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

Christopher Pleyer; Clare Sun; Sanjal Desai; Inhye E. Ahn; Xin Tian; Pia Nierman; Susan Soto; Jeanine Superata; Janet Valdez; Jennifer Lotter; Adrian Wiestner

doi:10.1080/10428194.2020.1772477

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

Christopher Pleyer, Clare Sun, Sanjal Desai, Inhye E. Ahn, Xin Tian, Pia Nierman, Susan Soto, Jeanine Superata, Janet Valdez, Jennifer Lotter, Adrian Wiestner

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2375-2382
Number of pages	8
Journal	Leukemia and Lymphoma
Volume	61
Issue number	10
DOIs	https://doi.org/10.1080/10428194.2020.1772477
State	Published - Aug 23 2020
Externally published	Yes

Bibliographical note

Funding Information:
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. 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.

Funding Information:
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.

Publisher Copyright:
©, This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.

Keywords

BTK inhibitor
CLL
acalabrutinib
ibrutinib
immune system
infection

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/10428194.2020.1772477

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Pleyer, C., Sun, C., Desai, S., Ahn, I. E., Tian, X., Nierman, P., Soto, S., Superata, J., Valdez, J., Lotter, J., & Wiestner, A. (2020). Reconstitution of humoral immunity and decreased risk of infections in patients with chronic lymphocytic leukemia treated with Bruton tyrosine kinase inhibitors. Leukemia and Lymphoma, 61(10), 2375-2382. https://doi.org/10.1080/10428194.2020.1772477

Pleyer, C, Sun, C, Desai, S, Ahn, IE, Tian, X, Nierman, P, Soto, S, Superata, J, Valdez, J, Lotter, J & Wiestner, A 2020, 'Reconstitution of humoral immunity and decreased risk of infections in patients with chronic lymphocytic leukemia treated with Bruton tyrosine kinase inhibitors', Leukemia and Lymphoma, vol. 61, no. 10, pp. 2375-2382. https://doi.org/10.1080/10428194.2020.1772477

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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.",

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note = "Funding Information: 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. 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. Funding Information: 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. Publisher Copyright: {\textcopyright}, This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.",

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AU - Tian, Xin

AU - Nierman, Pia

AU - Soto, Susan

AU - Superata, Jeanine

AU - Valdez, Janet

AU - Lotter, Jennifer

AU - Wiestner, Adrian

N1 - Funding Information: 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. 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. Funding Information: 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. Publisher Copyright: ©, This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 U.S.C. 105, no copyright protection is available for such works under U.S. Law.

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N2 - 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.

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

Abstract

Bibliographical note

Keywords

UN SDGs

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