Characterizing the kinetics of lymphocytosis in patients with chronic lymphocytic leukemia treated with single-agent ibrutinib

• Published in: Leukemia & lymphoma 2019-03, Vol.60 (4), p.1000-1005
• Main Authors: Barrientos, Jacqueline C., Burger, Jan A., Byrd, John C., Hillmen, Peter, Zhou, Cathy, Ninomoto, Joi, James, Danelle F., Kipps, Thomas J.
• Format: Article
• Language: English
• Subjects: Adenine - analogs & derivatives; Agammaglobulinaemia Tyrosine Kinase - antagonists & inhibitors; Biomarkers; Bruton's tyrosine kinase inhibitor; chronic lymphocytic leukemia; Follow-Up Studies; Humans; Ibrutinib; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - mortality; lymphocytosis; Lymphocytosis - pathology; Molecular Targeted Therapy; Piperidines; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyrazoles - administration & dosage; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; small lymphocytic lymphoma; Treatment Outcome
• ISSN: 1042-8194; 1029-2403
• DOI: 10.1080/10428194.2018.1512710

Increased absolute lymphocyte count (ALC) is a key feature of chronic lymphocytic leukemia (CLL) but is also observed during treatment with B-cell receptor pathway inhibitors including ibrutinib, a first-in-class inhibitor of Bruton's tyrosine kinase. In patients with CLL treated with single-agent ibrutinib in two multicenter, open-label, randomized, phase 3 studies (RESONATE-2, NCT01722487; RESONATE, NCT01578707), lymphocytosis was observed in 77 of 136 (57%) patients treated in first-line and 133 of 195 (69%) relapsed/refractory patients. On treatment, lymphocytosis resolved in 95% of patients in the first-line and 94% in the relapsed/refractory setting. The median duration of lymphocytosis was 12 and 14 weeks in the first-line and relapsed/refractory settings, respectively. Lymphocytosis is a common and predictable pharmacodynamic effect of ibrutinib treatment, and in the absence of other signs of progression, does not represent disease progression. Lymphocytosis resolves in the majority of patients and does not require interruption or discontinuation of ibrutinib therapy.