Initial management of chronic lymphocytic leukemia

BTK: Bruton tyrosine kinase; IGHV: immunoglobulin heavy chain variable region.

* Lymphocytosis itself, even if extreme, is not a strict indication for treatment. Likewise, treatment is not indicated solely on the basis of hypogammaglobulinemia or the presence of a monoclonal or oligoclonal paraproteinemia.

¶ Treatment is indicated if the patient develops significant disease-related complications at any time. During observation, we perform blood counts at 3-month intervals along with a clinical examination. At the end of 12 months, these evaluations can determine disease aggressiveness. The interval of examination may be lengthened for those with clinically stable disease.

Δ The choice among targeted agents is strongly dependent upon patient comorbidities and preferences. Fixed-duration therapy is more intensive and logistically complicated but offers a treatment-free interval. Continuous therapy is given until progression or unacceptable toxicity. When selecting among the BTK inhibitors, we prefer acalabrutinib or zanubrutinib rather than ibrutinib as they appear to be at least as effective and better tolerated than ibrutinib. These two agents have not been compared directly. However, in our practice, if the goal is best efficacy with acceptable tolerability, we offer zanubrutinib. If the goal is best tolerability with good efficacy, we offer acalabrutinib. The addition of obinutuzumab to acalabrutinib increases efficacy and increases toxicity with higher rates of cytopenias and infections. Ibrutinib plus obinutuzumab has not been directly compared versus ibrutinib. Further details on the impact of comorbidities and drug interactions are provided in related UpToDate content.

◊ In patients with del17p or TP53 mutation, continuous acalabrutinib or zanubrutinib may be preferred over fixed-duration venetoclax plus obinutuzumab based on cross-trial comparisons that suggest decreased efficacy of the latter in this population.