Table 1.
Most reported adverse events for CAR-T therapies in EudraVigilance and FAERS
| Tisagenlecleucel | Axicabtagene ciloleucel | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| FAERS | EudraVigilance | FAERS | EudraVigilance | ||||||||
| Events | N | % | Events | N | % | Events | N | % | Events | N | % |
| *Cytokine release syndrome | 185 | 8.16 | *Cytokine release syndrome | 137 | 8.58 | *Cytokine release syndrome | 462 | 14.37 | *Cytokine release syndrome | 498 | 18.79 |
| *Pyrexia | 124 | 5.47 | *Pyrexia | 90 | 5.64 | *Neurotoxicity | 312 | 9·70 | *Neurotoxicity | 247 | 9·32 |
| Malignant neoplasm progression | 61 | 2.69 | *Hypotension | 49 | 3.07 | *Pyrexia | 204 | 6.35 | *Pyrexia | 187 | 7.06 |
| *Neurotoxicity | 60 | 2.65 | *Neurotoxicity | 43 | 2.69 | *Encephalopathy | 110 | 3.42 | *Encephalopathy | 94 | 3.55 |
| *Hypotension | 53 | 2.34 | Malignant neoplasm progression | 37 | 2.32 | *Hypotension | 89 | 2.77 | *Hypotension | 75 | 2.83 |
| Acute lymphocytic leukemia recurrent | 40 | 1.76 | Acute lymphocytic leukemia recurrent | 33 | 2.07 | *Aphasia | 66 | 2.05 | *Tachycardia | 63 | 2.38 |
| *Headache | 32 | 1.41 | *White blood cell count decreased | 24 | 1.5 | *Tachycardia | 63 | 1.96 | #CAR T-cell encephalopathy syndrome | 53 | 2.0 |
| *Tachycardia | 31 | 1.37 | *Febrile neutropenia | 22 | 1.38 | #Confusional state | 58 | 1.80 | *Aphasia | 44 | 1.66 |
| *Febrile neutropenia | 29 | 1.28 | *Hypoxia | 21 | 1.31 | *Neutropenia | 57 | 1.77 | #Confusional state | 43 | 1.62 |
| *Neutrophil count decreased | 27 | 1.19 | *Platelet count decreased | 20 | 1.25 | *Tremor | 54 | 1.68 | *Neutropenia | 43 | 1.62 |
| *Hypoxia | 27 | 1.19 | *Headache | 19 | 1.19 | *Headache | 41 | 1.28 | *Tremor | 41 | 1.55 |
| *Fatigue | 25 | 1.10 | *Neutrophil count decreased | 19 | 1.19 | #Somnolence | 41 | 1.28 | *Fatigue | 38 | 1.43 |
| Drug ineffective | 23 | 1.01 | Diffuse large B-cell lymphoma | 18 | 1.13 | #Car T-cell encephalopathy syndrome | 41 | 1.28 | *Headache | 38 | 1.43 |
| *Coagulopathy | 23 | 1.01 | *Acute kidney injury | 17 | 1.06 | *Hypoxia | 39 | 1.21 | *Hypoxia | 33 | 1.25 |
| *Platelet count decreased | 22 | 0.97 | *Tachycardia | 17 | 1.06 | *Fatigue | 37 | 1.15 | *Thrombocytopenia | 30 | 1.13 |
| *Confusional state | 18 | 0.79 | Acute lymphocytic leukemia | 16 | 1.0 | *Thrombocytopenia | 36 | 1.12 | #Somnolence | 28 | 1.06 |
| *Neutropenia | 17 | 0.75 | *Coagulopathy | 15 | 0.94 | *Disorientation | 28 | 0.87 | Diffuse large B-cell lymphoma | 25 | 0.94 |
| *Hypogammaglobulinaemia | 17 | 0.75 | *Encephalopathy | 15 | 0.94 | *Atrial fibrillation | 26 | 0.81 | Death | 24 | 0.91 |
