Introduction to Blinatumomab

Blinatumomab (trade name: Blincyto) is a bispecific T-cell engager (BiTE) antibody construct used in the treatment of certain types of leukemia. It was approved by the FDA in 2014 for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Mechanism of Action

Blinatumomab works by simultaneously binding to CD19 (expressed on B cells) and CD3 (expressed on T cells). This binding action:

• Brings CD3-positive T cells into close proximity with CD19-positive B cells
• Activates endogenous T cells by connecting the CD3 in the T-cell receptor complex with CD19 on benign and malignant B cells
• Induces T-cell activation, proliferation, and release of inflammatory cytokines and cytolytic proteins
• Results in redirected lysis of CD19-positive cells

Indications

Blinatumomab is indicated for the treatment of:

• Adults and children with B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%
• Adults and children with relapsed or refractory B-cell precursor ALL

It's particularly useful in pediatric patients with relapsed/refractory ALL who have limited treatment options.

Administration

Blinatumomab is administered as a continuous intravenous infusion:

• For MRD-positive B-cell precursor ALL: 28-day treatment cycles with 4 weeks on and 2 weeks off
• For Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL: 6-week treatment cycles
• Dosing is weight-based, with different regimens for patients ≥45 kg and <45 kg
• Hospitalization is recommended for the first 3 days of the first cycle and first 2 days of the second cycle

Adverse Effects

Common adverse effects include:

• Cytokine release syndrome (CRS)
• Neurological toxicities
• Infections
• Fever
• Headache
• Neutropenia
• Anemia
• Thrombocytopenia

Serious adverse events can include:

• Neurological toxicities (including seizures, encephalopathy, and confusion)
• Severe CRS
• Tumor lysis syndrome
• Neutropenia and febrile neutropenia

Monitoring

Patients receiving blinatumomab should be closely monitored for:

• Signs and symptoms of CRS and neurological toxicities
• Complete blood counts with differentials
• Liver enzymes and renal function
• Signs of infection
• Tumor lysis syndrome (especially at initiation of therapy)

Prophylactic measures include:

• Premedication with dexamethasone to reduce the risk of CRS
• Antiepileptic drugs to prevent seizures in patients with a history of seizures or CNS disorders