Key clinical point: Newly identified gene mutations in the progression of venetoclax-treated relapsed chronic lymphocytic leukemia (CLL) may enhance understanding of clinical resistance mechanisms underlying the disease.

Major finding: During venetoclax treatment, several novel BCL2 resistance mutations were acquired in conjunction with already present subclonal BCL2 Gly101Val mutations.

Study details: A cohort study of 67 patients with progressive CLL treated with venetoclax.

Disclosures: The study was funded by the Snowdome Foundation, Vision Super and the Wilson Centre for Lymphoma Genomics, the Leukemia and Lymphoma Society, the National Health and Medical Research Council of Australia, and other grant funding sources provided to the study authors. The authors reported financial affiliations with AbbVie, Genentech, and the Walter and Eliza Hall Institute.