In relapsed chronic lymphocytic leukemia (CLL), the choice of therapy depends on the risk profile, prior therapy, and patient comorbidities. The first novel agent for patients who had previously received chemoimmunotherapy is typically a BTK inhibitor or combination venetoclax + rituximab. For patients with problematic comorbidities, however, a PI3K inhibitor can be used, but generally this is reserved for later lines of therapy. For those who stop ibrutinib due to adverse events, there are broad options but data are still limited. For those whose disease progresses on a BTK inhibitor, the only prospective data are for use of venetoclax. For patients who have been treated with venetoclax + rituximab and experience relapse, retreatment is a possibility if they have had a durable remission. Finally, undetectable minimal residual disease is strongly predictive of durability of response for time-limited regimens but not for continuous BTK inhibition, and is generally not indicated for monitoring patients.
Disclosures: Dr. Brown has disclosed receiving consulting fees from AbbVie, Inc., Acerta Pharmaceuticals LP, AstraZeneca Pharmaceuticals LP, BeiGene, Catapult Therapeutics, Eli Lilly and Company, Genentech, Inc., Juno Therapeutics, Inc./Celgene Corporation, MEI Pharma Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., and Rigel Pharmaceuticals, Inc.; receiving grant/research support from Loxo Oncology, Inc., TG Therapeutics, and Verastem, Inc.; and receiving other financial benefit from MorphoSys AG.