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Identification of Predictive Biomarkers Based on Cytokine Profiles for Molecular Relapse After Treatment-Free
Bianca Vasconcelos Cordoba1, Carolina Pavlovsky2, María Belén Sanchez1
1Centro de Investigaciones Oncológicas-Fundación Cáncer (CIO-FUCA), Buenos Aires 1426, Argentina.
Abstract:
Tyrosine kinase inhibitors (TKIs) have transformed chronic myeloid leukemia (CML) into a manageable disease, and discontinuation has become a feasible goal for many patients. However, molecular relapse after TKI cessation remains a challenge. This study investigated factors influencing molecular relapse-free survival (MRFS) in a real-world cohort of CML patients undergoing TKI discontinuation, focusing on clinical, molecular, and immune-related variables. Traditional prognostic tools, such as the Sokal score, showed limited capacity to predict relapse risk in this context. Instead, total treatment duration and depth of molecular response emerged as critical predictors, with longer therapy and deeper remission associated with improved outcomes. A key novel finding was the prognostic relevance of cytokine profiles, particularly interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1). These cytokines were strong predictors of relapse in a decision tree model that achieved high specificity and positive predictive value in an independent validation cohort. Notably, lower IL-6 and MCP-1 levels were associated with increased relapse risk, suggesting reduced immune surveillance may contribute to recurrence. Integrating cytokine signatures with molecular markers improved prognostic accuracy, supporting immune biomarkers as complements to established clinical parameters. These findings underscore the complexity of relapse mechanisms and the need for individualized risk assessment when considering TKI discontinuation.
Insights
Molecular relapse after tyrosine kinase inhibitor (TKI) cessation in chronic myeloid leukemia (CML) is a challenge. Novel cytokine profiles, like IL-6 and MCP-1, alongside treatment duration and response depth, predict relapse risk.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Tyrosine kinase inhibitors (TKIs) have improved chronic myeloid leukemia (CML) management.
- TKI discontinuation is a goal for many CML patients, but molecular relapse remains a significant challenge.
- Predicting relapse risk after TKI cessation requires refined prognostic tools.
Purpose of the Study:
- To investigate factors influencing molecular relapse-free survival (MRFS) in CML patients discontinuing TKIs.
- To evaluate clinical, molecular, and immune-related variables for predicting relapse.
- To identify novel biomarkers for assessing relapse risk.
Main Methods:
- Analysis of a real-world cohort of CML patients undergoing TKI discontinuation.
- Assessment of traditional prognostic scores (e.g., Sokal score).
- Evaluation of cytokine profiles (IL-6, MCP-1) and molecular markers.
- Development and validation of a decision tree model incorporating cytokine signatures.
Main Results:
- Traditional prognostic tools had limited predictive capacity for relapse.
- Total treatment duration and depth of molecular response were critical predictors of MRFS.
- Cytokine profiles, specifically IL-6 and MCP-1 levels, were significant predictors of relapse.
- Lower IL-6 and MCP-1 levels correlated with increased relapse risk, suggesting impaired immune surveillance.
- Integrating cytokine signatures with molecular markers enhanced prognostic accuracy.
Conclusions:
- Cytokine profiles offer novel prognostic value for predicting molecular relapse after TKI discontinuation in CML.
- Immune biomarkers, such as IL-6 and MCP-1, can complement established clinical parameters for risk stratification.
- Individualized risk assessment is crucial for optimizing TKI discontinuation strategies in CML.
