ASH 2021 | Updates in CLL: key clinical trials in the frontline and R/R setting, pre-clinical data and MRD

Jennifer Woyach, MD and Adam Kittai, MD, Ohio State University College of Medicine, Columbus, OH, share some of the most exciting updates in chronic lymphocytic leukemia (CLL) presented at the ASH 2021 annual meeting. To begin with, Dr Woyach and Dr Kittai comment on the positive results of the CAPTIVATE (NCT02910583), GLOW (NCT03462719) and CLL13 (NCT02950051) clinical trials evaluating ibrutinib-venetoclax-based regimens in the frontline treatment of patients with CLL. Dr Woyach and Dr Kittai then discuss the place of the ibrutinib-venetoclax combination in the context of existing treatments in the treatment-naïve setting, and then move on to the long-term follow-up data of the ALLIANCE A041202 (NCT01886872) and SEQUOIA (NCT03336333) studies comparing ibrutinib-based treatment regimens to chemoimmunotherapy, and zanubrutinib to bendamustine and rituximab respectively in patients with previously untreated CLL. Moving forward, Dr Woyach and Dr Kittai discuss the mechanism of action and share short-term data on pirtobrutinib and MK-1026, two reversible Bruton’s tyrosine kinase inhibitors (BTKi) currently being investigated in the relapsed/refractory (R/R) setting. They explain that both agents appear to have excellent efficacy but have different safety profiles due to their contrasting selectivity. Further data is needed to determine their long-term efficacy as well as potential mechanisms of resistance to these drugs. Subsequently, Dr Woyach and Dr Kittai outline some promising molecules in pre-clinical studies for CLL, namely the CDK9 inhibitor VIP152 and the Bcl-2/Bcl-xL inhibitor LP-118. Finally, Dr Woyach and Dr Kittai talk on the increasingly important role of measurable residual disease (MRD) as a clinical endpoint in CLL and outline some of the remaining questions on this topic. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.