Abstract / Summary
Abstract: The treatment landscape for chronic lymphocytic leukemia (CLL) has rapidly evolved from chemoimmunotherapy to highly effective targeted agents. Despite superior efficacy and safety profiles of these novel agents, challenges persist, particularly due to limited head-to-head trials and regional differences in drug availability and molecular testing. This multiregional expert consensus, developed by 13 hematology experts from Latin America, the Middle East and Africa, Asia Pacific, and Russia, using an adapted Delphi approach, provides evidence-informed recommendations for first-line treatment and sequencing tailored to patient risk and real-world resource constraints. The panel agreed on 16 key statements, emphasizing that targeted therapies are preferred for nearly all newly diagnosed patients. Molecular testing for deletion of the short arm of chromosome 17 (del[17p]), tumor protein 53 ( TP53 ) mutation, and immunoglobulin heavy-chain variable region ( IGHV ) status is recommended for prognosis and treatment planning. Patients at high risk (del[17p] and/or TP53 mutation) should preferably receive continuous therapy with second-generation Bruton’s tyrosine kinase inhibitors (BTKis; acalabrutinib or zanubrutinib), which are generally preferred over ibrutinib due to safety advantages. Patients at low risk ( IGHV mutation, without del[17p]/ TP53 ) are best suited for time-limited, venetoclax-based regimens. On relapse, switching therapeutic classes is recommended: venetoclax after continuous BTKi therapy, and BTKis after fixed-duration venetoclax. Overall, the consensus underscores the importance of individualized, shared decision-making that accounts for molecular risk, comorbidities, and patient preferences, while highlighting global disparities in access to modern CLL therapies.