Real-World Pharmacokinetic and Exposure-Response Characterization of Venetoclax in Chinese Patients with Hematological Malignancies.

INTRODUCTION

Post-marketing evaluation of lower-dose regimens is critical for optimizing individualized oncology therapy. Venetoclax (VNX) is approved for the treatment of hematological malignancies at doses of ≥400 mg once daily following a ramp-up schedule. However, favorable clinical responses have been observed in Chinese patients receiving lower doses (≤200 mg/day), prompting further investigation.

METHODS

A prospective, non-interventional, real-world study was conducted in 76 Chinese patients, yielding 121 plasma samples. Published population pharmacokinetic (PopPK) models, primarily developed in Caucasian populations, were applied for external model-based comparisons of VNX exposure between Chinese patients and previously reported Caucasian populations. A new PopPK model was developed for the Chinese population, followed by exposure-response analysis to assess the relationship between VNX dose and therapeutic efficacy.

RESULTS

External model evaluation demonstrated higher VNX exposure in Chinese patients compared with Caucasian populations. The newly developed Chinese PopPK model estimated apparent clearance at 7.33 L/h, substantially lower than previously reported values in Caucasian patients (15-19.54 L/h). Exposure-response analysis indicated that VNX at 200 mg/day achieved optimal therapeutic efficacy in combination therapy, with minimal incremental benefit observed at higher doses.

CONCLUSION

Significant ethnic differences in VNX pharmacokinetics were identified. These findings support the clinical effectiveness of lower-dose (200 mg/day) VNX-based regimens in Chinese patients and highlight the importance of population-specific dose optimization.