Journal article

Exposure–response analysis of venetoclax in combination with rituximab in patients with relapsed or refractory chronic lymphocytic leukemia: pooled results from a phase 1b study and the phase 3 MURANO study

R Deng, L Gibiansky, T Lu, X Li, D Lu, C Li, S Girish, J Wang, M Boyer, N Shankar, K Humphrey, KJ Freise, AH Salem, JF Seymour, AP Kater, D Miles

Leukemia and Lymphoma | TAYLOR & FRANCIS LTD | Published : 2020

Abstract

Exposure–response relationships from a phase 1b (M13-365) and phase 3 (MURANO) study were investigated to assess benefit/risk of venetoclax 400 mg daily plus rituximab in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Dose intensities were summarized by tertiles of predicted venetoclax steady-state average concentrations based on nominal venetoclax dose (CmeanSS,nominal) for tolerability; exposure–safety analyses used logistic regression. Exposure–progression-free survival (PFS) relationships were assessed using MURANO data, with CmeanSS,nominal as a grouping factor. Covariates were demographics, geographic region, study, baseline disease characteristics, ECOG performance stat..

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Funding Acknowledgements

The authors thank the patients, enrolling physicians, site staff, and venetoclax study teams. The authors also thank Dr Mehrdad Mobasher for his valuable contributions to the manuscript. Third-party medical writing assistance was provided by Christopher Dunn and Andrew Sutton of GardinerCaldwell Communications, and was funded by F. Hoffmann - La Roche Ltd.