Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in adults, with an estimated 18,740 new cases in 2023 in the United States and about 40,000 deaths worldwide per year.

A 57-year-old woman diagnosed with CLL in 2020, Binet A, presented cervical lymphadenopathy without cytopenias. Referred to HSPE in July 2023 due to night sweats, weight loss, and progressive lymph node enlargement. Physical examination revealed a conglomerate in bilateral cervical region, occipital, retro and preauricular lymphadenopathy, submandibular, and supraclavicular lymph nodes. Complete blood count: Hemoglobin 8.8 g/dL, leukocytes 130,000/mm3 (lymphocytes 127,850/mm3) and platelets 77,000/mm3. Peripheral blood immunophenotyping: CD5, CD19, CD20, CD23, and CD200 positivity; FISH revealed chromosome 13 deletion, unmutated IGHV and TP53. Hospitalized because of the risk of upper airway obstruction due to lymph nodes enlargement near to the rhino and oropharynx and to initiate ibrutinib therapy. The patient achieved rapid response, with significant lymphadenopathy reduction within 6 days of treatment and complete symptoms improvement. As an expected effect, lymphocytosis of 230,000/mm3 was observed.

Regarding treatment, which until recently was limited to immunochemotherapy, there has been a significant change in the course of the disease since the introduction of oral Bruton's tyrosine kinase (BTK) inhibitors, offering greater safety, efficacy, and improved survival. Ibrutinib, a BTK inhibitor developed in 2009, has become a cornerstone of treatment for high-risk patients and is often recommended as a first-line therapy. BTK molecules regulate the migration and motility of B lymphocytes, and their inhibition results in impaired signaling through BCR, CXCR4, and integrins (responsible for pathway activation, cell growth, and reduced cell death). Inhibition of CXCR4 and integrins leads to loss of cellular adhesion to stromal cells and the extracellular matrix, causing in situ cell death (anoikis), resulting in a process called “redistribution lymphocytosis”, in which a fraction of these cells migrates from lymphoid to bloodstream. Overall response rates typically exceed 80% in first-line therapy for naive-patients. Clinical evolution after starting Ibrutinib showed rapid reduction of lymph node mass in the initial days of medication use. A study demonstrated that lymph node burden significantly decreases after three cycles, with approximately 50% reduction in mass (this report showed significant reduction after 6 days). The choice of BTK inhibitor should be individualized, taking into account medication availability and patient comorbidities. Ibrutinib is generally not myelosuppressive; however, some adverse effects may be observed, such as tumor lysis syndrome, cardiotoxicity, and opportunistic infections.

BTK inhibitors are one of the options for CLL treatment; however, therapy choice should be individualized. Furthermore, potential long-term adverse effects of this drug require monitoring. In future, new combinations of BTK inhibitors with other targeted drugs may expand its role and reduce drug resistance.