Blincyto

Adult & ped patients ≥1 mth w/ CD19 +ve B-cell precursor acute lymphoblastic leukemia (ALL) in 1st or 2nd complete remission w/ minimal residual disease (MRD) ≥0.1%; relapsed or refractory CD19 +ve B-cell precursor ALL; CD19 +ve Philadelphia chromosome -ve B-cell precursor ALL in consolidation phase of multiphase chemotherapy.

IV infusion Intrathecal chemotherapy prophylaxis before & during therapy to prevent CNS ALL relapse is recommended. MRD +ve B-cell precursor ALL 1 cycle for induction followed by up to 3 additional cycles for consolidation. Single induction or consolidation cycle: 28 days of continuous IV infusion followed by 14 days treatment-free interval (total of 42 days). Patient weighing ≥45 kg Induction cycle 1 & consolidation cycles 2-4 (fixed-dose): 28 mcg daily on days 1-28; 14-day treatment-free interval on days 29-42. Patient weighing <45 kg Induction cycle 1 & consolidation cycles 2-4 (BSA-based dose): 15 mcg/m² daily (Max: 28 mcg daily) on days 1-28; 14-day treatment-free interval on days 29-42. Premed: Adult Prednisone 100 mg IV or equiv (eg, dexamethasone 16 mg) 1 hr prior to 1st dose in each cycle. Ped Dexamethasone 5 mg/m² (Max dose: 20 mg) IV or oral prior to 1st dose in 1st cycle & when restarting infusion after ≥4 hr interruption in 1st cycle. Relapsed or refractory B-cell precursor ALL 2 induction cycles followed by 3 additional cycles for consolidation & up to 4 additional cycles of continued therapy. Single induction or consolidation cycle: 28 days continuous IV infusion followed by 14 days treatment-free interval (total of 42 days). Single cycle of continued therapy: 28 days of continuous IV infusion followed by 56 days treatment-free interval (total of 84 days). Patient weighing ≥45 kg Induction cycle 1 (fixed-dose): 9 mcg daily on days 1-7; 28 mcg daily on days 8-28; 14-day treatment-free interval on days 29-42. Induction cycle 2 & consolidation cycles 3-5 (fixed dose): 28 mcg daily on days 1-28; 14-day treatment-free interval on days 29-42. Continued therapy cycles 6-9 (fixed dose): 28 mcg daily on days 1-28; 56-day treatment free interval on days 29-84. Patient weighing <45 kg Induction cycle 1 (BSA-based dose): 5 mcg/m² daily (Max: 9 mcg daily) on days 1-7; 15 mcg/m² daily (Max: 28 mcg daily) on days 8-28; 14-day treatment-free interval on days 29-42. Induction cycle 2 & consolidation cycles 3-5 (BSA-based dose): 15 mcg/m² daily (Max: 28 mcg daily) on days 1-28; 14-day treatment-free interval on days 29-42. Continued therapy cycles 6-9 (BSA-based dose): 15 mcg/m² daily (Max: 28 mcg daily) on days 1-28; 56-day treatment-free interval on days 29-84. Premed: Adult Dexamethasone 20 mg IV or oral 1 hr prior to 1st dose of each cycle, prior to step dose (eg, cycle 1 day 8) & when restarting infusion after interruption of ≥4 hr. Ped Dexamethasone 5 mg/m² (Max dose: 20 mg) IV or oral prior to 1st dose in 1st cycle, prior to step dose (eg, cycle 1 day 8), & when restarting infusion after interruption of ≥4 hr in 1st cycle. B-cell precursor ALL in the consolidation phase Single consolidation cycle: 28 days continuous IV infusion followed by 14-day treatment-free interval (total 42 days). Patient weighing ≥45 kg Fixed dose: 28 mcg daily on days 1-28; 14-day treatment-free interval on days 29-42. Patient weighing <45 kg BSA-based dose: 15 mcg/m² daily (Max: 28 mcg daily) on days 1-28; 14-day treatment-free interval on days 29-42. Premed: Adult Dexamethasone 20 mg IV 1 hr prior to 1st dose of each cycle. Ped Dexamethasone 5 mg/m² (Max dose: 20 mg) IV or oral prior to 1st dose in 1st cycle & when restarting infusion after interruption of ≥4 hr in 1st cycle.

Hypersensitivity.

Discontinue permanently in life-threatening cytokine release syndrome (CRS). Interrupt or discontinue use if neurological toxicities including immune effector cell-associated neurotoxicity syndrome (ICANS) or tumor lysis syndrome (TLS) occurs. Interrupt treatment if severe CRS or prolonged neutropenia occurs; in transaminases >5x ULN or bilirubin >3x ULN. Higher risk of seizures in patients >10 yr w/ down syndrome. Leukoencephalopathy, especially in patients w/ prior treatment w/ cranial irradiation & antileukemic chemotherapy including systemic high-dose MTX or intrathecal cytarabine. Patients w/ active ALL in CNS or history of neurologic events; history or presence of clinically relevant CNS pathology. Monitor for signs & symptoms of CRS, neurological toxicities including ICANS, infections, TLS, pancreatitis; lab parameters (eg, WBC & ANC) during infusion; ALT, AST, γ-glutamyl transferase & total blood bilirubin prior to start of & during treatment. Administer corticosteroids for severe or life-threatening CRS; prophylactic antibiotics for serious infections; pretreatment nontoxic cytoreduction & on treatment hydration during treatment for prevention of TLS. Not recommended w/ concomitant vaccination w/ live virus for at least 2 wk prior to start of & during treatment, & until immune recovery following last cycle. Refrain from driving & engaging in hazardous occupations or activities eg, operating heavy or potentially dangerous machinery. Females of reproductive potential should use contraception during treatment & at least 48 hr after last dose. May cause fetal harm to pregnant woman. Verify pregnancy status of females of reproductive potential prior to initiating treatment. Not to breastfeed during & for 48 hr last dose. Ped patients <1 mth. Elderly.

Neutropenia, leukopenia, thrombocytopenia, anemia, lymphopenia, febrile neutropenia; arrhythmia; pyrexia, chills, edema; unspecified pathogen infections, bacterial/viral/fungal infectious disorders; infusion-related reaction; decreased Ig, increased wt, hypertransaminasemia; back & musculoskeletal pain; headache, tremor, aphasia, dizziness, encephalopathy; insomnia; cough; rash; hypotension, HTN, hemorrhage; CRS, hypogammaglobulinemia; nausea, diarrhea, abdominal pain, stomatitis; abnormal LFT. Fatal pancreatitis.

Concomitant use w/ CYP450 substrates, 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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