Blincyto

Treatment should be initiated under the direction of and supervised by physicians experienced in the treatment of haematological malignancies. Patients treated with BLINCYTO should be given the Educational Brochure for Patients and Caregivers and the Patient Card.

For the treatment of relapsed or refractory B-cell precursor ALL, hospitalisation is recommended for initiation at a minimum for the first 9 days of the first cycle and the first 2 days of the second cycle. For the treatment of Philadelphia chromosome-negative MRD positive B-cell precursor ALL, hospitalisation is recommended at a minimum for the first 3 days of the first cycle and the first 2 days of subsequent cycles.

For the treatment of B-cell precursor ALL in the consolidation phase, hospitalisation is recommended for the first 3 days of the first cycle and the first 2 days of the second cycle. 4), hospitalisation is recommended at a minimum for the first 14 days of the first cycle.

In the second cycle, hospitalisation is recommended at a minimum for 2 days, and clinical judgement should be based on tolerance to BLINCYTO in the first cycle. Caution should be exercised as cases of late occurrence of first neurological events have been observed.

g. if treatment is interrupted for 4 or more hours), supervision by a healthcare professional or hospitalisation is recommended. Posology Relapsed or refractory B-cell precursor ALL Patients with relapsed or refractory B-cell precursor ALL, may receive 2 cycles of treatment.

A single cycle of treatment is 28 days (4 weeks) of continuous infusion. Each cycle of treatment is separated by a 14-day (2 weeks) treatment-free interval. Patients who have achieved complete remission (CR/CRh*) after 2 treatment cycles may receive up to 3 additional cycles of BLINCYTO consolidation treatment, based on an individual benefits-risks assessment.

Recommended daily dose is by body weight (see table 1). Patients greater than or equal to 45 kg receive a fixed-dose and for patients less than 45 kg, the dose is calculated using the patient’s body surface area (BSA). Table 1. BLINCYTO recommended dosage for relapsed or refractory B-cell precursor ALL Body weight Cycle 1 Subsequent cycles Days 1-7 Days 8-28 Days 29-42 Days 1-28 Days 29-42 Greater than or equal to 45 kg (fixed-dose) 9 mcg/day via continuous infusion 28 mcg/day via continuous infusion 14-day treatment- free interval 28 mcg/day via continuous infusion 14-day treatment-free interval Less than 45 kg (BSA-based dose) 5 mcg/m2/day via continuous infusion (not to exceed 9 mcg/day) 15 mcg/m2/day via continuous infusion (not to exceed 28 mcg/day) 15 mcg/m2/day via continuous infusion (not to exceed 28 mcg/day) 4 Premedication and additional medication recommendations In adult patients, dexamethasone 20 mg intravenous should be administered 1 hour prior to initiation of each cycle of BLINCYTO therapy.

Summary of the safety profile The adverse reactions described in this section were identified in clinical studies of patients with B-cell precursor ALL (N = 1 045). 8%). 6%). Tabulated list of adverse reactions Adverse reactions are presented below by system organ class and frequency category.

Frequency categories were determined from the crude incidence rate reported for each adverse reaction in clinical studies of patients with B-cell precursor ALL (N = 1 045). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

MedDRA system organ class Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1 000 to < 1/100) Infections and infestations Bacterial infectionsa, b Viral infectionsa, b Infections - pathogen unspecifieda, b Sepsis Pneumonia Fungal infectionsa, b Blood and lymphatic system disorders Febrile neutropenia Anaemia1 Neutropenia2 Thrombocytopenia3 Leukopenia4 Leukocytosis5 Lymphopenia6 Lymphadenopathy Haemophagocytic lymphohistiocytosis (HLH) Immune system disorders Cytokine release syndromea Hypersensitivity Cytokine storm Metabolism and nutrition disorders Tumour lysis syndrome Psychiatric disordersa Insomnia18 Confusional state18 Disorientation18 Nervous system disordersa Headache18 Tremor18 Encephalopathy18 Aphasia18 Paraesthesia18 Seizure18 Cognitive disorder18 Memory impairment Dizziness18 Somnolence18 Hypoaesthesia18 Cranial nerve disorderb Ataxia18 Immune effector cell- associated neurotoxicity syndrome (ICANS) Speech disorder18 Cardiac disorders Tachycardia7 Vascular disorders Hypotension8 Hypertension9 Flushing Capillary leak syndrome Respiratory, thoracic and mediastinal disorders Cough Dyspnoea Productive cough Respiratory failure Wheezing Dyspnoea exertional Acute respiratory failure Gastrointestinal disorders Nausea Diarrhoea Vomiting Constipation Abdominal pain Pancreatitisa Hepatobiliary disorders Hyperbilirubinaemiaa, 10 18 MedDRA system organ class Very common (≥ 1/10) Common (≥ 1/100 to < 1/10) Uncommon (≥ 1/1 000 to < 1/100) Skin and subcutaneous tissue disorders Rash11 Musculoskeletal and connective tissue disorders Back pain Pain in extremity Bone pain General disorders and administration site conditions Pyrexia12 Chills Oedema13 Chest pain14 Pain Investigations Hepatic enzyme increaseda, 15 Decreased immunoglobulins16 Weight increased Blood alkaline phosphatase increased Injury, poisoning and procedural complications Infusion-related reactions17 a Additional information is provided in “Description of selected adverse reactions”.

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Neurologic events including ICANS Neurologic events including events with a fatal outcome have been observed.

0) or higher (severe or life-threatening) neurologic events including ICANS following initiation of blinatumomab administration included encephalopathy, seizures, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders.

Among patients that experienced a neurologic event, the median time to the first event was within the first 2 weeks of treatment and the majority of events resolved after treatment interruption and infrequently led to BLINCYTO treatment discontinuation.

Elderly patients may be more susceptible to serious neurologic events such as cognitive disorder, encephalopathy, and confusion. Patients with a medical history of neurologic signs and symptoms (such as dizziness, hypoaesthesia, hyporeflexia, tremor, dysaesthesia, paraesthesia and memory impairment) demonstrated a higher rate of neurologic events (such as tremor, dizziness, confusional state, encephalopathy and ataxia).

Among these patients, the median time to the first neurologic event was within the first cycle of treatment. g. epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome and psychosis) as they were excluded from clinical studies.

There is a possibility of a higher risk of neurologic events in this population. The potential benefits of treatment should be carefully weighed against the risk of neurologic events and heightened caution should be exercised when administering BLINCYTO to these patients.

There is limited experience with blinatumomab in patients with documented active ALL in the CNS or cerebrospinal fluid (CSF). However, patients have been treated with blinatumomab in clinical studies after clearance of CSF blasts with CNS directed therapy (such as intrathecal chemotherapy).

1. 6).