Richard Rosenquist, MD, PhD, Karolinska Institute, Stockholm, Sweden, discusses mechanisms of resistance and predicting resistance in patients. Patients with chronic lymphocytic leukemia (CLL) can develop resistance to Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib via mutations in the BTK gene or in the downstream PLCG2 gene. Resistance to venetoclax, a BCL-2 inhibitor can additionally occur via mutations in the BCL2 gene. Patients who progress after receiving targeted therapies such as BTK or BCL-2 inhibitors can subsequently be analyzed for mutations in the BTK and PLCG2 genes or BCL2 gene respectively. This interview took place during the 2021 International Conference on Malignant Lymphoma (16-ICML).