Next-Generation Sequencing—Optimal Sequencing of Therapies in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

Purpose of Review This research paper aims to provide an overview of evidence-based sequencing of therapies in relapsed/refractory chronic lymphocytic leukemia (CLL) in the era of targeted drugs. Recent Findings In the absence of data from randomized clinical trials comparing novel agents head-to-head, growing evidence suggests that patients with late relapse (> 2 years) after fixed-duration therapies benefit from identical retreatment, whereas a class switch is favorable in those with short-lived remissions or progressive disease on continuous drug intake. Treatment of patients previously exposed to both covalent inhibitors of BTK and BCL2 remains an unmet medical need. Novel drugs, in particular noncovalent BTKI, show promising efficacy in this difficult-to-treat subgroup in early clinical trials. Summary The optimal sequencing of therapies in CLL requires consideration of individual patient factors and disease characteristics. Double-refractory disease continuous to pose a clinical challenge with a focus on participation in clinical trials whenever possible.