Rapid improvement in symptoms and physical function following ibrutinib initiation in chronic lymphocytic leukemia and the associated changes in plasma cytokines

• Published in: Leukemia research 2021-10, Vol.109, p.106628-106628, Article 106628
• Main Authors: Ishdorj, G., Nugent, Z., Squires, M., Kost, S., Banerji, V., Davidson, L., Katyal, C.S., Marshall, A., Gibson, S.B., Johnston, J.B.
• Format: Article
• Language: English
• Subjects: Chronic lymphocytic leukemia; Cytokines; Exosomes; Ibrutinib; Physical performance; Symptoms
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2021.106628

•Significant improvement in fatigue, shortness of breath and a sense of unwellness occurs within 2 weeks of starting ibrutinib in CLL patients.•Ibrutinib rapidly improves physical activities, such as sit-to-stand and 4 m walking speeds, in CLL patients.•Ibrutinib suppresses the inflammatory cytokine and signaling molecules, TNF-α/-β, CCL3, CCL4, CCL17, and IL-16 levels, in CLL patients. A prospective pilot study was carried out on 34 CLL patients treated with ibrutinib, evaluating the effects on symptoms and physical function with changes in plasma exosomes (EXs), β2-microglobulin (β2M) and 26 plasma cytokines. The revised Edmonton Symptom Assessment Scale (ESAS-R) demonstrated moderate fatigue, shortness of breath and a sense of unwellness before treatment, which significantly improved within 2 weeks of starting ibrutinib. These changes were associated with a rapid improvement in sit-to-stand and 4 m walking speeds. The plasma levels of CCL11, IL-7, -8 and -10 dropped initially while the levels of TNF-α/-β, CCL3, CCL4, CCL17, and IL-16 continued to decline for 12 months. Despite the initial lymphocytosis, plasma β2M levels fell but no consistent change in plasma EXs occurred. Thus, ibrutinib can produce a rapid and sustained improvement in symptoms and physical function in CLL, associated with a decline in multiple plasma cytokines.