Blincyto

Blinatumomab Instructions

Generic name: blinatumomab
Trade name: Blincyto
Full names: blinatumomab, Blinatumomab, Blincyto

Indications:
Indicated for the treatment of Philadelphia chromosome-negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

Usage and Dosage:
Usage:
(1) The treatment process includes 2 cycles of induction therapy, followed by 3 cycles of consolidation therapy and 4 cycles of continuous therapy.
(2) A single cycle of induction or consolidation therapy consists of 28 days of continuous intravenous infusion followed by a 14-day interval (42 days in total).
(3) A single cycle of maintenance therapy consists of 28 days of continuous intravenous infusion followed by a 56-day interval (84 days in total).
It is recommended to be hospitalized for the first 9 days of the first course of treatment and the first two days of the second course of treatment.
Pretreatment with dexamethasone is required before use.
Dosage:
(1) Induction therapy: Patients ≥45kg should be given 9 μg/day on days 1-7 of the first course of treatment, and 28 μg/day on days 8-28; subsequent courses of treatment should be 28 μg/day on days 1-28; patients <45kg should be given 5 μg/day on days 1-7 of the first course of treatment. mcg/㎡/day, and 15mcg/㎡/day on days 8-28; for subsequent courses of treatment, 15mcg/㎡/day on days 1-28;
(2) Consolidation and maintenance treatment: for patients ≥45kg, 28μg/day on days 1-28; for patients <45kg, 15mcg/㎡/day on days 1-28.
Use an intravenous pump to ensure a constant flow rate for continuous intravenous infusion therapy.

Adverse reactions:
>10%:
Cardiovascular diseases: edema (18%), hypotension (≤14%), arrhythmia (12%-14%)
Central nervous system: Neurotoxicity (65%), headache (23%-39%), chills (≤28%), insomnia (≤18%), aphasia (≤12%)
Dermatology: rash (12%-16%)
Blood and tumors: decreased absolute lymphocyte count (grade 3 or 4: 80%), neutropenia (15%-31%; grade ≥3: 15%-28%), anemia (≤25%; grade ≥3: 19%), thrombocytopenia Decreased platelets (10%-21%; grade ≥3: 6%-18%), decreased serum immunoglobulins (≤18%; may include IgA, IgG, IgM), leukopenia (8%-14%; grade ≤3: 7 %-9%)
Liver: elevated serum aminotransferase (9%-15%), elevated serum ALT (alanine aminotransferase) (Grade 3/4: 11%)
Hypersensitivity: cytokine release syndrome (7%) -15%)
Infection: infection (28%-39%), bacteremia (≤25%), opportunistic infection (≤25%), sepsis (≤25%), severe infection (≤25%), bacterial infection (≤1 4%), viral infection (≤11%)
Local reaction: Catheter infection (≤25%)
Neuromuscular and skeletal: Tremor (<31%; may include essential tremor, intentional tremor, resting tremor) , back pain (<12%)
Respiratory system: pneumonia (≤25%), cough (13%)
Others: fever (55%-91%), infusion-related reactions (30%-77%)
1% -10%:
Cardiovascular: septic shock (≥2%)
Central nervous system: brain disease (<10%), dizziness (>10%), epilepsy (≥2%)
Endocrine metabolism: weight gain (≤10%)
Hematology and tumors: febrile neutropenia (≥2%)
Liver: elevated serum AST (aspartate aminotransferase) (Grade 3/4: 8%), elevated serum bilirubin (Grade 3/4: 5%)
Immune: Antibody development (<2%; most neutralized)
Infections: Fungal infections (≤10%), Staphylococcal infections (≥2%)
Undefined frequency:
Cardiovascular: Capillary leak syndrome, chest discomfort, chest pain, circulatory shock, flushing, hypertension, hypertensive crisis, peripheral edema
Central nervous system: mental status changes, cognitive dysfunction, confusion, cranial nerve dysfunction (including facial nerve disorder, trigeminal nerve disorder), depression, attention disorder, coordination disorder, drowsiness, balance disorder, facial paresis, hyperthermia, hypoesthesia, consciousness disorder, memory loss, non-cardiac chest pain, pain, sixth nerve palsy, speech disorder, suicidal ideation
Dermatology: atopic dermatitis, erythema multiforme , urticaria
Endocrine metabolism: hot flashes, hypovolemic shock
Hematology and neoplasms: hematological abnormalities (phagocytic histiocytosis), hypogammaglobulinemia, leukocytosis, lymphadenopathy, tumor lysis syndrome
Liver: elevated serum alkaline phosphatase

Contraindications:
Hypersensitivity to blinatumomab or any ingredient in the product formulation.

