Blincyto

Blinatumomab

Monotherapy for the treatment of adults w/ CD19 +ve relapsed or refractory B-precursor acute lymphoblastic leukaemia (ALL). Patients w/ Philadelphia chromosome +ve B-precursor ALL should have failed treatment w/ at least 2 tyrosine kinase inhibitors & have no alternative treatment options. Monotherapy for the treatment of adults w/ Philadelphia chromosome -ve CD19 +ve B-precursor ALL in 1st or 2nd complete remission w/ minimal residual disease (MRD) ≥0.1%. Monotherapy for the treatment of paed patients ≥1 yr w/ Philadelphia chromosome -ve CD19 +ve B-precursor ALL which is refractory or in relapse after receiving at least 2 prior therapies or in relapse after receiving prior allogeneic haematopoietic stem cell transplantation. Monotherapy for the treatment of paed patients ≥1 yr w/ high-risk 1st relapsed Philadelphia chromosome -ve CD19 +ve B-precursor ALL as part of the consolidation therapy.

Relapsed or refractory B-precursor ALL May receive 2 treatment cycles followed by 3 additional consolidation treatment cycles based on an individual benefits-risks assessment. Single cycle treatment: Continuous infusion for 28 days. Each cycle of treatment is separated by a 14-day treatment-free interval. Patient ≥45 kg (fixed-dose) Cycle 1: 9 mcg/day on days 1-7; 28 mcg/day on days 8-28. Allow a 14-day treatment-free interval between cycles. Subsequent cycles: 28 mcg/day on days 1-28, followed by a 14-day treatment-free interval on days 29-42. <45 kg (BSA-based dose) Cycle 1: 5 mcg/m²/day (not to exceed 9 mcg/day) on days 1-7; 15 mcg/m²/day (not to exceed 28 mcg/day) on days 8-28. Allow a 14-day treatment-free interval between cycles. Subsequent cycles: 15 mcg/m²/day (not to exceed 28 mcg/day) on days 1-28, followed by a 14-day treatment-free interval on days 29-42. High-risk 1st relapsed B-precursor ALL Paed patient May receive 1 cycle of Blincyto treatment after induction & 2 blocks of consolidation chemotherapy. Single cycle treatment: Continuous infusion for 28 days. ≥45 kg (fixed-dose) 1 consolidation cycle: 28 mcg/day on days 1-28. <45 kg (BSA-based dose) 1 consolidation cycle: 15 mcg/m²/day (not to exceed 28 mcg/day) on days 1-28. Premed & additional medication: Anti-pyretic use (eg, paracetamol) is recommended to reduce pyrexia during the 1st 48 hr of each treatment cycle. Intrathecal chemotherapy prophylaxis is recommended before & during Blincyto therapy to prevent CNS ALL relapse. Adult Dexamethasone 20 mg IV, administered 1 hr prior to initiation of each cycle of Blincyto therapy. Paed patient Dexamethasone 10 mg/m² (not to exceed 20 mg) administered orally or intravenously 6-12 hr prior to the start of Blincyto (cycle 1, day 1) followed by dexamethasone 5 mg/m² orally or intravenously w/in 30 min prior to the start of Blincyto (cycle 1, day 1). Pre-phase treatment: Patient w/ ≥50% leukaemic blasts in bone marrow or >15,000/microlitre peripheral blood leukaemic blast counts Treat w/ dexamethasone (not to exceed 24 mg/day). MRD +ve B-precursor ALL May receive 1 cycle of induction treatment followed by up to 3 additional cycles of Blincyto consolidation treatment. Single induction or consolidation cycle: Continuous IV infusion for 28 days followed by a 14-day treatment-free interval (total of 42 days). Patient at least 45 kg Induction cycle 1 & consolidation cycles 2-4: 28 mcg/day on days 1-28; followed by a 14-day treatment-free interval on days 29-42. Premed & additional medication: Prednisone 100 mg IV or equiv (eg, dexamethasone 16 mg), administered 1 hr prior to initiation of each cycle of Blincyto therapy. Anti-pyretic use (eg, paracetamol) is recommended to reduce pyrexia during the 1st 48 hr of each treatment cycle. Intrathecal chemotherapy prophylaxis is recommended before & during Blincyto therapy to prevent CNS ALL relapse.

Hypersensitivity. Breast-feeding.

Perform neurological exam prior to start of therapy. Monitor patients for signs & symptoms of neurologic events, infection, cytokine release syndrome (CRS), infusion reactions, tumor lysis syndrome (TLS), pancreatitis; management of these events may require temporary interruption or discontinuation of treatment. Cases of neutropenia & febrile neutropenia have been observed; lab parameters (eg, WBC & ANC) should be monitored routinely during infusion. Monitor ALT, AST, γ-glutamyl transferase & total blood bilirubin prior to the start of & during treatment. Cranial MRI changes showing leukoencephalopathy have been observed. CD19 -ve B-precursor ALL has been reported in relapsed patients receiving the treatment. All relapsed patients should be monitored for presence of AML. Not recommended for vaccination w/ live virus vaccine for at least 2 wk prior to start of treatment, during treatment, & until immune recovery following the last cycle. Refrain from driving & engaging in hazardous occupations or activities eg, operating heavy or potentially dangerous machinery. Safety & efficacy have not been studied in patients w/ severe renal &/or hepatic impairment. Women of childbearing potential should use effective contraception during treatment & at least 48 hr after treatment. Not to be used during pregnancy unless the potential benefit outweighs the potential risk to the foetus. Do not breastfeed during & for at least 48 hr after treatment. Safety & efficacy in childn <1 yr have not yet been established. Limited experience in elderly ≥75 yr.

Bacterial/viral/unspecified pathogen infections; febrile neutropenia, anaemia, neutropenia, thrombocytopenia, leukopenia; CRS; insomnia; headache, tremor; tachycardia; hypotension, HTN; cough; nausea, diarrhoea, vomiting, constipation, abdominal pain; rash; back pain, pain in extremity; pyrexia, chills, oedema; increased hepatic enzyme, decreased Ig; infusion-related reactions. Sepsis, pneumonia, fungal infections; leukocytosis, lymphopenia; hypersensitivity; TLS; confusional state, disorientation; encephalopathy, aphasia, paraesthesia, seizure, cognitive disorder, memory impairment, dizziness, somnolence, hypoaesthesia, cranial nerve disorder, ataxia; flushing; dyspnoea, productive cough, resp failure, wheezing; hyperbilirubinaemia; bone pain; chest pain, pain; increased wt, increased blood alkaline phosphatase.

May suppress CYP450 enzymes, particularly those w/ narrow therapeutic index.

Targeted Cancer Therapy

L01FX07 - blinatumomab ; Belongs to the class of other monoclonal antibodies and antibody drug conjugates. Used in the treatment of cancer.

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