Selection of second-line therapy for chronic lymphocytic leukemia

This algorithm presents our general approach to the selection of second-line therapy for CLL. When choosing between multiple acceptable treatment options, we consider patient characteristics as shown in the inset. Selection of third-line therapy is based on prior treatments received and response to these treatments. Patients who discontinue a therapy due to intolerance may be candidates for treatment with a different agent from the same class as long as mechanism of action interfering mutations are not present. BTK inhibitors and venetoclax-based treatment are used prior to other agents. We reserve PI3K inhibitors for patients with relapsed/refractory CLL with prior exposure to both BTK inhibitors and venetoclax.