Breyanzi

• Frequency of monitoring after the first week should be carried out at the physician’s discretion and should be continued for at least 2 weeks after infusion. • Patients should be instructed to remain within proximity of a qualified treatment centre for at least 2 weeks following infusion.

Special populations Patients with human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infection There is no clinical experience in patients with active HIV, HBV or HCV infection. Screening for HIV, active HBV and active HCV must be performed before collection of cells for manufacturing.

4). Renal impairment There is no clinical experience in patients with severe renal impairment (creatinine clearance ≤ 30 mL/min). Elderly No dose adjustment is required in patients over 65 years of age. 5 Paediatric population The safety and efficacy of Breyanzi in children and adolescents below 18 years of age have not yet been established.

Method of administration Breyanzi is for intravenous use only. Preparation of Breyanzi Before thawing the vials, it must be confirmed that the patient’s identity matches the unique patient identifiers on the shipper, external carton and the release for infusion certificate (RfIC).

4). The company must be contacted immediately if there are any discrepancies between the labels and the patient identifiers. Administration • Do NOT use a leukodepleting filter. • Ensure tocilizumab or suitable alternatives, in the exceptional case where tocilizumab is not available due to a shortage that is listed in the European Medicines Agency shortage catalogue, and emergency equipment are available prior to infusion and during the recovery period.

• Confirm the patient’s identity matches the patient identifiers on the syringe label supplied on the respective release for infusion certificate (RfIC). • Once Breyanzi components have been drawn into syringes, proceed with administration as soon as possible.

The total time from removal from frozen storage to patient administration should not exceed 2 hours. 6.

The most common adverse reactions of any grade were neutropenia (68%), CRS (58%), anaemia (40%), headache (29%), thrombocytopenia (29%) and constipation (21%). The most common serious adverse reactions were CRS (9%), aphasia (4%), febrile neutropenia (3%), pyrexia (2%) and tremor (2%).

The most common Grade 3 or higher adverse reactions included neutropenia (61%), leukopenia (12%), lymphopenia (12%), thrombocytopenia (12%) and anaemia (10%). MCL The adverse reactions described in this section were characterised in 88 patients infused with Breyanzi from study TRANSCEND-MCL Cohort [017001].

The most common adverse reactions of any grade were CRS (61%), neutropenia (59%), anaemia (44%), fatigue (35%), thrombocytopenia (30%), and headache (23%). The most common serious adverse reactions were CRS (24%), confusional state (6%), pyrexia (3%), mental status changes (2%), encephalopathy (2%), upper respiratory tract infection (2%), and pleural effusion (2%).

The most common Grade 3 or higher adverse reactions included neutropenia (56%), anaemia (38%), thrombocytopenia (25%), hypophosphataemia (9%), and leukopenia (7%). 15 Tabulated list of adverse reactions The frequencies of adverse reactions are based on pooled data from 7 studies (TRANSCEND [017001], including LBCL and MCL Cohorts, TRANSCEND WORLD [JCAR017-BCM-001, Cohort 1, 2, 3 and 7], PLATFORM [JCAR017-BCM-002], OUTREACH [017007], TRANSFORM [BCM-003], PILOT [017006] and TRANSCEND-FL (JCAR017-FOL-001), in 779 adult patients and from post-marketing reports who received a dose of lisocabtagene maraleucel.

The adverse reaction frequencies from clinical studies are based on all-cause adverse event frequencies, where a proportion of the events for an adverse reaction may have other causes. Adverse reactions reported are presented below.

These reactions are presented by MedDRA system organ class and by frequency. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) and not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness.

