# Venetoclax concentration affects the incidence of haematological adverse events in patients with acute myeloid leukaemia

## TL;DR

Higher Venetoclax concentrations in patients with acute myeloid leukemia increase the risk of severe blood-related side effects.

## Contribution

The study identifies Venetoclax Cmax as a key predictor for severe hematological adverse events.

## Key findings

- VEN + PCZ and VEN + VCZ groups had higher VEN concentrations than other groups.
- Increased VEN concentration correlated with higher incidence of Grade 3 or higher haematological AEs.
- A VEN Cmax of 4,886.00 ng/mL best predicted and mitigated severe AEs.

## Abstract

Venetoclax (VEN) demonstrates considerable inter-individual variability in drug exposure, and its pharmacokinetics are substantially influenced by concurrent administration of CYP3A inhibitors. This study explores the relationship between VEN exposure and the incidence of haematological adverse events (AEs) in patients by quantifying systemic VEN concentrations.

We retrospectively analyzed data from 114 patients who received VEN therapy. Among these, 52 were treated with VEN combined with azacitidine (AZA, days 1–7), 20 received VEN + AZA combined with omeprazole (OPZ), 20 received VEN + AZA combined with voriconazole (VCZ), and 22 received VEN + AZA combined with posaconazole (PCZ). High-performance liquid chromatography was used to determine the plasma steady-state Cmin and Cmax of VEN (n = 114), and the plasma steady-state Cmin of VCZ (n = 20) and PCZ (n = 22).

The effect of combined medication on VEN concentration was as follows: VEN + PCZ group/VEN + VCZ group > VEN + OPZ group > VEN group. Increased VEN concentration increased the incidence of Grade 3 or higher haematological AEs. CYP3A inhibitors increased VEN levels, thereby increasing the risk of AEs. A VEN Cmax value of 4,886.00 ng/mL had the highest predictive value for mitigating AEs in patients presenting with Grade ≥3 neutropenia and thrombocytopenia.

VEN concentration is correlated with the occurrence of haematological AEs, and VEN concentrations can be used to predict the occurrence of haematological AEs.

Diagram illustrating a study on Venetoclax (VEN) concentration affecting hematological adverse events in acute myeloid leukemia patients. It includes chemical structures of VEN and AZA, dosage details, patient groups, and treatment outcomes like neutropenia and platelet reduction. Results show Cmin and Cmax measurements with two graphs plotting specificity versus one minus specificity, and a conclusion that Cmax is the best predictor for reducing adverse events in patients with Grade 3 or higher platelet and thrombocytopenia.