Blinatumomab
Mechanism :
Blinatumomab is a bispecific T-cell engager (BiTE) which binds to CD19 expressed on B-cells and CD3 expressed on T-cells.
It activates endogenous T cells by connecting CD3 in the T-cell receptor complex with CD19 on B-cells (malignant and benign), thus forming a cytolytic synapse between a cytotoxic T-cell and the cancer target B-cell.
Indication :
- Treatment of relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)
- Treatment of B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) ≥0.1%
Contraindications :
Known hypersensitivity to blinatumomab or any component of the formulation.
Dosing :
Acute lymphoblastic leukemia (B-cell precursor), MRD-positive (≥0.1%):
IV:
Each induction or consolidation treatment cycle consists of 4 weeks of continuous infusion followed by a 2-week treatment-free interval (allow at least 2 weeks treatment-free between cycles). Therapy involves 1 induction cycle followed by up to 3 additional cycles for consolidation (total of up to 4 cycles).
Patients <45 kg (dose based on BSA):
Cycles 1 to 4: 15 mcg/m²/day (Maximum: 28 mcg/day) as a continuous infusion on days 1 to 28 of a 6-week treatment cycle
Patients ≥45 kg (fixed dose):
Cycles 1 to 4: 28 mcg daily administered as a continuous infusion on days 1 to 28 of a 6-week treatment cycle.
Acute lymphoblastic leukemia (B-cell precursor), relapsed/refractory:
IV:
Each induction or consolidation treatment cycle consists of 4 weeks of continuous infusion followed by a 2-week treatment-free interval (allow at least 2 weeks treatment-free between cycles). Each continued therapy cycle consists of 4 weeks of continuous infusion followed by an 8-week treatment-free interval. Therapy involves 2 induction cycles followed by 3 additional cycles for consolidation and up to 4 additional cycles of continued therapy (total of up to 9 cycles).
Patients <45 kg (dose based on BSA):
Cycle 1:
5 mcg/m²/day (Maximum: 9 mcg/day) administered as a continuous infusion on days 1 to 7, followed by 15 mcg/m²/day (Maximum: 28 mcg/day) as a continuous infusion on days 8 to 28 of a 6-week treatment cycle.
Cycles 2 through 5:
15 mcg/m²/day (Maximum: 28 mcg/day) administered as a continuous infusion on days 1 to 28 of a 6-week treatment cycle.
Cycles 6 through 9:
15 mcg/m²/day (Maximum: 28 mcg/day) administered as a continuous infusion on days 1 to 28 of a 12-week treatment cycle.
Patients ≥45 kg (fixed dose):
Cycle 1:
9 mcg daily administered as a continuous infusion on days 1 to 7, followed by 28 mcg daily as a continuous infusion on days 8 to 28 of a 6-week treatment cycle.
Cycles 2 through 5:
28 mcg daily administered as a continuous infusion on days 1 to 28 of a 6-week treatment cycle.
Cycles 6 through 9:
28 mcg daily administered as a continuous infusion on days 1 to 28 of a 12-week treatment cycle.
Adverse Effect :
Edema, hypotension, arrhythmia, neurotoxicity, headache, chills, insomnia, skin rash, decreased lymphocyte count, neutropenia, anemia, thrombocytopenia, decreased serum immunoglobulins, increased serum transaminases, cytokine release syndrome, infection, bacteremia, opportunistic infections, sepsis, catheter infection, tremor, pneumonia, cough, fever, infusion related reaction, septic shock, antibody development.
Interaction :
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone.
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide.
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib.
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines.
Hepatic Dose :
Baseline hepatic impairment: No dosage adjustments are recommended.
Hepatic impairment during therapy: Interrupt blinatumomab therapy if AST/ALT increase > 5 times the upper limit of normal (ULN) or if bilirubin increases > 3 times the ULN.