Reconstitution of humoral immunity and decreased risk of infections in patients with chronic lymphocytic leukemia treated with Bruton tyrosine kinase inhibitors

Abstract

Immune dysregulation in chronic lymphocytic leukemia (CLL) contributes to a high rate of infections and morbidity. The Bruton tyrosine kinase (BTK) inhibitors ibrutinib and acalabrutinib mark major breakthroughs in the treatment of CLL, however many patients require long-term therapy with these agents. Despite receiving effective therapy for CLL, patients on BTK inhibitors remain immunocompromised and at risk of infectious complications. We previously reported that treatment of CLL with ibrutinib leads to partial reconstitution of humoral immunity and fewer infections during the first two years of therapy. It is currently unclear whether the positive effects of ibrutinib on the immune system are sustained during long-term therapy. Acalabrutinib is a newer, more selective BTK inhibitor than ibrutinib; however a detailed evaluation of the immunologic impact of acalabrutinib therapy is lacking. Herein, utilizing two independent trials, we assessed the immunological effects and infectious risk of ibrutinib and acalabrutinib treatment in patients with CLL.

Keywords:

• CLL
• BTK inhibitor
• ibrutinib
• acalabrutinib
• infection
• immune system

Acknowledgements

The authors thank our patients for participating in these studies, Pharmacyclics LLC, an AbbVie Company, and Acerta for providing ibrutinib and acalabrutinib respectively, research support, and comments on the manuscript.

Disclosure statement

Adrian Wiestner received research support from Pharmacyclics LLC, an Abbvie company and Acerta Pharma, a member of the Astra-Zeneca group, Merck, Nurix, and Genmab. Inhye Ahn received research support from the American Society of Hematology Scholar Award. The remaining authors report no conflicts of interest.

Additional information

Funding

The authors are supported by the Intramural Research Program of the NHLBI, NIH. Pharmacyclics LLC, an Abbvie company and Acerta Pharma, a member of the Astra-Zeneca group provided study drug and research support.