2ⁿᵈ Edition of the Cancer R&D World Conference 2026

Abstract

Imatinib remains the frontline therapy for Chronic Myeloid Leukemia (CML); however, resistance continues to challenge long-term patient outcomes. Conventional monitoring based on BCR-ABL1 transcript levels detects resistance only after approximately 3 months of therapy, leaving a critical gap during which treatment failure progresses unnoticed. A diagnostic tool capable of predicting non-responders at the time of diagnosis would significantly improve early decision-making. This study investigates whether an ex vivo PBMC-based proliferation assay performed at baseline can serve as an early indicator of imatinib resistance. Forty-five newly diagnosed CML patients were recruited. Baseline BCR-ABL1 IS% values were available for 42 patients, and PBMCs were successfully isolated from 30 individuals. Follow-up molecular response data at three months were obtained from 15 patients; 6 were clinically resistant, and 9 were sensitive to therapy.

PBMCs collected at diagnosis were exposed ex vivo to two imatinib concentrations (5000 and 10,000 nM) to assess proliferation inhibition. Ex vivo classifications were compared with clinical outcomes to evaluate predictive performance. Based on the ex vivo proliferation profile, 5 patients were predicted to be resistant and 10 to be sensitive. Concordance between ex vivo predictions and three-month clinical outcomes was remarkably high, with 14 of 15 patients showing matched results. Only one patient displayed discordance. Statistical analysis demonstrated a strong association between ex vivo-identified resistance and clinical resistance (χ² = 11.25, p = 0.0008; Fisher’s exact p = 0.002).

The assay exhibited excellent predictive ability, yielding an AUC of 0.91. The ex vivo PBMC proliferation assay shows great promise as a quick, reliable way to predict imatinib resistance at diagnosis. Its strong alignment with three-month molecular results emphasizes its potential as an early diagnostic tool. Adding this assay into clinical routines could enable timely treatment adjustments, enhance risk assessment, and support more personalized treatment plans for patients with CML.