S7 Ep14: Choosing Wisely in CLL: A Deep Dive Into Frontline Treatment

In this episode of Treating Together, host Marc Braunstein, MD, PhD, associate professor of medicine at the NYU Perlmutter Cancer Center, sits down with Adam Kittai, MD, associate professor and director of the CLL and Lymphoma programs at NYU Perlmutter Cancer Center, for a deep dive into the rapidly evolving frontline treatment landscape in chronic lymphocytic leukemia (CLL). As chemotherapy continues to give way to targeted and time-limited therapies, clinicians face an increasingly complex array of choices, each influenced by disease biology, patient preferences, and emerging clinical trial data. Key Discussion PointsThe episode focuses on the evolving frontline management of CLL and how clinicians can individualize therapy in an era of expanding options. Highlights include: Patient Evaluation and Diagnosis Considerations: Beyond traditional risk factors such as TP53 mutation and IGHV status, importance is also being placed on patient preference, comorbidities, and treatment goals (eg, time-limited vs continuous therapy) to guide treatment decisions. Therapy Selection and Sequencing Strategy: Dr Kittai offers his view on sequencing decisions in the front line: given the lack of robust comparative data, current evidence supports prioritizing the most appropriate upfront regimen rather than relying on uncertain sequencing strategies across agents. Insights From the AMPLIFY Trial (NCT03836261): With the recent February 2026 FDA approval of acalabrutinib (Calquence) plus venetoclax (Venclexta) in the front line, the discussion highlights progression-free survival (PFS) benefits seen in the AMPLIFY trial and favorable safety of the doublet. The Growing Role of Minimal Residual Disease (MRD): The discussion briefly pivots to the use of MRD testing in the clinic today, including data from trials like GLOW (NCT03462719) and FLAIR (EudraCT: 2013-001944-76), and its potential to guide treatment duration. Emerging Therapeutic Strategies in the Pipeline: The conversation looks to the future of CLL care, including Bruton tyrosine kinase (BTK) degraders, next-generation BCL-2 inhibitors, and novel combinations currently under investigation. Managing Richter’s Transformation: Dr Kittai covers evolving combination approaches for this aggressive cancer that aim to target both CLL and lymphoma biology, moving beyond chemoimmunotherapy.