The evolving landscape of chronic lymphocytic leukemia on diagnosis, prognosis and treatment

© 2021 by the authors. The knowledge of chronic lymphocytic leukemia (CLL) has progressively deepened during the last forty years. Research activities and clinical studies have been remarkably fruitful in novel findings elucidating multiple aspects of the pathogenesis of the disease, improving CLL diagnosis, prognosis and treatment. Whereas the diagnostic criteria for CLL have not substantially changed over time, prognostication has experienced an expansion with the identification of new biological and genetic biomarkers. Thanks to next-generation sequencing (NGS), an unprecedented number of gene mutations were identified with potential prognostic and predictive value in the 2010s, although significant work on their validation is still required before they can be used in a routine clinical setting. In terms of treatment, there has been an impressive explosion of new approaches based on targeted therapies for CLL patients during the last decade. In this current chemotherapy-free era, BCR and BCL2 inhibitors have changed the management of CLL patients and clearly improved their prognosis and quality of life. In this review, we provide an overview of these novel advances, as well as point out questions that should be further addressed to continue improving the outcomes of patients. This research was funded by grants from the Spanish Fondo de Investigaciones Sanitarias PI15/01471 and PI18/01500, Instituto de Salud Carlos III (ISCIII), European Regional Development Fund (ERDF) “Una manera de hacer Europa”, “Consejería de Educación, Junta de Castilla y León” (SA271P18 and SA118P20), “Proyectos de Investigación del SACYL”, Spain GRS1847/A/18 and GRS1653/A17, “Fundación Memoria Don Samuel Solórzano Barruso” (FS/23-2018, FS/33-2020), “Programa de financiación de grupos de investigación” (PIC2-2020-25) and by grants (RD12/0036/0069) from Red Temática de Investigación Cooperativa en Cáncer (RTICC), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC CB16/12/00233) and SYNtherapy “Synthetic Lethality for Personalized Therapy-based Stratification In Acute Leukemia” (ERAPERMED2018-275); ISCIII (AC18/00093). M.Q.-Á. was fully supported by an “Ayuda predoctoral de la Junta de Castilla y León” by Fondo Social Europeo (JCYL-EDU/529/2017 PhD scholarship) and now holds a FEHH (“Fundación Española de Hematología y Hemoterapia”); C.P.-C. was supported by an “Ayuda predoctoral en Oncología” (AECC) and is a recipient of a PFIS grant (FI19/00191) from Instituto de Salud Carlos III; M.H.-S. was supported by a grant from FEHH/Janssen (“Sociedad Española de Hematología y Hemoterapia”) and now holds a Sara Borrell post-doctoral contract (CD19/00222) from the Instituto de Salud Carlos III (ISCIII). The PFIS grant and Sara Borrell posdoctoral contract are co-founded by Fondo Social Europeo (FSE) “El Fondo Social Europeo invierte en tu futuro”; A.E.R.-V. was supported with a research grant by FEHH (“Fundación Española de Hematología y Hemoterapia”).