Current Therapeutic Sequencing in Chronic Lymphocytic Leukemia

Area of Science:

• Hematology
• Oncology
• Pharmacology

Background:

• Chronic lymphocytic leukemia (CLL) is the most common adult leukemia with evolving treatment strategies.
• Patient risk stratification is crucial, based on IGHV mutational status, TP53 disruption, and karyotype.
• Current therapeutic approaches are continuously being refined.

Purpose of the Study:

• To provide an overview of current therapeutic algorithms for chronic lymphocytic leukemia (CLL).
• To discuss treatment strategies for both treatment-naïve and relapsed/refractory CLL patients.
• To highlight challenges and advancements in CLL management.

Main Methods:

• Review of current clinical guidelines and published literature on CLL treatment.
• Analysis of efficacy data for targeted therapies including BCL2 inhibitors and BTK inhibitors (BTKi).
• Synthesis of treatment sequencing recommendations for different risk categories and disease states.

Main Results:

• For low- and intermediate-risk, treatment-naïve CLL, venetoclax plus obinutuzumab and second-generation BTKi (acalabrutinib, zanubrutinib) are effective first-line options.
• High-risk CLL patients showed limited benefit from fixed-duration venetoclax therapies; continuous BTKi demonstrated favorable outcomes.
• Established treatment sequences for relapsed/refractory CLL include venetoclax plus rituximab for BTKi-refractory cases and second-generation BTKi for venetoclax-refractory early relapse.

Conclusions:

• The treatment of CLL is dynamic, with distinct strategies for different risk groups and disease phases.
• Managing acquired resistance and optimizing treatment sequencing remain key challenges in CLL therapy.
• Current data support specific therapeutic algorithms for both newly diagnosed and relapsed/refractory CLL.