In this video, Dr. Talha Munir, a hematology consultant at St. James’s Hospital in Leeds, UK, discusses the treatment options for a 76-year-old gentleman with Binet stage C and Rai stage 3 CLL with unmutated IGHV status and ATM gene deletion. Chemoimmunotherapy is excluded due to the patient’s condition, and the chosen treatment is venetoclax with obinutuzumab as fixed-duration therapy for 12 months. Continuous BTK-inhibitor therapy may also be an option, but the patient preferred fixed-duration therapy. The patient’s history of ischemic heart disease and need for antiplatelet therapy were also considered, with aspirin use indicating acalabrutinib or ibrutinib may be reasonable. Fixed-duration ibrutinib with venetoclax is also an option, though not yet licensed, and targeted drugs can mitigate the negative impact of ATM gene deletion.