Acute Lymphoblastic Leukaemia in Adult Patients MedDRA system class Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1000 to < 1/100) Infections and infestations Fungal infections Bacterial infections Viral infections Other pathogen infections Sepsis Pneumonia Blood and lymphatic system disorders Febrile neutropenia Neutropenia Thrombocytopenia Anaemia Leukopenia Lymphopenia Leukocytosis histiocytosis Immune system disorders Cytokine release syndrome Hypersensitivity Cytokine storm Metabolism and nutrition disorders Hypokalaemia Hyperglycaemia Tumour lysis syndrome Hypomagnesaemia Hypoalbuminemia Psychiatric disorders Insomnia Confusion Disorientation Nervous system disorders Tremor Headache Dizziness Encephalopathy Convulsion Aphasia Paraesthesia Speech disorder Memory impairment Cognitive disorder Cardiac disorders Tachycardia Vascular disorders Hypotension Capillary leak syndrome Respiratory, thoracic and mediastinal disorders
MedDRA system organ class Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1000 to < 1/100) Gastrointestinal disorders Vomiting Abdominal pain Diarrhoea Constipation Nausea Hepatobiliary disorders Increased liver enzymes (including increased alanine aminotransferase, increased aspartate aminotransferase and gamma-glutamyl transferase) Increased bilirubin Skin and subcutaneous tissue disorders Rash Musculoskeletal and connective tissue disorders Back pain Pain in extremity Arthralgia Bone pain General disorders and administration site conditions Pyrexia Peripheral oedema Fatigue Chills Chest pain Oedema Investigations Increased weight Decreased immunoglobulins Injury, poisoning and procedural complications Infusion-related reactions and associated symptoms including wheezing, flushing, face swelling, dyspnoea, hypotension, and hypertension
1.1 – 1.19 2.1 mL 1 – 1.09 1.9 mL 0.9 – 0.99 1.7 mL 0.8 – 0.89 1.5 mL 0.7 – 0.79 1.3 mL 0.6 – 0.69 1.2 mL 0.5 – 0.59 0.98 mL 0.4 – 0.49 0.80 mL Table 6. For Patients Weighing Less Than 45 kg: Volumes of Reconstituted Blincyto to add to IV Bag for 15 micrograms/m2/day Dose Dose Infusion Duration Infusion Rate BSA (m2) Reconstituted BLINCYTO 15 24 hours 10 mL/hour 1.5 – 1.59 2.1 mL 1.4 – 1.49 2 mL 1.3 – 1.39 1.8 mL 1.2 – 1.29 1.7 mL 1.1 – 1.19 1.5 mL 1 – 1.09 1.4 mL 0.9 – 0.99 1.3 mL 0.8 – 0.89 1.1 mL 0.7 – 0.79 1.01 mL 0.6 – 0.69 0.87 mL 0.5 – 0.59 0.74 mL 0.4 – 0.49 0.6 mL 48 hours 5 mL/hour 1.5 – 1.59 4.2 mLa 1.4 – 1.49 3.9 mLa
