Elzonris

ELZONRIS should be administered under the supervision of a physician experienced in the use of anti-cancer agents. Appropriate resuscitation equipment should be available. Posology The recommended dose is 12 mcg/kg tagraxofusp administered as an intravenous infusion over 15 minutes, once daily, on days 1-5 of a 21-day cycle.

The dosing period may be extended for dose delays up to day 10 of the cycle. 4). First treatment cycle The first cycle of ELZONRIS should be administered in the in-patient setting. 4) until at least 24 hours after the last infusion. Subsequent treatment cycles 3 ELZONRIS can be administered in the in-patient setting or in a suitable out-patient ambulatory care setting that is equipped for intensive monitoring of patients with haematopoietic malignancies undergoing treatment.

g. g. 4). Dose adjustments Vital signs should be monitored and albumin, transaminases, and creatinine checked prior to preparing each dose of ELZONRIS. See Table 1 for recommended dose modifications and Table 2 for capillary leak syndrome (CLS) management guidelines.

Vital signs should be monitored frequently during dosing. 5 times the upper limit of normal. 8 mg/dL (159 micromol/L) or creatinine clearance ≥ 60 mL/minute. Systolic blood pressure Systolic blood pressure ≥ 160 mmHg or ≤ 80 mmHg Withhold treatment until systolic blood pressure is < 160 mmHg or > 80 mmHg.

Heart rate Heart rate ≥ 130 bpm or ≤ 40 bpm Withhold treatment until heart rate is < 130 bpm or > 40 bpm. Body temperature Body temperature ≥ 38 °C Withhold treatment until body temperature is < 38 °C. Hypersensitivity reactions Mild or moderate Withhold treatment until resolution of any mild or moderate hypersensitivity reaction.

Resume ELZONRIS at the same infusion rate. 5 g/dL AND not reduced by Hold dosing until the relevant CLS sign/symptom 4 1 If ELZONRIS dose is held: - ELZONRIS administration may resume in the same cycle if all CLS signs/symptoms have resolved and the patient did not require measures to treat haemodynamic instability.

, required administration of intravenous fluids and/or vasopressors to treat hypotension) (even if resolved). - Administration may only resume in the next cycle if all CLS signs/symptoms have resolved, and the patient is haemodynamically stable.

2). 2). 2). Generally, safety was similar between elderly patients (≥ 65 years of age) and patients less than 65 years of age treated with ELZONRIS. e. 5 kg greater than the previous day’s pre-dose weight). 5 g/dL. Administer 1 mg/kg of methylprednisolone (or an equivalent) per day, until resolution of CLS sign/symptom or as indicated clinically.

4) which was reported in 18% of patients with a median time to onset of CLS of 6 days. Adverse reactions occurring in ≥ 20% of patients treated with ELZONRIS were hypoalbuminemia, increased transaminases, thrombocytopenia, nausea, fatigue and pyrexia.

Adverse reactions grade 3 and above according to the Common Terminology Criteria for Adverse events (CTCAE) and occurring in > 5% of patients were increased transaminases, thrombocytopenia and anaemia. Tabulated list of adverse reactions The adverse reaction frequency is listed by MedDRA System Organ Class (SOC) at the preferred term level.

Frequencies of occurrence of adverse reactions are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1000 to < 1/100). The adverse reactions described in this section were identified in clinical studies of patients with haematologic malignancies (N=176), including 89 patients with BPDCN.

In these studies, ELZONRIS was administered as monotherapy at doses of 7 mcg/kg (12/176, 7%), 9 mcg/kg (9/176, 5%) and 12 mcg/kg (155/176, 88%). Incidence and severity of adverse reaction in patients with BPDCN were similar to those of the entire studied population.

