%0 Journal Article %T Chronic Lymphocytic Leukemia: Prognostic Factors in the Era of Novel Drugs. %A Urso A %A Martino EA %A Cuneo A %A Gentile M %A Rigolin GM %J Cancers (Basel) %V 16 %N 15 %D 2024 Jul 31 %M 39123460 %F 6.575 %R 10.3390/cancers16152732 %X Novel drugs have profoundly changed the outcomes in chronic lymphocytic leukemia (CLL) patients, and the traditional prognostic factors that were identified in the era of chemoimmunotherapy need to be validated in the context of these new targeted therapies. Currently, the most important prognostic genetic biomarkers are the immunoglobulin heavy chain variable (IGHV) mutational status, genetic aberrations including del(17p)/TP53 abnormalities, and the complex karyotype. In this review, we discuss the prognostic role of these genomic markers in relation to novel treatments. Moreover, we present and discuss new scoring systems that were elaborated and validated in the era of new drugs. In routine clinical practice, the application of an extensive genomic work-up with validated prognostic markers could improve the identification of "very high-risk" CLL patients who could benefit from novel, more effective targeted treatments.