1.3 – 1.39 3.6 mLa 1.2 – 1.29 3.4 mLa 1.1 – 1.19 3.1 mLa 1 – 1.09 2.8 mL 0.9 – 0.99 2.6 mL 0.8 – 0.89 2.3 mL 0.7 – 0.79 2 mL 0.6 – 0.69 1.7 mL 0.5 – 0.59 1.5 mL 0.4 – 0.49 1.2 mL Dose Infusion Duration Infusion Rate BSA (m2) Reconstituted BLINCYTO 72 3.3 mL/hour 1.5 – 1.59 6.3 mLb 1.4 – 1.49 5.9 mLb 1.3 – 1.39 5.4 mLc 1.2 – 1.29 5.0 mLc 1.1 – 1.19 4.6 mLc 1 – 1.09 4.2 mLc 0.9 – 0.99 3.8 mLc 0.8 – 0.89 3.4 mLc 0.7 – 0.79 3 mLc 0.6 – 0.69 2.6 mL 0.5 – 0.59 2.2 mL 0.4 – 0.49 1.8 mL
48 hours 2 4.7 mL 72 hours 3 7 mL 96 hours 4 9.3 mL *Extractable amount per vial is 35 micrograms in a volume of 2.8 mL reconstituted solution. Table 8. For Patients Weighing Less Than 45 kg: Volume of Blincyto required for 250 mL cassette for 5 mcg/m2/day Dose Dose Cassette Duration Expected Number of Blincyto vials required* BSA (m2) Volume of Reconstituted BLINCYTO 5 mcg/m2/day 24 hours 1 1.5 – 1.59 0.65 1 1.4 – 1.49 0.6 1 1.3 – 1.39 0.56 1 1.2 – 1.29 0.52 1 1.1 – 1.19 0.48 1 1 – 1.09 0.44 1 0.9 – 0.99 0.39 1 0.8 – 0.89 0.35 1 0.7 – 0.79 0.31 1 0.6 – 0.69 0.27 1 0.5 – 0.59 0.23 1 0.4 – 0.49 0.19 48 1 1.5 – 1.59 1.3 1 1.4 – 1.49 1.2 1 1.3 – 1.39 1.1 1 1.2 – 1.29 1 1 1.1 – 1.19 0.95
1 1 – 1.09 0.87 1 0.9 – 0.99 0.79 1 0.8 – 0.89 0.7 1 0.7 – 0.79 0.62 1 0.6 – 0.69 0.54 1 0.5 – 0.59 0.45 1 0.4 – 0.49 0.37 72 hours 1 1.5 – 1.59 1.9 Dose Cassette Duration Expected Number of Blincyto vials required* BSA (m2) Volume of Reconstituted BLINCYTO 1 1.4 – 1.49 1.8 1 1.3 – 1.39 1.7 1 1.2 – 1.29 1.6 1 1.1 – 1.19 1.4 1 1 – 1.09 1.3 1 0.9 – 0.99 1.2 1 0.8 – 0.89 1.1 1 0.7 – 0.79 0.93 1 0.6 – 0.69 0.81 1 0.5 – 0.59 0.68 1 0.4 – 0.49 0.56 96 hours 1 1.5 – 1.59 2.6 1 1.4 – 1.49 2.4
1 1.3 – 1.39 2.2 1 1.2 – 1.29 2.1 1 1.1 – 1.19 1.9 1 1 – 1.09 1.7 1 0.9 – 0.99 1.6 1 0.8 – 0.89 1.4 1 0.7 – 0.79 1.2 1 0.6 – 0.69 1.1 1 0.5 – 0.59 0.91 1 0.4 – 0.49 0.74
Table 9. For Patients Weighing Less Than 45 kg: Volume of Blincyto required for 250 mL cassette for 15 mcg/m2/day Dose Dose Cassette Duration Expected Number of Blincyto required* BSA (m2) Volume of Reconstituted BLINCYTO 15 mcg/m2/day 24 1 1.5 – 1.59 1.9 1 1.4 – 1.49 1.8 1 1.3 – 1.39 1.7 1 1.2 – 1.29 1.6 1 1.1 – 1.19 1.4 1 1 – 1.09 1.3 1 0.9 – 0.99 1.2 1 0.8 – 0.89 1.1 1 0.7 – 0.79 0.93 1 0.6 – 0.69 0.81 1 0.5 – 0.59 0.68 1 0.4 – 0.49 0.56 48 hours 2 1.5 – 1.59 3.9 2 1.4 – 1.49 3.6 2 1.3 – 1.39 3.4 2 1.2 – 1.29 3.1 2 1.1 – 1.19 2.9 1 1 – 1.09 2.6 1 0.9 – 0.99 2.4 1 0.8 – 0.89 2.1
2 1 – 1.09 5.2 2 0.9 – 0.99 4.7 2 0.8 – 0.89 4.2 2 0.7 – 0.79 3.7 2 0.6 – 0.69 3.2 1 0.5 – 0.59 2.7 1 0.4 – 0.49 2.2