The pharmacology of blinatumomab: state of the art on pharmacodynamics, pharmacokinetics, adverse drug reactions and evaluation in clinical trials

Abstract

What is known and objective Bispecific drugs (BDs) belong to the family of immunotherapies along with checkpoint inhibitors and CAR‐T cells. In the field of oncology, BDs are designed to simultaneously bind a tumour antigen on the one side and an antigen present on the surface of effector cells on the other. This review summarizes the information available to date on the first marketed BiTE‐format bispecific antibody, blinatumomab BLINCYTO® in acute lymphoblastic leukaemia. Methods A literature search was conducted in the PubMed database by including studies published in English using the term blinatumomab. Furthermore, bibliographies of selected references were also evaluated for relevant articles. Clinical trial (CT) data were retrieved from clinicaltrials.gov (ongoing trials, adverse events [AEs]) and global pharmacovigilance data were retrieved from VigiBase®. Results and discussion Blinatumomab is a fusion protein which consists of two single‐chain variable fragments arranged in tandem: the first binds the CD19 surface antigen of all B cells and the second targets the CD3 antigen of T cells. Binding of blinatumomab to B and T cells induces apoptosis of B cells after secretion of granzymes and perforins by T cells. T‐cell activation results in secretion of pro‐inflammatory cytokines and upregulation of activation markers and adhesion molecules on the surface of T cells. The major CTs that led to an indication show increased overall survival with blinatumomab with better efficacy in patients in haematological remission with minimal residual disease ≥10−3. The major AEs are cytokine release syndrome, neurotoxicity and hypogammaglobulinemia. The three most frequent system organ classes in CTs are haematological, gastrointestinal and general disorders. These results are also found in VigiBase® but neurological disorders and infections appear more frequently in real life. What is new and conclusion This review summarizes the current knowledge of blinatumomab in the literature. The subject of many CTs is to improve the route of administration and expand the indications for treatment.

A dual-targeting approach using a human bispecific antibody against the receptor-binding domain of the Middle East Respiratory Syndrome Coronavirus

“…This indicates the high thermal stability and potential resilience of K207.C under physiological conditions. Additionally, compared to traditional scFv-based bsAbs, such as blinatumomab, the first FDA-approved scFv-based bsAb with a notably short half-life of approximately 2.1 h, necessitating continuous intravenous infusion for administration, the IgG-based design of K207.C is expected to confer an extended in vivo half-life ( Andersen et al, 2014 ; Mocquot et al, 2022 ). Moreover, the fully human IgG-based format, particularly the IgG4 used in K207.C, reduces the risk of immunogenicity and unwanted in vivo toxicity caused by IgG1-mediated effector functions, such as antibody-dependent cell cytotoxicity ( Harding et al, 2010 ; Schlothauer et al, 2016 ).…”

Blinatumomab as maintenance therapy for pediatric acute B-lymphoblastic leukemia in the setting of asparaginase-associated pancreatitis

“…Of note, the patient continued to receive IT chemotherapy to mitigate risk of CNS relapse, as the CNS activity of blinatumomab is not significant or widely agreed upon. [44][45][46][47][48] As immunotherapeutic and other novel agents demonstrate success, the challenge is to determine the settings in which they will be most effective and the optimal patients to receive them. The role of blinatumomab in upfront pediatric and infant B-ALL therapy is currently being investigated in cooperative group trials, including COG AALL1731 and Interfant-21, respectively.…”

Immunotherapy in Acute Myeloid Leukemia: A Literature Review of Emerging Strategies

“…Antibody-based therapies enclose differently-structured molecules able to bind an effector cell to AML blasts in order to activate the immune response [32]. One successful example of this class of drugs is Blinatumomab, a paradigm-shifting bispecific T-cell engager (BiTE), which has first been shown to prolong survival in acute lymphoblastic leukemia (ALL) [33]. Bispecific antibodies used in cancer immunotherapy have dual affinities targeting both tumor and immune cells, engaging them and promoting effective antitumoral responses.…”