madala for preparing the datasets and Allison Kitten for medical writing support.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1361024.

Disclosure statement

AP, SG, KF, MV, RM, SM, and AHS are employees of AbbVie and may own stock.

Additional information

Funding

This analysis was supported by AbbVie in collaboration with Genentech/Roche. Venetoclax (ABT-199/GDC-0199) is being developed in collaboration between AbbVie and Genentech. AbbVie and Genentech provided financial support for the study that is included in the analysis and participated in the design, study conduct, analysis and interpretation of data as well as the writing, review, and approval of the manuscript.