From Biomarkers to Models in the Changing Landscape of Chronic Lymphocytic Leukemia: Evolve or Become Extinct

SIMPLE SUMMARY: Chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. Thus, predicting the outcome of patients with this disease is a topic of special interest. The rapidly changing treatment landscape of CLL has questioned the value of classical biomarkers and prognostic models. Herein we examine the current state-of-the-art of prognostic and predictive biomarkers in the setting of new oral targeted agents with special focus on the most controversial findings over the last years. We also discuss the available information on the role of “old” and “new” prognostic models in the era of oral small molecules. ABSTRACT: 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.