Introduction
Blincyto (blinatumomab) is a bispecific CD19-directed CD3 T-cell engager approved by the FDA for the treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). This innovative immunotherapy represents a significant advancement in targeted cancer treatment, harnessing the body's own immune system to fight malignant cells.
Mechanism of Action
Blincyto is a bispecific T-cell engager (BiTE) antibody construct that simultaneously binds to CD19 expressed on the surface of B-lineage cells and CD3 expressed on the surface of T-cells. This dual binding facilitates the formation of a cytolytic synapse between T-cells and target cells, leading to T-cell activation, proliferation, and subsequent lysis of CD19+ cells through perforin and granzyme-mediated apoptosis.
Indications
- Treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adults and children
- Minimal residual disease (MRD)-positive B-cell precursor ALL in adults and children who are in first or second complete remission
Dosage and Administration
Standard dosing:- Cycle 1: 9 mcg/day continuous IV infusion for first 7 days, then 28 mcg/day for remaining days
- Subsequent cycles: 28 mcg/day continuous IV infusion for 28 days
- Each treatment cycle consists of 4 weeks of continuous infusion followed by a 2-week treatment-free interval
- Administered as continuous intravenous infusion over 24-96 hours using a portable infusion pump
- Premedication with dexamethasone recommended to mitigate cytokine release syndrome
- Requires hospitalization for at least the first 9 days of the first cycle and the first 2 days of the second cycle
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No specific recommendations available
- Pediatric: Safety established in children ≥1 year old
Pharmacokinetics
Absorption: Administered intravenously with 100% bioavailability Distribution: Volume of distribution approximately 4.52 L Metabolism: Primarily proteolytic degradation into small peptides and amino acids Elimination: Half-life approximately 2.11 hours; primarily cleared through T-cell mediated target cell elimination Steady-state: Achieved within 24 hours of continuous infusionContraindications
- Hypersensitivity to blinatumomab or any component of the formulation
- Active, uncontrolled infection requiring systemic therapy
Warnings and Precautions
Boxed Warning:- Cytokine Release Syndrome (CRS): May be life-threatening or fatal; requires close monitoring and management
- Neurological Toxicities: Including encephalopathy, seizures, speech disorders, and disturbances in consciousness
- Infections: Increased risk of serious and sometimes fatal infections
- Tumor Lysis Syndrome: Monitor patients with high tumor burden
- Pancreatitis: Fatal cases have been reported
- Leukopenia: Increased risk during the first treatment cycle
- Preparation and administration errors: Requires specific training due to complex dosing schedule
Drug Interactions
- Immunosuppressants: May diminish therapeutic effects
- Live vaccines: Avoid concurrent administration
- CYP450 substrates: Potential for altered metabolism due to cytokine-mediated effects on hepatic enzymes
Adverse Effects
Very common (>10%):- Pyrexia (62%)
- Headache (36%)
- Peripheral edema (25%)
- Nausea (25%)
- Hypokalemia (23%)
- Constipation (20%)
- Diarrhea (20%)
- Fatigue (20%)
- Rash (15%)
- Tremor (15%)
- Cytokine release syndrome (15%)
- Neurological toxicities (50%)
- Infections (25%)
- Tumor lysis syndrome (<1%)
- Pancreatitis (<1%)
Monitoring Parameters
Prior to initiation:- Complete blood count with differential
- Comprehensive metabolic panel
- Neurological assessment
- Infection screening
- Daily monitoring for signs of CRS (fever, hypoxia, hypotension) during first week
- Frequent neurological assessments
- CBC weekly or more frequently if indicated
- Liver function tests periodically
- Signs and symptoms of infection
- Tumor lysis syndrome monitoring in high-risk patients
- Long-term neurological follow-up
- Immune reconstitution monitoring
- Minimal residual disease assessment
Patient Education
- Understand the signs and symptoms of cytokine release syndrome (fever, chills, difficulty breathing) and neurological toxicity (confusion, seizures, speech problems)
- Report any signs of infection immediately
- Adhere to scheduled monitoring appointments
- Understand the importance of continuous infusion and proper pump operation
- Avoid driving or operating heavy machinery if experiencing neurological symptoms
- Discuss vaccination status with healthcare provider before initiation
- Use effective contraception during treatment and for at least 48 hours after final dose
References
1. FDA Prescribing Information: Blincyto (blinatumomab) 2. Kantarjian H, et al. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017;376(9):836-847 3. Topp MS, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16(1):57-66 4. NCCN Guidelines: Acute Lymphoblastic Leukemia (Version 2.2023) 5. Brown PA, et al. Pediatric Acute Lymphoblastic Leukemia, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020;18(1):81-112
This monograph is intended for educational purposes only and should not replace clinical judgment. Always consult current prescribing information and clinical guidelines.