Leukemias, lymphomas, and other hematologic cancers:

Indications for: BLINCYTO

CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) ≥0.1%. Relapsed or refractory CD19-positive B-cell precursor ALL.

Clinical Trials:

MRD-positive B-cell Precursor ALL 

BLAST Study

  • The efficacy of Blincyto was evaluated in an open-label, multicenter, single-arm study which included 86 patients 18 years of age and older who had received at least 3 chemotherapy blocks of standard ALL therapy, were in hematologic complete remission (defined as <5% blasts in bone marrow, ANC > 1 Gi/L, platelets > 100 Gi/L) and had minimal residual disease (MRD) at a level of ≥ 0.1% using an assay with a minimum sensitivity of 0.01%.

  • Patients received Blincyto at a constant dose of 15 mcg/m2/day (equivalent to the recommended dosage of 28 mcg/day) intravenously for all treatment cycles. Patients received up to 4 cycles of treatment. The treated population included patients in first or second hematologic complete remission (CR1 or CR2).

  • The efficacy was based on achievement of undetectable MRD within one cycle of Blincyto treatment and hematological relapse-free survival (RFS).

  • 52 of 62 (85.2%; 95%, 73.8-93.0) patients in CR1 achieved complete MRD response. The median hematological relapse-free survival was 35.2 months (range: 0.4 to 53.5). 

  • 18 of 25 (72%; 95% CI, 50.6-87.9) patients in CR2 achieved complete MRD response. The median hematological relapse-free survival was 12.3 months (range: 0.7 to 42.3).

  • Undetectable MRD was achieved by 65 of 80 patients (81.3%; 95% CI, 71.0-89.1) with an assay sensitivity of at least 0.005%. The estimated median hematological RFS among the 80 patients using the higher sensitivity assay was 24.2 months (95% CI: 17.9, NE).

 

Relapsed/Refractory B-cell Precursor ALL

TOWER Study

  • The efficacy of Blincyto was compared to standard of care (SOC) chemotherapy in a randomized, open-label, multicenter study in 405 patients 18 years of age and older with relapsed or refractory B-cell precursor ALL. SOC chemotherapy included fludarabine, cytarabine arabinoside, and granulocyte colony-stimulating factor (FLAG); high-dose cytarabine arabinoside (HiDAC); high-dose methotrexate- (HDMTX) based combination; or clofarabine/clofarabine-based regimens. 

  • Patients were randomly assigned 2:1 received Blincyto (n=271) or investigator-selected SOC chemotherapy (n=134). The efficacy was based on overall survival (OS).

  • The study demonstrated a superior improvement in median OS with Blincyto vs. SOC chemotherapy (7.7 months vs. 4 months, respectively; hazard ratio 0.71 [95% CI, 0.55-0.93]; P =.012).

  • Overall response for complete remission plus complete remission with partial hematologic recovery:

    • 42% (95% CI, 37-49) for Blincyto vs 27% (95% CI, 14-28) for SOC Chemotherapy. Treatment difference of 22% (95% CI, 13-31; P <.001).

  • Overall response for complete remission:

    • 34% (95% CI, 28-40) for Blincyto vs 16% (95% CI, 10-23) for SOC Chemotherapy. Treatment difference of 18% (95% CI, 10-26; P <.001).

 

Study MT103-211 

  • Study MT103-211 was an open-label, multicenter, single-arm study. Eligible patients were ≥ 18 years of age with Philadelphia chromosome-negative relapsed or refractory B-cell precursor ALL. Blincyto was administered as a continuous intravenous infusion to 185 patients. 

  • Efficacy was based on the complete remission (CR) rate, duration of CR, and proportion of patients with an MRD-negative CR/CR with partial hematological recovery (CR/CRh*) within 2 cycles of treatment with Blincyto.

  • CR: 

    • 60 patients (32.4%; 95% CI, 25.7-39.7)

  • CRh: 

    • 17 patients (9.2%; 95% CI, 5.4-14.3)

  • CR/CRh:

    • 77 patients (41.6%; 95% CI, 34.4-49.1)

 

ALCANTARA Study

  • The efficacy of Blincyto for treatment of Philadelphia chromosome-positive B-cell precursor ALL was evaluated in an open-label, multicenter, single-arm study in 45 patients ≥ 18 years of age with Philadelphia chromosome-positive B-cell precursor ALL, relapsed or refractory to at least 1 second generation or later tyrosine kinase inhibitor (TKI), or intolerant to second generation TKI, and intolerant or refractory to imatinib mesylate. 

  • Blincyto was administered at 9 mcg/day on Days 1-7 and 28 mcg/day on Days 8-28 for Cycle 1, and 28 mcg/day on Days 1-28 for subsequent cycles. Efficacy was based on the complete remission (CR) rate, duration of CR, and proportion of patients with an MRD-negative CR/CR with partial hematological recovery (CR/CRh*) within 2 cycles of treatment with Blincyto.

  • CR: 

    • 14 patients (31%; 95% CI, 18-47)

  • CRh: 

    • 2 patients (4%; 95% CI, 1-15)

  • CR/CRh:

    • 16 patients (36%; 95% CI, 22-51)

 

Study MT103-205 

  • Study MT103-205 was an open-label, multicenter, single-arm study in 70 pediatric patients with relapsed or refractory B-cell precursor ALL. Blincyto was administered at 5 mcg/m2/day on Days 1-7 and 15 mcg/m2/day on Days 8-28 for Cycle 1, and 15 mcg/m2/day on Days 1-28 for subsequent cycles.

