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

Abstract

SummaryBlinatumomab 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.

Efficacy of blinatumomab as maintenance therapy for B-lineage acute lymphoblastic leukemia/lymphoma following allogeneic hematopoietic cell transplantation

“…A phase Ib/II trial that enrolled high-risk CD19-positive B-ALL and non-Hodgkin lymphoma patients who had attained MRD-negative CR after allo-HSCT recorded a 3-year RFS of 73% [ 14 ]. In the Campus ALL study, blinatumomab led to a transient redistribution of effector T-cell subsets and Treg cells, along with a persistent increase in cytotoxic NK cells in the peripheral blood [ 15 ].…”