Within the last few decades, numerous advances in the treatment of CLL have been made, including the introduction of novel classes of targeted small molecules such as BCL2 inhibitors, BTK inhibitors, or PI3K inhibitors. Randomized clinical trials have demonstrated improved progression free survival with these therapeutics over chemoimmunotherapy in both the first-line and relapsed/refractory setting. These chemotherapy-free regimens have especially helped to improved outcomes in high-risk subgroups, albeit still with reduced activity relative to patients without these high-risk characteristics.11
CLL is a chronic disease; therefore, most patients will relapse on or after treatment with these drugs and will require multiple lines of therapy, especially high-risk subgroups. The major treatment challenge has now shifted from having few therapeutic choices to how best to sequence and combine available agents as well as determine if treat to progression or time-limited treatment might be better.11,12