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

• Published in: British journal of haematology Vol. 203; no. 4; pp. 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: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01-11-2023
• 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
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/bjh.19104

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.