Dynamic changes of the normal B lymphocyte repertoire in CLL in response to ibrutinib or FCR chemo-immunotherapy. (3rd April 2018)

• Record Type: Journal Article
• Authors: Schliffke, Simon; Sivina, Mariela; Kim, Ekaterina; von Wenserski, Lisa; Thiele, Benjamin; Akyüz, Nuray; Falker-Gieske, Clemens; Statovci, Donjete; Oberle, Anna; Thenhausen, Toni; Krohn-Grimberghe, Artus; Bokemeyer, Carsten; Jain, Nitin; Estrov, Zeev; Ferrajoli, Alessandra; Wierda, William; Keating, Michael; Burger, Jan A.; Binder, Mascha
• Is Part Of: Oncoimmunology. Volume 7:Number 4(2018)
• Publication Date: 2018-04-03
• Subjects: Ibrutinib -- chronic lymphocytic leukemia -- B lymphocyte repertoire -- chemo-immunotherapy -- Immunomonitoring; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2017.1417720
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Using next-generation immunoglobulin ( IGH ) sequencing and flow cytometry, we characterized the composition, diversity and dynamics of non-malignant B cells in patients undergoing treatment with the Bruton tyrosine kinase (BTK) inhibitor ibrutinib or chemo-immunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR). During ibrutinib therapy, non-malignant B cell numbers declined, but patients maintained stable IGH diversity and constant fractions of IGH -mutated B cells. This indicates partial preservation of antigen-experienced B cells during ibrutinib therapy, but impaired replenishment of the normal B cell pool with naïve B cells. In contrast, after FCR we noted a recovery of normal B cells with a marked predominance of B cells with unmutated IGH . This pattern is compatible with a deletion of pre-existing antigen-experienced B cells followed by repertoire renewal with antigen-naïve B cells. These opposite patterns in B cell dynamics may result in different responses towards neoantigens versus recall antigens, which need to be further defined.