Blinatumomab

Blinatumomab is a bispecific antibody construct (see BiTE antibody below) that bridges T cells with malignant B cells in patients with acute lymphoblastic leukemia and activates their destruction.

Blinatumomab is a bispecific T-cell enhancing molecule that binds specifically to CD19 expressed on the surface of B-lineage cells and to CD3 expressed on the surface of T cells. It activates endogenous T cells by linking CD3 in the T cell receptor(TCR) complex with CD19 on benign and malignant B cells. The antitumor activity of blinatumomab immunotherapy is not dependent on T cells with a specific TCR or on peptide antigens presented by tumor cells. However, it is polyclonal in nature and independent of human leukocyte antigen (HLA) molecules on target cells. Blinatumomab mediates the formation of a cytolytic synapse between the T cell and the tumor cell, resulting in the release of proteolytic enzymes that destroy both proliferating and quiescent target cells. Blinatumomab is associated with transient upregulation of cell adhesion molecules, production of cytolytic proteins, release of inflammatory cytokines, and proliferation of T cells, resulting in elimination of CD19+/ cells.

The adverse effects described in this section were identified in clinical trials in patients with B-precursor ALL (N = 1,045).

The most common adverse effects were: Pyrexia (70.8%), Infections - pathogen not specified (41.4%), Infusion-related reactions (33.4%), Headache (32.7%), Nausea (23.9%), Anemia (23.3%), Thrombocytopenia (21,6%), edema (21.4%), neutropenia (20.8%), febrile neutropenia (20.4%), diarrhea (19.7%), vomiting (19.0%), exanthema (18.0%), elevated liver enzymes (17.2%), cough (15.0%), bacterial infections (14.1%), tremor (14.1%), cytokine release syndrome (13.8%), leukopenia (13.8%), constipation (13.5%), decreased immunoglobulin levels (13.4%), viral infections (13,3%), hypotension (13.0%), back pain (12.5%), chills (11.7%), abdominal pain (10.6%), tachycardia (10.6%), insomnia (10.4%), limb pain (10.1%), and fungal infections (9.6%).

BLINCYTO®

1. Locatelli F et al (2021) Effect of Blinatumomab vs Chemotherapy on Event-Free Survival Among Children With High-risk First-Relapse B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA 325: 843-854.
2. Nagorsen D et al (2012) linatumomab: a historical perspective. Pharmacol Ther 136:334-342.