Over recent years, the first-line therapeutic approach explored in CLL clinical trials has followed two main roads: continuous anti-BTK inhibitors, (BTKi)-based therapy, whose efficacy is independent from the achievement of uMRD [49,50], and fixed-duration schemas with uMRD as a relevant end-point of efficacy based on venetoclax and anti-CD20 monoclonal antibodies [41,42,43] or on venetoclax and ibrutinib, associated with progressively higher rates of MRD negativity [12,44,46]. The gene discussed is BTK; the disease is B-cell chronic lymphocytic leukemia.