Chronic Lymphocytic Leukemia: Evolving Management With New Data From EHA 2025 - Episode 1
Defining High-Risk Disease in CLL—Biomarkers and Baseline Testing
Panelists discuss how proper baseline testing, including cytogenetics, TP53 mutation status, and IGHV mutation testing, is essential for risk stratification and treatment selection in patients with chronic lymphocytic leukemia (CLL), with TP53 disruption being the most critical prognostic factor that typically directs clinicians toward continuous Bruton tyrosine kinase (BTK) inhibitor therapy.
Defining High-Risk Disease in CLL—Biomarkers and Baseline Testing
This educational segment focuses on the critical importance of comprehensive biomarker testing in patients with CLL before initiating treatment. The discussion emphasizes that although numerous treatment options are available in 2025, proper patient testing is essential to understand disease biology and inform therapeutic selection in the frontline setting. The panel of hematology experts highlights how key prognostic tests can help predict patient responses to therapy and guide treatment decisions.
The essential testing panel includes several distinct components that provide complementary information about disease characteristics. Cytogenetics testing serves as the foundational assessment, including fluorescence in situ hybridization (FISH) testing and stimulated karyotype testing to detect complex karyotype abnormalities. Molecular testing specifically targets TP53 mutations, requiring a separate test from FISH analysis that only detects 17p deletions. The IGVH mutation status test determines whether patients have mutated (favorable prognosis) or unmutated (less favorable prognosis) disease. Additional supportive tests include β2-microglobulin levels, which contribute to overall prognostic assessment.
The clinical significance of these biomarkers has evolved in the novel agent era, with experts noting that even high-risk patients are achieving better outcomes with current therapies. However, TP53 disruption status remains the most critical prognostic factor, typically directing treatment toward continuous BTK inhibitor therapy rather than time-limited approaches. Although unmutated IGVH status still represents a less favorable prognostic feature, patients with this marker can achieve good outcomes with appropriate treatment selection. The highest-risk patients continue to be those with TP53 disruption and complex karyotype, requiring specialized treatment approaches with continuous BTK inhibitor–based regimens for optimal outcomes.
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