8 Table 3: Tabulated list of adverse reactions by MedDRA System Organ Class MedDRA System Organ Class Frequency of all CTCAE grades Frequency of CTCAE grade 3 and above Infections and infestations Common Cellulitis Uncommon Pneumonia Urinary tract infection Gingivitis None Blood and lymphatic system disorders Very Common Thrombocytopenia Anaemia Common Febrile neutropenia Neutropenia Leukopenia Leukocytosis Lymphopenia Very Common Thrombocytopenia Common Febrile neutropenia Anaemia Neutropenia Leukopenia Lymphopenia Uncommon Leukocytosis Immune system disorders Common Cytokine release syndrome Uncommon Cytokine release syndrome Metabolism and nutrition disorders Very Common Hypoalbuminemia Common Decreased appetite Tumour lysis syndrome Hyperglycaemia Hyperuricaemia Hypocalcaemia Hypomagnesaemia Hyponatraemia Hypokalaemia Hyperkalaemia Hyperphosphataemia Uncommon Hypophosphataemia Lactic acidosis Acidosis Common Tumour lysis syndrome Hyperglycaemia Hypoalbuminemia Hyponatraemia Uncommon Hyperuricaemia Hypocalcaemia Hypokalaemia Lactic acidosis Acidosis Psychiatric disorders Common Confusional state Uncommon Anxiety Depression Insomnia Mental status changes None Nervous system disorders Common Syncope Headache Dizziness Uncommon Encephalopathy Metabolic encephalopathy Cerebrovascular accident Facial paralysis Dysgeusia Multiple sclerosis relapse Somnolence Paraesthesia Parosmia Peripheral motor neuropathy Peripheral sensory neuropathy Common Syncope Uncommon Cerebrovascular accident Metabolic encephalopathy Eye Disorders Common None 9 MedDRA System Organ Class Frequency of all CTCAE grades Frequency of CTCAE grade 3 and above Vision blurred Uncommon Conjunctival haemorrhage Ocular hyperaemia Vitreous floaters Cardiac Disorders Common Pericardial effusion Tachycardia Sinus tachycardia Uncommon Ventricular fibrillation Supraventricular extrasystoles Atrial fibrillation Bradycardia Myocardial infarction Uncommon Ventricular fibrillation Pericardial effusion Sinus tachycardia Myocardial infarction Vascular disorders Very Common Capillary leak syndrome Hypotensiona Common Flushing Uncommon Hypertension Haematoma Common Capillary leak syndrome Hypotension Respiratory, thoracic and mediastinal disorders Common Hypoxia Pulmonary oedema Dyspnoea Epistaxis Pleural effusion Cough Uncommon Respiratory failure Wheezing Oropharyngeal pain Tachypnoea Common Hypoxia Pulmonary oedema Uncommon Respiratory failure Dyspnoea Gastrointestinal Disorders Very Common Nausea Vomiting Common Dysphagia Diarrhoea Stomatitis Dyspepsia Dry mouth Constipation Uncommon Abdominal distension Abdominal pain Gingival bleeding Tongue blistering Tongue haematoma Uncommon Nausea Hepatobiliary disorders Common Hyperbilirubinemia None Skin and subcutaneous tissue disorders Common Pruritus Rashb Hyperhidrosis Petechiae Uncommon Angioedema Uncommon Angioedema Rash 10 MedDRA System Organ Class Frequency of all CTCAE grades Frequency of CTCAE grade 3 and above Swelling face Palmar-plantar erythrodysesthesia syndrome Urticaria Alopecia Pain of skin Stasis dermatitis Cold sweat Dry skin Musculoskeletal and connective tissue disorders Common Back pain Bone pain Myalgia Arthralgia Pain in extremity Muscular weakness Uncommon Musculoskeletal pain Coccydynia Muscle spasms Rhabdomyolysis Uncommon Back pain Arthralgia Rhabdomyolysis Renal and urinary disorders Common Acute kidney injury Uncommon Renal failure Urinary retention Urinary tract pain Pollakiuria Proteinuria Uncommon Acute kidney injury General disorders and administration site conditions Very Common Pyrexia Chills Fatiguec Oedema peripherald Common Influenza-like illness Chest pain Pain Malaise Uncommon Drug intolerance Hypothermia Systemic inflammatory response syndrome Common Fatigue Uncommon Pyrexia Chills Oedema peripheral Drug intolerance Investigations Very Common Transaminases increasede Weight increased Common Electrocardiogram QT prolonged Blood alkaline phosphatase increased Blood creatinine increased Blood lactate dehydrogenase increased Blood creatine phosphokinase increased Activated partial thromboplastin time prolonged International normalised ratio increased Uncommon Blood fibrinogen decreased Bacterial test positive Weight decreased Very Common Transaminases increased Uncommon Electrocardiogram QT prolonged Blood lactate dehydrogenase increased Bacterial test positive 11 MedDRA System Organ Class Frequency of all CTCAE grades Frequency of CTCAE grade 3 and above Injury, poisoning and procedural complications Common Infusion related reaction Contusion Uncommon Infusion related reaction a Includes procedural hypotension, orthostatic hypotension b Includes rash pustular, […]

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. Capillary leak syndrome Capillary leak syndrome (CLS), including life-threatening and fatal cases have been reported with most events occuring during the first five days of the first cycle of treatment.

The most frequent signs and symptoms of CLS included weight increased, hypoalbuminemia and hypotension. The incidence of weight increased, hypoalbuminemia, hypotension, and blood alkaline phosphatase increased are all higher among patients who experienced CLS compared to patients that did not experience CLS.

8). 2 g/dL. During treatment, regularly monitor serum albumin levels prior to the initiation of each dose, or more often as clinically indicated. Additionally, assess patients for other signs/symptoms of CLS including weight gain, new onset or worsening oedema, including pulmonary oedema, and hypotension including haemodynamic instability (see Table 2).

Patients should be made aware of identifying CLS symptoms and when to seek immediate medical attention. 2). Hypersensitivity reactions Severe hypersensitivity reactions have been reported with ELZONRIS. 8). Monitor patients for hypersensitivity reactions during treatment.

2). 8). The majority of events were reported in cycle 1 and cycle 2 of treatment, were not dose-limiting and did not recur in subsequent cycles. Patients should be routinely monitored and treated as clinically indicated. 8). Identify TLS based on clinical presentation and symptoms, including acute renal failure, hyperkalaemia, hypocalcaemia, hyperuricaemia, or hyperphosphataemia from tumour lysis.

Patients considered at high risk for TLS due to high tumour burden should be managed as clinically indicated, including correction of electrolyte abnormalities, monitoring of renal function and fluid balance, and administration of supportive care.

1.