The safety and efficacy of BLINCYTO in pediatric patients less than 1 month of age have not been established for any indication [see Indications and Usage (1)].

Minimal Residual Disease (MRD)-Positive B-cell Precursor ALL

The safety and efficacy of BLINCYTO for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% have been established in pediatric patients one month and older. Use of BLINCYTO is supported by evidence from two randomized, controlled trials (Study AALL1331, NCT02101853 and Study 20120215, NCT02393859) [see Clinical Studies (14.3)] in pediatric patients with first relapsed B-cell precursor ALL. Both studies included pediatric patients with MRD-positive B-cell precursor ALL. The studies included pediatric patients treated with BLINCYTO in the following age groups: 6 infants (1 month up to less than 2 years), 165 children (2 years up to less than 12 years), and 70 adolescents (12 years to less than 17 years). In general, the adverse reactions in BLINCYTO-treated pediatric patients were similar in type to those seen in adult patients with MRD-positive ALL [see Adverse Reactions (6.1)], and no differences in safety were observed between the different pediatric age subgroups.

Relapsed or Refractory B-cell Precursor ALL

The safety and efficacy of BLINCYTO have been established in pediatric patients one month and older with relapsed or refractory B-cell precursor ALL. Use of BLINCYTO is supported by a single-arm trial in pediatric patients with relapsed or refractory B-cell precursor ALL. This study included pediatric patients in the following age groups: 10 infants (1 month up to less than 2 years), 40 children (2 years up to less than 12 years), and 20 adolescents (12 years to less than 18 years). No differences in efficacy were observed between the different age subgroups [see Clinical Studies (14.2)].

In general, the adverse reactions in BLINCYTO-treated pediatric patients with relapsed or refractory ALL were similar in type to those seen in adult patients with relapsed or refractory B-cell precursor ALL [see Adverse Reactions (6.1)]. Adverse reactions that were observed more frequently (≥ 10% difference) in the pediatric population compared to the adult population were pyrexia (80% vs. 61%), hypertension (26% vs. 8%), anemia (41% vs. 24%), infusion-related reaction (49% vs. 34%), thrombocytopenia (34% vs. 21%), leukopenia (24% vs. 11%), and weight increased (17% vs. 6%).

In pediatric patients less than 2 years old (infants) with relapsed or refractory ALL, the incidence of neurologic toxicities was not significantly different than for the other age groups, but its manifestations were different; the only event terms reported were agitation, headache, insomnia, somnolence, and irritability. Infants also had an increased incidence of hypokalemia (50%) compared to other pediatric age cohorts (15-20%) or adults (17%).

B-cell Precursor ALL in the Consolidation Phase

The safety and efficacy of BLINCYTO for the treatment of Philadelphia-chromosome negative B-cell precursor ALL in the consolidation phase have been established in pediatric patients one month and older. Use of BLINCYTO for this indication is supported by extrapolation from a randomized controlled study in adults (Study E1910, NCT02003222) and evidence from two randomized, controlled studies in pediatric patients (Study 20120215 and Study AALL1331) [see Adverse Reactions (6.1), Use in Specific Populations (8.4), Clinical Pharmacology (12.3), and Clinical Studies (14.3)].

Benzyl Alcohol Toxicity in Neonates

Serious and fatal adverse reactions, including "gasping syndrome," can occur in very low birth weight (VLBW) neonates born weighing less than 1500 g, and early preterm neonates (infants born less than 34 weeks gestational age) treated with benzyl alcohol-preserved drugs intravenously. The "gasping syndrome" is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. In these cases, benzyl alcohol dosages of 99 to 234 mg/kg/day produced high concentrations of benzyl alcohol and its metabolite in the blood and urine (blood concentration of benzyl alcohol were 0.61 to 1.378 mmol/L). Additional adverse reactions included gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. The minimum amount of benzyl alcohol at which serious adverse reactions may occur in neonates is not known [see Warnings and Precautions (5.12)].

Use the preservative-free formulations of BLINCYTO where possible in neonates. When prescribing BLINCYTO (with preservative) in neonatal patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO (with preservative). The BLINCYTO 7-Day bag (with preservative) contains 7.4 mg of benzyl alcohol per mL [see Warnings and Precautions (5.12)].

Benzyl alcohol administration may contribute to metabolic acidosis in pediatric patients, particularly those with immaturity of the metabolic pathway for alcohol, or those with underlying conditions or receiving concomitant medications that could predispose to acid base imbalance. Monitor these patients during use of BLINCYTO (with preservative) for new or worsening metabolic acidosis.