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. Keywords: venetoclax, hematological malignancy, exposure-response, therapeutic drug monitoring