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Jeremy S. Abramson, MD, MMSc
Jeremy S. Abramson, MD, MMSc
Posted: Monday, March 24, 2025
Distinct variations in lymphocytosis patterns may emerge, dependent upon treatment with select covalent Bruton’s tyrosine kinase (BTK) inhibitors, in patients with chronic lymphocytic leukemia (CLL), according to a study conducted by Luca Laurenti, MD, of the Catholic University of the Sacred Heart, Rome, and colleagues. In fact, first-line treatment with the covalent BTK inhibitors ibrutinib vs acalabrutinib led to temporal-dependent differences in peripheral blood lymphocytosis for this patient population. The findings of this retrospective study across 17 Italian centers were published in HemaSphere.
“We observed that while there is an appreciable reduction in lymphocyte count starting from the second month of treatment in both groups, the decrease in lymphocytosis appears to be faster and more profound in patients treated with acalabrutinib from the sixth month onward,” stated the investigators. “This observation confirms previous works identifying lymphocytosis as a ‘class effect’ of covalent BTK inhibitors.”
Patients with CLL (n = 204) who had received either ibrutinib (n = 136) or acalabrutinib (n = 68) as first-line therapy were included in the study analyses. Clinical and molecular features were assessed at baseline, and absolute lymphocyte count was measured at 2 weeks and every 3 months thereafter for 12 months. To evaluate their molecular impact on lymphocytosis, IGHV mutational status, TP53 mutations, and chromosomal abnormalities were analyzed.
Acalabrutinib led to a more rapid and pronounced decline in lymphocyte counts, particularly after the sixth month. Molecular analyses indicated that patients with IGHV mutations who received acalabrutinib exhibited a steeper decline in lymphocyte counts compared with the ibrutinib group. TP53 mutations and NOTCH1 mutations did not seem to significantly impact the overall kinetics of lymphocytosis. By month 12, acalabrutinib-treated patients reached normal lymphocyte levels, whereas the ibrutinib group retained elevated lymphocyte counts.
“The main differences of lymphocytes count between the two covalent BTK inhibitors is due to IGHV-mutated status,” proposed the study authors.
Disclosure: Dr. Laurenti reported no conflicts of interest. For full disclosures of the other study authors, visit onlinelibrary.wiley.org.
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