Chronic Lymphocytic Leukaemia: Management

Key points

• Not all CLL needs treatment — asymptomatic early-stage disease is monitored ('watch and wait'). The iwCLL indications below define when to treat.
• Progressive marrow failure: developing or worsening anaemia and/or thrombocytopenia.
• Massive (over 10 cm) or progressive lymphadenopathy; massive (over 6 cm) or progressive splenomegaly.
• Progressive lymphocytosis: over 50% increase in 2 months, or a lymphocyte doubling time under 6 months; also autoimmune cytopenias not responding to steroids, or marked symptoms.
• When treatment is indicated, first-line is now targeted therapy: a BTK inhibitor (ibrutinib, acalabrutinib, zanubrutinib) or venetoclax (BCL-2 inhibitor) + obinutuzumab; chemoimmunotherapy (e.g. FCR) is now rarely used. Check TP53 mutation / del(17p), which predicts poor response to chemoimmunotherapy and favours targeted agents.