Blinatumomab differentially modulates peripheral blood and bone marrow immune cell repertoire: A Campus ALL study

Summary Blinatumomab is the first bi‐specific T‐cell engager approved for relapsed or refractory B‐cell precursor acute lymphoblastic leukaemia (B‐ALL). Despite remarkable clinical results, the effects of blinatumomab on the host immune cell repertoire are not fully elucidated. In the present study,...

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Published in:British journal of haematology 2023-11, Vol.203 (4), p.637-650
Main Authors: Ocadlikova, Darina, Lussana, Federico, Fracchiolla, Nicola, Bonifacio, Massimiliano, Santoro, Lidia, Delia, Mario, Chiaretti, Sabina, Pasciolla, Crescenza, Cignetti, Alessandro, Forghieri, Fabio, Grimaldi, Francesco, Corradi, Giulia, Zannoni, Letizia, De Propris, Stefania, Borleri, Gian Maria, Tanasi, Ilaria, Vadakekolathu, Jayakumar, Rutella, Sergio, Guarini, Anna Rita, Foà, Robin, Curti, Antonio
Format: Article
Language:English
Subjects:
acute lymphoblastic leukaemia
Acute lymphoblastic leukemia
blinatumomab
Bone marrow
CD4 antigen
CD8 antigen
Cytotoxicity
Flow cytometry
Hematology
immune cells
Immune checkpoint
immune checkpoint receptors
Lymphocytes T
Peripheral blood
Phenotypes
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Summary:Summary Blinatumomab is the first bi‐specific T‐cell engager approved for relapsed or refractory B‐cell precursor acute lymphoblastic leukaemia (B‐ALL). Despite remarkable clinical results, the effects of blinatumomab on the host immune cell repertoire are not fully elucidated. In the present study, we characterized the peripheral blood (PB) and, for the first time, the bone marrow (BM) immune cell repertoire upon blinatumomab treatment. Twenty‐nine patients with B‐ALL received blinatumomab according to clinical practice. Deep multiparametric flow cytometry was used to characterize lymphoid subsets during the first treatment cycle. Blinatumomab induced a transient redistribution of PB effector T‐cell subsets and Treg cells with a persistent increase in cytotoxic NK cells, which was associated with a transient upregulation of immune checkpoint receptors on PB CD4 and CD8 T‐cell subpopulations and of CD39 expression on suppressive Treg cells. Of note, BM immune T‐cell subsets showed a broader post‐treatment subversion, including the modulation of markers associated with a T‐cell‐exhausted phenotype. In conclusion, our study indicates that blinatumomab differentially modulates the PB and BM immune cell repertoire, which may have relevant clinical implications in the therapeutic setting.
ISSN:0007-1048
1365-2141
DOI:10.1111/bjh.19104