Predicting treatment-free remission outcomes in Chronic Myeloid Leukemia patients using an integrated model of tumor-immune dynamics

Abstract

The interactions between tumor and the immune system are main factors in determining cancer treatment outcomes. In Chronic Myeloid Leukemia (CML), considerable evidence shows that the dynamics between residual leukemia and the patients immune system can result in either sustained disease control, leading to treatment-free remission (TFR), or disease recurrence. The question remains how to integrate mechanistic and data-driven models to support prediction of treatment outcomes. Starting from classical ecological modeling concepts, which allow to explicitly account for immune interactions at the cellular level, we incorporate time-course data on natural killer (NK) cell number, function, and their tumor-induced suppression into our general model of CML treatment. We identify relevant time scales governing treatment and immune response, enabling refined model calibration using tumor and NK cell time courses from different datasets. While the model successfully describes patient-specific response dynamics, critical parameters for predicting treatment outcome remain uncertain. However, by explicitly incorporating tumor load changes in response to TKI dose alterations, these parameters can be estimated and used to derive model predictions for treatment cessation. Further exploring dynamic changes in the number of functional immune cells, we suggest specific measurement strategies of immune effector cell populations to enhance prediction accuracy for CML recurrence following treatment cessation. The generalizability and flexibility of our approach represent a significant step towards quantitative, personalized medicine that integrates tumor-immune dynamics to guide clinical decisions and optimize dynamic cancer therapies.