Precautions:
Myelosuppression: Neutropenia, including life-threatening episodes, has been reported. Monitor blood counts throughout treatment; treatment interruption may be necessary if prolonged neutropenia occurs. Anemia and thrombocytopenia may also occur.
Hepatotoxicity: Transient elevations in liver enzymes (related to or not related to CRS (Cardiorenal Syndrome Type I)) may occur during treatment. In patients with acute lymphoblastic leukemia (ALL), the median time to enzyme elevation is 3-19 days; grade 3 or higher elevations have been observed in a minority of patients. Monitor ALT, AST, GGT, and total bilirubin at baseline and during treatment. Interrupt treatment if transaminases are greater than 5 times ULN (upper limit of normal) or total bilirubin is greater than 3 times ULN (upper limit of normal).
Infections: Approximately one-quarter of patients in clinical trials reported serious infections (which could be life-threatening or fatal), such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-related infections. Consider prophylactic antibiotics when appropriate and monitor closely for signs/symptoms of infection. If there is an infection, it should be treated promptly.
Leukoencephalopathy: Leukoencephalopathy (as seen on MRI) has been reported, particularly in patients treated with cranial irradiation and antileukemic chemotherapy (eg, high-dose methotrexate, intrathecal cytarabine).
Pancreatitis: Fatal cases of pancreatitis have been reported in patients receiving blinatumomab plus dexamethasone during post-marketing therapy. Monitor for signs/symptoms of pancreatitis; interruption or discontinuation of treatment may be necessary.
Tumor Lysis Syndrome: Life-threatening or fatal tumor lysis syndrome (TLS) has been observed. Implement measures to prevent TLS (e.g., pretreatment nontoxic cytoreduction and hydration during treatment). Monitor for signs/symptoms of TLS (e.g., acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia); interruption or discontinuation of treatment may be necessary.
Vaccines: Live virus vaccines are not recommended for at least 2 weeks before starting blinatumomab, during treatment, and until the immune system has recovered after the last cycle of treatment.
Effects on ability to drive and use machinery: Advise patients not to drive and engage in hazardous occupations or activities, such as operating heavy or potentially hazardous machinery, while taking blinatumomab.
Risk of Serious Adverse Reactions in Pediatrics Due to Benzyl Alcohol Preservative: In patients weighing less than 22 kg, use blinatumomab in preservative-free saline.

Storage:
Store blinatumomab and IV (intravenous bolus) solution stabilizer vials in the original packaging refrigerated at 2°C to 8°C (36°F to 46°F) and protected from light until use. Do not freeze. Blinatumomab and IV (intravenous bolus) solution stabilizer vials can be stored in the original carton for up to 8 hours at room temperature 23°C to 27°C (73°F to 81°F), protected from light.
Mechanism of Action:
Blinatumomab is a bispecific CD19-CD3 T-cell adapter that binds to CD19 expressed on the surface of cells of B-lineage origin and to CD3 expressed on the surface of T cells. Endogenous T cells are activated by ligation of CD3 on the T-cell receptor (TCR) complex with CD19 on benign and malignant B cells. Blinatumomab mediates the formation of synapses between T cells and tumor cells, the upregulation of cell adhesion molecules, the production of cytolytic proteins, the release of inflammatory cytokines, and the proliferation of T cells, leading to the redirection of CD19+ cells to lysis.
Safety and efficacy:
Blinatumomab (Blinatumomab) is a bispecific CD19-directed CD3 T-cell engagement immunotherapy that combines CD19 expressed on the surface of B-cell-derived cells and CD3 expressed on the surface of T cells. Blinatumomab is the first and only approved T-cell engagement (BiTE) immunotherapy for the treatment of ALL (leukemia) and MRD (minimal residual disease).
In a single-arm clinical study, blinatumomab demonstrated good efficacy in the treatment of patients with MRD (minimal residual disease)-positive ALL (leukemia). These patients have had 1 or 2 complete remissions, but there are still cancer cells remaining in the bone marrow, accounting for about one thousandth of the total number of cells. After treatment, even a high-precision test that can pick out 1 cell out of 10,000 cells was unable to detect MRD (minimum residual disease) in the patient's body, confirming the effect of blinatumomab. Overall, 70% of patients can no longer detect MRD (minimal residual disease), and more than half of patients have survived in remission for 22.3 months.