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Review
. 2020 Feb 14:14:23-34.
doi: 10.2147/BTT.S202746. eCollection 2020.

Blinatumomab for the Treatment of Adult B-Cell Acute Lymphoblastic Leukemia: Toward a New Era of Targeted Immunotherapy

Miguel J Franquiz  1   2 , Nicholas J Short  2
Affiliations
Review

Blinatumomab for the Treatment of Adult B-Cell Acute Lymphoblastic Leukemia: Toward a New Era of Targeted Immunotherapy

Miguel J Franquiz et al. Biologics. .

Abstract

Several therapeutic advancements in the treatment of B-cell acute lymphoblastic leukemia (ALL) have surfaced in the past decade, primarily driven by an increased understanding of the immunopathobiology of this disease. The clinical use of blinatumomab, a bispecific antibody that coordinates cytotoxic CD3+ T lymphocytes and CD19+ lymphoblasts, has resulted in improved outcomes in both relapsed/refractory and minimal residual disease-positive B-cell ALL. Promising emerging data also demonstrate the efficacy of this agent in the frontline setting and in combination regimens. Uncertainty remains regarding the optimal sequencing and combination of blinatumomab with cytotoxic chemotherapy and other emerging agents. The pharmacology and clinical data on blinatumomab for adult B-cell ALL, both as monotherapy and in combinations, will be reviewed herein.

Keywords: B-cell leukemia; acute lymphoblastic leukemia; adult; bispecific antibodies; blinatumomab; precursor cell lymphoblastic leukemia-lymphoma.

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Conflict of interest statement

NJS reports consulting fees from Takeda Oncology and AstraZeneca, research funding from Takeda Oncology and Astellas Pharma Inc., and honoraria from Amgen. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Blinatumomab structure. Variable regions of anti-CD19 and anti-CD3 joined by a serine-glycine linker are recombinantly expressed in Chinese hamster ovary cells.
Figure 2
Figure 2
Blinatumomab mechanism of action. Redirected lysis of CD19 bearing B-cells is achieved through the formation of a cytolytic synapse, first binding malignant B-cells (binding constant for CD19: 10−9 M), followed by coordination of circulating cytotoxic T lymphocytes (binding constant for CD3: 10–7 M). Following binding of CD3, cellular signaling events lead to the production and release of cytotoxic granules containing granzyme and perforin. Perforin forms a pore in the target cell membrane and delivers granzymes into the cytosol, granzymes then activate caspases and induce apoptosis.
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