  • 23 out of 70 (32.9%) patients achieved CR/CRh within the first 2 treatment cycles with 17 out of 23 (73.9%) occurring within Cycle 1 of treatment.  The HSCT rate among those who achieved CR/CRh* was 48% (11 out of 23).

Adults and Children:

Strictly follow preparation and administration instructions. Give by continuous IV infusion at a rate of 10mL/hr over 24hrs, 5mL/hr over 48hrs, or 0.6mL/hr over 7 days (not recommended for patients <22kg). MRD-positive: premedicate with prednisone 100mg IV or equivalent (adults) 1hr prior to 1st dose of each cycle, or dexamethasone 5mg/m2 to max 20mg (pediatrics) prior to 1st dose in the 1st cycle, and when restarting infusion after interruption (≥4hrs). Treat up to 4 cycles (1 cycle for induction, followed by 3 cycles for consolidation). One single cycle = 28 days of continuous IV infusion followed by a 14-day treatment-free interval (during Cycles 1–4). Hospitalization recommended for first 3 days of Cycle 1 and first 2 days of Cycle 2. <45kg (Cycles 1–4): 15mcg/m2/day (max 28mcg/day) on Days 1–28. ≥45kg (Cycles 1–4): 28mcg/day on Days 1–28. Relapsed/refractory: premedicate with dexamethasone 20mg (adults) 1hr prior to 1st dose of each cycle, or dexamethasone 5mg/m2 to max 20mg (pediatrics) prior to 1st dose in the 1st cycle, plus prior to a step dose, and when restarting infusion after interruption (≥4hrs) for both adults and pediatrics. Treat up to 9 cycles (2 cycles for induction, followed by 3 cycles for consolidation, and up to 4 additional cycles of continued therapy). One single cycle = 28 days of continuous IV infusion followed by a 14-day treatment-free interval (during Cycles 1–5) and 56-day treatment-free interval (during Cycles 6–9). Hospitalization recommended for first 9 days of Cycle 1 and first 2 days of Cycle 2. <45kg (Cycle 1): 5mcg/m2/day (max 9mcg/day) on Days 1–7 and 15mcg/m2/day (max 28mcg/day) on Days 8–28; (Cycles 2–9): 15mcg/m2/day (max 28mcg/day) on Days 1–28. ≥45kg (Cycle 1): 9mcg/day on Days 1–7 and 28mcg/day on Days 8–28; (Cycles 2–9): 28mcg/day on Days 1–28. Dose adjustments, using 24-hr, 48-hr, or 7-day infusion of Blincyto: see full labeling.

Boxed Warning:

Cytokine release syndrome. Neurological toxicities.

BLINCYTO Warnings/Precautions:

Monitor for cytokine release syndrome, neurological toxicities (eg, seizures, loss of consciousness), tumor lysis syndrome; interrupt or discontinue as recommended (see full labeling). Monitor for infections; give antibiotic prophylaxis as appropriate. Obtain lab tests (including WBC, ANC) during infusion; interrupt if prolonged neutropenia occurs. Monitor ALT, AST, GGT, and total bilirubin prior to and during treatment; interrupt if transaminases rise >5×ULN or if bilirubin rises >3×ULN. Evaluate if signs/symptoms of pancreatitis develop; interrupt or discontinue as appropriate. Risk of leukoencephalopathy, esp. in those with prior treatment with cranial irradiation and antileukemic chemotherapy (including high-dose methotrexate or intrathecal cytarabine). Elderly. Neonates/infants: risk of gasping syndrome (due to benzyl alcohol preservative). Pregnancy: exclude status prior to initiation. Advise females of reproductive potential to use effective contraception during and for ≥48hrs after the last dose. Nursing mothers: not recommended (during and for ≥48hrs after the last dose).

BLINCYTO Classification:

Bispecific CD19-directed CD3 T-cell engager.

BLINCYTO Interactions:

Concomitant live vaccines: not recommended (for ≥2 weeks prior to initiation, during treatment, and until immune recovery after last cycle). Caution with concomitant CYP450 substrates esp. drugs with narrow therapeutic index (eg, warfarin, cyclosporine); monitor and adjust dose as needed.

Adverse Reactions:

Infections, pyrexia, headache, infusion-related reactions, anemia, febrile neutropenia, thrombocytopenia, neutropenia; tremor, encephalopathy, aphasia, sepsis, overdose, septic shock.

Metabolism:

The metabolic pathway of blinatumomab has not been characterized. Like other protein therapeutics, Blincyto is expected to be degraded into small peptides and amino acids via catabolic pathways.

Drug Elimination:

The estimated mean (SD) systemic clearance with continuous intravenous infusion in patients receiving blinatumomab in clinical studies was 3.11 (2.98) L/hour. The mean (SD) half-life was 2.10 (1.41) hours. Negligible amounts of blinatumomab were excreted in the urine at the tested clinical doses. 

REMS:

YES

Generic Drug Availability:

NO

How Supplied:

Pack—1 (single-use vial + IV solution stabilizer)