Navigating the Evolving Treatment Landscape of Relapsed/Refractory Chronic Lymphocytic Leukemia

In this OncLive Insights program, Dr. Mazyar Shadman and Dr. Jennifer J. Huang discuss the evolving treatment landscape for relapsed/refractory chronic lymphocytic leukemia (CLL), focusing on treatment selection, sequencing, and the integration of chimeric antigen receptor (CAR) T-cell therapy. They review how prior treatment exposure, duration of response, and reasons for discontinuation, including disease progression and intolerance, influence subsequent treatment decisions. The discussion explores treatment options following covalent Bruton tyrosine kinase (BTK) inhibitor therapy, including pirtobrutinib and venetoclax-based regimens, as well as the role of resistance mutations and emerging investigational therapies. The experts emphasize timely referral to specialized centers for CAR T-cell evaluation and discuss patient selection, clinical evidence, disease control, and bridging strategies. A clinical scenario illustrates treatment planning following progression on multiple therapies. The program concludes with a discussion of post-CAR T-cell therapy toxicity management, long-term monitoring, coordination between specialized centers and referring clinicians, and the importance of early referral.