Formulation and Specifications: Powder injection: 35 μg/vial, plus 1 vial of 10 ml intravenous infusion solution stabilizer
Indications: Indicated in adults with relapsed or refractory precursor B-cell acute lymphoblastic leukemia.
Key points for rational drug use:
1. Therapeutic dose: Patients with ≥45 kg body weight receive fixed dose administration, and patients with <45 kg body weight receive dose calculation based on body surface area. Patients with refractory and relapsing disease need to start at a low dose on days 1-7 of the first treatment cycle, with a fixed dose of 9 μg/d for those weighing ≥45 kg and 5 μg/(m2-d) for those <45 kg based on body surface area; increase to the full dose from day 8 to day 28, i.e. 28 μg/d for those ≥45 kg and 15 μg/(m2-d for those <45 kg. 15 μg/(m2-d) for 45 kg. For patients with positive small residual lesions, no dose creep is required and the full dose of 28 μg/d (≥45 kg) or 15 μg/(m2-d) (<45 kg) is given at the start. In case of interruption of dosing (e.g., due to adverse events) during treatment, the cycle can be continued for less than 7 days until a total of 28 days of infusion, and a new cycle of treatment will be restarted if interruption of dosing exceeds 7 days.
2. Treatment course: The course of treatment for patients with refractory and relapsing disease consists of up to 2 cycles of induction therapy, followed by 3 cycles of consolidation therapy and up to 4 cycles of sequential continuous therapy. treatment interval (84 days in total).
3. Dexamethasone premedication: For adult patients, 20 mg of dexamethasone is premedicated 1 hour prior to the first dose in each cycle of the product, prior to a higher dose (e.g., Cycle 1, Day 8), and when restarting infusion after a treatment interruption of 4 hours or more.
4. Pre-treatment of patients with high tumor load: Treatment with dexamethasone (no more than 24 mg/d) for patients with ≥50% primitive cells in the bone marrow or peripheral blood primitive cell counts >15×109/L.
5. Intrathecal prophylactic chemotherapy prior to and during treatment with this product to prevent relapse of CNS acute lymphoblastic leukemia.
6. No dose adjustment is required in patients with mild to moderate renal impairment. There is no information on the pharmacokinetics of belintumomab in patients with severe renal impairment (creatinine clearance <30 ml/min) or who are on hemodialysis.
7. The transient release of cytokines resulting from the initiation of treatment with belintumomab may inhibit CYP450 enzymes. The risk of drug interactions is highest during the first 9 days of cycle 1 and the first 2 days of cycle 2 in patients on combined CYP450 substrates, particularly those with narrow therapeutic indices. Toxicity (e.g., warfarin) or drug concentrations (e.g., cyclosporine) should be monitored in these patients.
8. Cytokine release syndrome: Cytokine release syndrome was reported in 15% of patients with relapsed or refractory acute lymphoblastic leukemia and 7% of patients with microresidue positive acute lymphoblastic leukemia in clinical trials. The median time to onset of cytokine release syndrome was 2 days after the start of infusion, and the median time to resolution of cytokine release syndrome was 5 days. Manifestations of cytokine release syndrome include fever, headache, nausea, malaise, hypotension, elevated ALT, elevated AST, elevated total bilirubin, and disseminated intravascular coagulation. The manifestations of cytokine release syndrome after treatment with belintuzumab overlap with those of infusion reactions, capillary leak syndrome, and phagocytic histiocytosis/macrophage activation syndrome. Most cytokine release syndromes are reversible and can be prevented by identifying high-risk patients, dexamethasone premedication, and gradual dose increases prior to belintumomab administration. Low-grade (grade 1 to 2) cytokine release syndrome does not require suspension of belintuzumab and can be treated symptomatically with close monitoring of relevant indicators and vital signs. For severe (≥ grade 3) cytokine release syndrome, grade 3 requires suspension of drug administration and grade 4 requires permanent discontinuation and close monitoring of vital signs and prompt active treatment with glucocorticoids (dexamethasone preferred) and IL-6 receptor blockers according to clinical indications.
9. Neurological toxicity: Neurological toxicity occurred in approximately 65% of patients in clinical trials. The median time to first event was within the first 2 weeks of treatment with this product, and most neurological events could subside. The most common (≥10%) manifestations of neurologic toxicity were headache and tremor; the characteristics of neurologic toxicity varied by age group. Grade ≥3 (severe, life-threatening, or resulting in death) neurologic toxicity, including encephalopathy, seizures, speech impairment, impaired consciousness, disorientation, coordination, and balance, occurred in approximately 13% of patients after initiation of this drug. Manifestations of neurologic toxicity include cranial nerve disorders. All grade ≥3 neurologic toxicities should be suspended from dosing and subjected to physical examination, monitoring of vital signs, and safety-related laboratory tests, while dexamethasone therapy is administered at a maximum dose of no more than 24 mg/d per day, depending on the patient’s condition, and dexamethasone dose reduction should be completed within 4 days until discontinuation. Supportive therapy such as antiepileptic drugs for seizures should be considered at the discretion of the specialist.
*10. Other treatments: belintuzumab can be used in adult and pediatric patients with CR1 or CR2 with microresidue positive acute lymphoblastic leukemia, as well as in pediatric relapsed or refractory precursor B-cell acute lymphoblastic leukemia (an approved indication in other countries worldwide). Also available in combination with the second-generation tyrosine kinase inhibitor dasatinib in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Phase II clinical study) and in combination with the third-generation tyrosine kinase inhibitor bonatinib in newly diagnosed and relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Phase II clinical study).