The BTK inhibitor ibrutinib as single agent allows a long-term disease control that improves over time with its continuous administration in the majority of patients, even in those with TP53 deletion/mutation, and confers an advantage in PSF and OS over ofatumumab in R/R CLL patients and over Chl in elderly TN (104–109), despite the achievement of a clinical CR only in a minority of cases. This evidence concerns the gene TP53 and B-cell chronic lymphocytic leukemia.