Table 3:

Adverse drug reactions identified with Breyanzi System Organ Class (SOC) Frequency Adverse reaction Infections and infestationsa Very common Infections - pathogen unspecified Common Bacterial infectious disorders Viral infectious disorders Fungal infectious disorders Neoplasms benign, malignant and unspecified (including cysts and polyps) Uncommon Secondary malignancy of T-cell origin Blood and lymphatic system disorders Very common Neutropenia Anaemia Thrombocytopenia Leukopenia Lymphopenia Common Febrile neutropenia Hypofibrinogenaemiaw Uncommon Pancytopenia Immune system disorders Very common Cytokine release syndrome Common Hypogammaglobulinaemiav Uncommon Haemophagocytic lymphohistiocytosis Metabolism and nutrition disorders Common Hypophosphataemia Uncommon Tumour lysis syndrome Psychiatric disorders Very common Insomnia Common Deliriumb Anxiety 16 System Organ Class (SOC) Frequency Adverse reaction Nervous system disorders Very common Headachec Encephalopathyd Dizzinesse Tremorf Common Aphasiag Peripheral neuropathyh Visual disturbancei Ataxiaj Taste disorderk Cerebellar syndromel Uncommon Cerebrovascular disorderm Seizuren Paresiso Brain oedema Not known Immune effector cell-associated neurotoxicity syndrome* Cardiac disorders Very common Tachycardia Common Arrhythmiap Uncommon Cardiomyopathy Vascular disorders Very common Hypotension Common Hypertension Thrombosisq Respiratory, thoracic and mediastinal disorders Very common Cough Common Dyspnoear Pleural effusion Hypoxia Uncommon Pulmonary oedema Gastrointestinal disorders Very common Nausea Diarrhoea Constipation Abdominal pain Vomiting Common Gastrointestinal […]

For patients who received Breyanzi for FL, the median time to onset was 6 days (range: 1 to 17 days). For patients who received Breyanzi for MCL, the median time to onset was 4 days (range: 1 to 10 days). 8). In clinical studies, high tumour burden prior to Breyanzi infusion was associated with a higher incidence of CRS.

8). Monitoring and management of CRS CRS should be identified based on clinical presentation. Patients should be evaluated for and treated for other causes of fever, hypoxia, and hypotension. At least one dose of tocilizumab must be available per patient on site prior to infusion of Breyanzi.

The treatment centre should have access to an additional dose of tocilizumab within 8 hours of each previous dose. In the exceptional case where tocilizumab is not available due to a shortage that is listed in the European Medicines Agency shortage catalogue, the treatment centre must have access to suitable alternative measures instead of tocilizumab to treat CRS.

Patients should be monitored 2-3 times during the first week following Breyanzi infusion at the qualified treatment centre for signs and symptoms of CRS. Frequency of monitoring after the first week should be carried out at the physician’s discretion and should be continued for at least 2 weeks after infusion.

Patients and caregivers should be informed about the potential late onset of CRS and instructed to seek immediate medical attention if patients experience any signs or symptoms of CRS. At the first sign of CRS, treatment with supportive care, tocilizumab or tocilizumab and corticosteroids should be instituted as indicated in Table 1.

2). 7 Patients who experience CRS should be closely monitored for cardiac and organ functioning until resolution of symptoms. For severe or life-threatening CRS, intensive care unit level monitoring and supportive therapy should be considered.

Evaluation for haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS) should be considered in patients with severe or unresponsive CRS. Treatment of HLH/MAS should be administered per institutional guidelines. If concurrent neurologic toxicity is suspected during CRS, administer: • Corticosteroids according to the more aggressive intervention based on the CRS and neurologic toxicity grades in Tables 1 and 2 • Tocilizumab according to the CRS grade in Table 1 • Anti-seizure medication according to the neurologic toxicity grade in Table 2.

Table 1:

CRS grading and management guidance CRS gradea Tocilizumab Corticosteroidsb Grade 1 Fever If 72 hours or more after infusion, treat symptomatically. If less than 72 hours after infusion, consider tocilizumab 8 mg/kg IV over 1 hour (not to exceed 800 mg).

If 72 hours or more after infusion, treat symptomatically. If less than 72 hours after infusion, consider dexamethasone 10 mg IV every 24 hours. Grade 2 Symptoms require and respond to moderate intervention. Fever, oxygen requirement less than 40% fraction of inspired oxygen (FiO2), or hypotension responsive to fluids or low dose of one vasopressor, or Grade 2 organ toxicity.

Administer tocilizumab 8 mg/kg IV over 1 hour (not to exceed 800 mg). If 72 hours or more after infusion, consider dexamethasone 10 mg IV every 12-24 hours. If less than 72 hours after infusion, administer dexamethasone 10 mg IV every 12-24 hours.

If no improvement within 24 hours or […]