From biomarkers to models in the changing landscape of chronic lymphocytic leukemia: Evolve or become extinct

© 2021 by the authors.Chronic lymphocytic leukemia (CLL) is an extremely heterogeneous disease. With the advent of oral targeted agents (Tas) the treatment of CLL has undergone a revolution, which has been accompanied by an improvement in patient’s survival and quality of life. This paradigm shift also affects the value of prognostic and predictive biomarkers and prognostic models, most of them inherited from the chemoimmunotherapy era but with a different behavior with Tas. This review discusses: (i) the role of the most relevant prognostic and predictive biomarkers in the setting of Tas; and (ii) the validity of classic and new scoring systems in the context of Tas. In addition, a critical point of view about predictive biomarkers with special emphasis on 11q deletion, novel resistance mutations, TP53 abnormalities, IGHV mutational status, complex karyotype and NOTCH1 mutations is stated. We also go over prognostic models in early stage CLL such as IPS-E. Finally, we provide an overview of the applicability of the CLL-IPI for patients treated with Tas, as well as the emergence of new models, generated with data from patients treated with Tas.This research was funded by grants from the Spanish Fondo de Investigaciones Sanitarias PI15/01471, 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, SA118P20), “Proyectos de Investigación del SACYL”, Spain GRS 1847/A/18,GRS1653/A17,“Fundación Memoria Don Samuel Solórzano Barruso” (FS/23-2018, FS/33-2020), 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 the Fondo Social Europeo (JCYL-EDU/529/2017 PhD scholarship) and is now a recipient of FEHH (“Fundación Española de Hematología y Hemoterapia”); C.P.C. was supported by an “Ayuda predoctoral en Oncología” (Asociación Española contra el Cáncer) and is a recipient of a PFIS grant (FI19/00191) from Instituto de Salud Carlos III (ISCiii); 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 ISCiii. PFIS grant and Sara Borrell postdoctoral contract are co-founded by Fondo Social Europeo (FSE) “El Fondo Social Europeo invierte en tu futuro”; A.E.R.V. is supported with a research grant by FEHH (“Fundación Española de Hematología y Hemoterapia”)