Clinical Validation of Venetoclax Volumetric Microsampling in Patients with Leukemia with Assessment of Whole-Blood-to-Plasma Conversion Strategies and Self-Microsampling Feasibility.

BACKGROUND AND

OBJECTIVE

Venetoclax shows substantial pharmacokinetic (PK) variability and frequent toxicity, making it an archetypal candidate for PK monitoring. Capillary microsampling may facilitate decentralized PK monitoring of venetoclax. However, clinical validation is lacking. This study aimed to clinically validate capillary microsampling for venetoclax and to assess the feasibility of home-based self-microsampling.

METHODS

Adult patients with acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) receiving oral venetoclax therapy provided paired venous plasma and capillary samples using dried blood spot (DBS) and volumetric absorptive microsampling (VAMS) devices. We evaluated individualized hematocrit-based microsample-to-plasma correction models and previously published whole-blood-to-plasma conversion strategies. Agreement and predictive performance were assessed according to international microsampling validation criteria. The feasibility of home-based self-microsampling was evaluated by examining patients' ability to collect samples independently, the proportion of usable returned samples, and device usability.

RESULTS

A total of 25 patients contributed 64 sets of paired venous plasma, DBS, and VAMS samples. Uncorrected DBS and VAMS venetoclax concentrations underestimated plasma concentrations (mean bias - 21% and - 14%, respectively) and showed clear hematocrit dependence. Individualized hematocrit-plasma/microsample ratio models showed excellent performance, with 95% of DBS and 91% of VAMS concentrations within ± 20% of plasma and low bias and imprecision across all validation metrics. Literature-based correction strategies showed lower acceptance rates and wider limits of agreement. Among patients attempting self-microsampling, 18 of 21 sampled independently, 76% of returned DBS/VAMS samples were suitable for analysis, and usability ratings were higher for VAMS than DBS.

CONCLUSIONS

Capillary microsampling enables accurate venetoclax quantification in patients with AML and CLL when individualized hematocrit-based microsample-to-plasma conversion is applied. Both DBS and VAMS met international validation criteria, and home-based self-microsampling proved feasible. Venetoclax home-based self-microsampling warrants further study as a tool for decentralized PK monitoring.