Thomas Kipps, MD, PhD, UC San Diego, Moores Cancer Center, La Jolla, CA, discusses data from clinical trials that have tested combinations of different types of agents, such as venetoclax and rituximab, which showed high remission, or venetoclax plus anti-CD20 agent obinutuzumab, where a high proportion of patients achieved eradication of detectable minimal residual disease (MRD). The combination of a Bruton’s tyrosine kinase (BTK) inhibitor with a B-cell lymphoma 2 (Bcl-2) inhibitor, with or without an anti-CD20 agent, is undergoing. Still, preliminary data cannot clear MRD in a sizable proportion of patients. Overall, the inhibition of the Bcl-2 proteins must consider their role in survival in normal cells to avoid toxicity. New avenues include targeting embryonic proteins that are only expressed in adult cancer cells. Future developments should investigate the mechanisms of survival of leukemic cells and their interactions with their microenvironment. This interview took place at the Lymphoma, Leukemia & Myeloma Congress 2021.