Relevance of Prognostic Factors in the Era of Targeted Therapies in CLL

Abstract

Purpose of review: Clinicians continue to utilize prognostic biomarkers, such as expression of CD38 and ZAP-70, IGHV mutational status, cytogenetic abnormalities, and genomic aberrations in TP53, to guide prognosis and treatment of patients with CLL. These biomarkers have been validated with standard chemoimmunotherapy. Here, we discuss whether these biomarkers maintain their prognostic significance in the era of targeted therapy.

Recent findings: Multiple phase 3 clinical trials have now proven improved efficacy of targeted therapy over traditional chemoimmunotherapy. We now have ample prospective data using targeted therapy to critically evaluate whether prior prognostic biomarkers remain relevant. High-risk features do not have the same magnitude of effect on clinical outcomes in the era of targeted therapy when compared to chemoimmunotherapy. Aberrations in TP53 continue to predict inferior outcomes. More research is needed to determine what features confer poor prognosis when targeted therapy is used to treat CLL.

Keywords: Biomarkers; CLL; Chronic lymphocytic leukemia; Prognosis; Targeted therapy.