The general aim of the project is the identification of dynamic molecular markers that can help the early and real time prediction of sustained benefit or no benefit from ibrutinib treatment in CLL harboring TP53 mutations. Specific aims of the project include: 1) Assess whether clearance of TP53 mutated clones translates into a predictive biomarker of long term benefit from ibrutinib treatment in CLL. 2) Assess whether plasma cell free DNA represents a sensitive tool that can early and dynamically inform on the development of ibrutinib resistant mutations in CLL.