Intolerance is the most common reason for discontinuing PI3K or BTK inhibitor drugs used for the treatment of chronic lymphocytic leukemia (CLL), and it has been found that the intolerant patient population may benefit from an alternative drug if adverse effects arise. Here, Anthony Mato, MD, MSCE, from Memorial Sloan Kettering Cancer Center, New York, NY, discusses the use of umbralisib in patients who are intolerant to ibrutinib, acalabrutinib or idelalisib, aiming to lower toxicity in patients whilst still achieving high response rates. This interview was recorded at the American Society of Oncology (ASCO) 2018 Annual Meeting, held in Chicago, IL.