Predictive and prognostic biomarkers in the era of new targeted therapies for chronic lymphocytic leukemia.

Treatment options for chronic lymphocytic leukemia (CLL) have improved with the introduction of the B-cell receptor inhibitors ibrutinib and idelalisib, and of the BCL2 inhibitor venetoclax. While awaiting the results of head to head comparisons between novel agents and chemoimmunotherapy, predictive biomarkers can assist physicians in treatment tailoring. Though novel agents have modified the landscape of predictors at the time of treatment requirement, the usefulness of historical CLL prognostic biomarkers is still up-to-date when considering anticipation of time to first treatment. This review discusses: (i) disease-related (TP53 defects, immunoglobulin gene mutations), therapy-related (duration of remission), and patient-related (age, comorbidities) biomarkers that can be used in the clinical practice to inform CLL treatment decision either at the time of first line therapy and disease relapse; and (ii) the need of new biomarkers to re-define high-risk CLL because of the questioning by novel agents of historical prognostic factors.