Drs. Fahkri and Seshadri discuss recent studies on novel fixed-duration combinations and MRD-guided regimens for CLL. The Sequoia RMD study showed high efficacy with zanubrutinib and venetoclax, achieving a 99% response rate. Similarly, a phase 1 study with sornotoclax and zanubrutinib showed a 96% response rate. The UK FLAIR study demonstrated superior PFS and overall survival with ibrutinib plus venetoclax. The CLL18 trial evaluates MRD-guided vs. fixed-duration treatments with venetoclax and obinutuzumab or pirtobrutinib. Future CLL therapies may increasingly rely on MRD-guided approaches.