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

G Ishdorj; Z Nugent; M Squires; S Kost; V Banerji; L Davidson; C S Katyal; A Marshall; S B Gibson; J B Johnston

doi:10.1016/j.leukres.2021.106628

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

Leuk Res. 2021 Oct:109:106628. doi: 10.1016/j.leukres.2021.106628. Epub 2021 Jun 2.

Authors

G Ishdorj¹, Z Nugent², M Squires¹, S Kost¹, V Banerji³, L Davidson¹, C S Katyal¹, A Marshall⁴, S B Gibson⁵, J B Johnston⁶

Affiliations

¹ CancerCare Manitoba Research Institute (Formerly, Manitoba Institute of Cell Biology), University of Manitoba, Winnipeg, MB, Canada.
² CancerCare Manitoba Research Institute (Formerly, Manitoba Institute of Cell Biology), University of Manitoba, Winnipeg, MB, Canada; Department of Epidemiology and Cancer Registry, Cancer Care Manitoba, Winnipeg, MB, Canada.
³ CancerCare Manitoba Research Institute (Formerly, Manitoba Institute of Cell Biology), University of Manitoba, Winnipeg, MB, Canada; Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada.
⁴ Department of Immunology, University of Manitoba, Winnipeg, MB, Canada.
⁵ CancerCare Manitoba Research Institute (Formerly, Manitoba Institute of Cell Biology), University of Manitoba, Winnipeg, MB, Canada; Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada.
⁶ CancerCare Manitoba Research Institute (Formerly, Manitoba Institute of Cell Biology), University of Manitoba, Winnipeg, MB, Canada; Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada. Electronic address: jjohnsto@cancercare.mb.ca.

PMID: 34134067
DOI: 10.1016/j.leukres.2021.106628

Abstract

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.

Keywords: Chronic lymphocytic leukemia; Cytokines; Exosomes; Ibrutinib; Physical performance; Symptoms.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Activities of Daily Living*
Adenine / analogs & derivatives*
Adenine / therapeutic use
Aged
Cytokines / blood*
Female
Follow-Up Studies
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / blood
Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
Leukemia, Lymphocytic, Chronic, B-Cell / pathology
Male
Pilot Projects
Piperidines / therapeutic use*
Prognosis
Prospective Studies
Symptom Assessment / methods*

Substances

Cytokines
Piperidines
ibrutinib
Adenine