Revelations in CLL biology and advancements in molecular profiling have led to better patient stratification and to the discovery of CLL-specific targets (e.g., BTK, PI3K, BCL-2), prompting CLL’s own targeted small-molecule inhibitor era, led by the Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib, which has demonstrated durable responses in both front-line and relapsed/refractory settings in addition to the treatment of high-risk disease patients (e.g., TP53 alterations) [3,4,5,6]. This evidence concerns the gene TP53 and B-cell chronic lymphocytic leukemia.