Summary of the safety profile Safety assessment was based on a total of 424 patients (with paediatric and young adult B-cell ALL, DLBCL and FL) who received Kymriah in three multicentre pivotal clinical studies. B-cell ALL The adverse reactions described in this section were characterised in 212 patients infused with Kymriah in the pivotal clinical study CCTL019B2202 and in the supportive studies CCTL019B2205J and CCTL019B2001X.
The most common non-haematological adverse reactions were cytokine release syndrome (75%), infections (70%), hypogammaglobulinaemia (49%), pyrexia (43%) and decreased appetite (28%). The most common haematological laboratory abnormalities were decreased white blood cells (100%), decreased haemoglobin (99%), decreased neutrophils (98%), decreased lymphocytes (98%) and decreased platelets (95%).
Grade 3 and 4 adverse reactions were reported in 86% of patients. The most common Grade 3 and 4 non-haematological adverse reaction was cytokine release syndrome (37%). The most common Grade 3 and 4 haematological laboratory abnormalities were white blood cells decreased (97%), lymphocytes decreased (94%), neutrophils decreased (96%), platelets decreased (70%) and haemoglobin decreased (46%).
Grade 3 and 4 adverse reactions were more often observed within the initial 8 weeks post infusion (78% of patients) compared to after 8 weeks post infusion (49% of patients). e. the ongoing pivotal clinical study CCTL019C2201. The most common non-haematological adverse reactions were cytokine release syndrome (57%), infections (58%), pyrexia (35%), diarrhoea (31%), nausea (29%), fatigue (27%) and hypotension (25%).
The most common haematological laboratory abnormalities were decreased lymphocytes (100%), decreased white blood cells (99%), decreased haemoglobin (99%), decreased neutrophils (97%), and decreased platelets (95%). 12 Grade 3 and 4 adverse reactions were reported in 88% of patients.
The most common Grade 3 and 4 non-haematological adverse reactions were infections (34%) and cytokine release syndrome (23%). The most common (>25%) Grade 3 and 4 haematological laboratory abnormalities were lymphocyte count decreased (95%), neutrophil count decreased (82%), white blood cell count decreased (78%), haemoglobin decreased (59%) and platelet count decreased (56%).
Grade 3 and 4 adverse reactions were more often observed within the initial 8 weeks post infusion (82%) compared to after 8 weeks post infusion (48%). e. the ongoing pivotal clinical study CCTL019E2202. The most common non-haematological adverse reactions (>25%) were cytokine release syndrome (50%), infections (50%) and headache (26%).
The most common haematological laboratory abnormalities were decreased haemoglobin (94%), decreased lymphocytes (92%), decreased white blood cells (91%), decreased neutrophils (89%) and decreased platelets (89%). Grade 3 and 4 adverse reactions were reported in 75% of patients.
The most common Grade 3 and 4 non-haematological adverse reactions were infections (16%). The most common (>25%) Grade 3 and 4 haematological laboratory abnormalities were lymphocyte count decreased (87%), white blood cell count decreased (74%), neutrophil count decreased (71%), platelet count decreased (26%) and haemoglobin decreased (25%).
Grade 3 and 4 adverse reactions were more often observed within the initial 8 weeks post infusion (70%) compared to after 8 weeks post infusion (40%). Tabulated list of adverse reactions The adverse reactions described in this section were identified in 79, 115 and 97 patients in the ongoing multicentre pivotal clinical studies (CCTL019B2202, CCTL019C2201 and CCTL019E2202), as well as 64 and 69 patients in the supportive studies (CCTL019B2205J and CCTL019B2001X), and from post-marketing reporting.
Adverse drug reactions (Table 1) are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first, using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000); not known (cannot be estimated from the available data).
Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness.
Table 1 Adverse drug reactions Infections and infestations1) Very common:
Infections - pathogen unspecified, viral infections, bacterial infections Common: Fungal infections Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rare: Secondary malignancy of T-cell origin Blood and lymphatic system disorders Very common: Anaemia, febrile neutropenia, neutropenia, thrombocytopenia Common: Leukopenia, pancytopenia, coagulopathy, lymphopenia Uncommon: B-cell aplasia 13 Immune system disorders Very common: Cytokine release syndrome, hypogammaglobulinaemia2) Common: Infusion-related reaction, graft-versus-host disease3), haemophagocytic lymphohistiocytosis Not known: Anaphylactic reaction Metabolism and nutrition disorders Very common: Decreased appetite, hypokalaemia, hypophosphataemia Common: Hypomagnesaemia, hypoalbuminaemia4), hyperglycaemia, hyponatraemia, hyperuricaemia5), hypercalcaemia, tumour lysis syndrome, hyperkalaemia, hyperphosphataemia6), hypernatraemia, hyperferritinaemia7), hypocalcaemia Uncommon: Hypermagnesaemia Psychiatric disorders Common: Anxiety, delirium8), sleep disorder9) Nervous system disorders Very common: Headache10), encephalopathy11) Common: Dizziness12), peripheral neuropathy13), tremor14), motor dysfunction15), seizure16), immune effector cell-associated neurotoxicity syndrome**, speech disorders17), neuralgia18) Uncommon: […]