Redefining CLL Management: BTK Inhibitors, BCL-2 Targeting, and MRD-Driven Strategies

The management of chronic lymphocytic leukemia (CLL) is undergoing a profound transformation. Targeted therapies - most notably Bruton’s tyrosine kinase inhibitors (BTKi) and BCL-2 antagonists - have fundamentally altered the treatment landscape, delivering meaningful improvements across disease settings and in patients carrying high-risk molecular features. Fixed-duration and combination regimens are reshaping longstanding treatment paradigms, while the emergence of non-covalent BTKi and novel combinatorial approaches is broadening therapeutic options and beginning to address the mechanisms underlying acquired resistance.In parallel, measurable residual disease (MRD) assessment has risen to prominence as a critical tool in CLL - informing response evaluation, prognostication, and increasingly, treatment decisions at the individual patient level. Highly sensitive MRD detection platforms are now enabling adaptive, MRD-guided strategies that seek to optimize efficacy while reducing cumulative toxicity and unnecessary treatment exposure.Despite these remarkable advances, key challenges remain. Resistance to covalent BTKi, the optimal sequencing of targeted agents, and the clinical implementation of MRD monitoring in routine practice are all areas of active investigation. Questions around biomarker-driven treatment individualization, the role of emerging immunotherapeutic modalities, and the translation of trial findings to real-world populations continue to define the frontier of CLL research.This Research Topic aims to bring together the latest clinical and translational advances shaping precision medicine in CLL. We welcome contributions across all article types - including original research, systematic reviews, meta-analyses, perspectives, and case reports - addressing, but not limited to:o BTKi therapy: covalent and non-covalent agents, resistance mechanisms, and clinical outcomeso Venetoclax-based combinations and fixed-duration treatment strategieso MRD assessment methods, clinical utility, and MRD-guided treatment adaptationo Biomarker discovery and prognostic stratification in CLLo Sequencing and re-treatment strategies in relapsed/refractory diseaseo Emerging immunotherapeutic approaches and novel agents in developmentWe invite researchers, clinicians, and translational scientists to contribute to this collection and join a growing international conversation around the evolving standard of care in CLL. Topic editors: Stefano Molica, Narendranath Epperla, Vanessa Innao Source: https://www.frontiersin.org/research-topics/81870/redefining-cll-management-btk-inhibitors-bcl-2-targeting-and-mrd-driven-strategies