| *Encephalopathy | 16 | 0.71 | *Blood fibrinogen decreased | 14 | 0.88 | #Mental status changes | 26 | 0.81 | *Malaise | 24 | 0.91 |
| #C-Reactive protein increased | 16 | 0.71 | Drug ineffective | 14 | 0.88 | Disease progression | 26 | 0.81 | Disease progression | 19 | 0.72 |
| *Serum ferritin increased | 16 | 0.71 | *Fatigue | 14 | 0.88 | *Nausea | 25 | 0.78 | *Disorientation | 18 | 0.68 |
| Death | 15 | 0.66 | *Lymphopenia | 14 | 0.88 | #Pancytopenia | 23 | 0.72 | #Mental status changes | 18 | 0.68 |
| *Nausea | 15 | 0.66 | *Serum ferritin increased | 14 | 0.88 | *Febrile neutropenia | 23 | 0.72 | *Atrial fibrillation | 16 | 0.6 |
| Diffuse large B-cell lymphoma | 14 | 0.62 | #C-reactive protein increased | 13 | 0.81 | *Malaise | 22 | 0.68 | *Chills | 16 | 0.6 |
| *Cytopenia | 14 | 0.62 | Sepsis | 13 | 0.81 | *Vomiting | 20 | 0.62 | *Nausea | 16 | 0.6 |
| Acute lymphocytic leukemia | 14 | 0.62 | Disease progression | 12 | 0.75 | *Agitation | 20 | 0.62 | *Agitation | 15 | 0.57 |
| *Dyspnea | 13 | 0.57 | *Nausea | 12 | 0.75 | Diffuse large B-cell lymphoma | 20 | 0.62 | #Pancytopenia | 15 | 0.57 |
| *Respiratory failure | 13 | 0.57 | *Confusional state | 11 | 0.69 | Death | 18 | 0.56 | *Hypogammaglobulinaemia | 14 | 0.53 |
| *Diarrhea | 12 | 0.53 | *Neutropenia | 11 | 0.69 | #Memory impairment | 17 | 0.53 | Dysgraphia | 13 | 0.49 |
| *Acute kidney injury | 12 | 0.53 | *Disseminated intravascular coagulation | 10 | 0.63 | *Chills | 17 | 0.53 | *Vomiting | 13 | 0.49 |
| #White blood cell count decreased | 12 | 0.53 | *Anemia | 9 | 0.56 | Dysphagia | 17 | 0.53 | C-reactive protein increased | 12 | 0.45 |
| Therapy non-responder | 12 | 0.53 | #B-cell aplasia | 9 | 0.56 | #Transaminases increased | 17 | 0.53 | *Diarrhea | 12 | 0.45 |
| #Malaise | 11 | 0.49 | *Pancytopenia | 9 | 0.56 | *Hemophagocytic lymphohistiocytosis | 17 | 0.53 | Dysphagia | 12 | 0.45 |
| B-cell type acute leukemia | 11 | 0.49 | Death | 8 | 0.5 | Dysgraphia | 17 | 0.53 | #Memory impairment | 12 | 0.45 |
| *Cough | 10 | 0.44 | *Lymphocyte count decreased | 8 | 0.5 | *Pleural effusion | 16 | 0.50 | #Neutrophil count decreased | 12 | 0.45 |
| *Vomiting | 10 | 0.44 | *Multiple organ dysfunction syndrome | 8 | 0.5 | *Hyponatremia | 14 | 0.44 | *Seizure | 12 | 0.45 |
| *Multiple organ dysfunction syndrome | 10 | 0.44 | *Respiratory failure | 8 | 0.5 | Incontinence | 14 | 0.44 | #Tachypnea | 12 | 0.45 |
| *Fluid overload | 10 | 0.44 | *Chills | 7 | 0.44 | C-Reactive protein increased | 14 | 0.44 | #Transaminases increased | 12 | 0.45 |
| *Pain | 9 | 0.40 | *Hypertension | 7 | 0.44 | *Anemia | 13 | 0.40 | *Anemia | 11 | 0.42 |
| *Mental status changes | 9 | 0.40 | *International normalized ratio increased | 7 | 0.44 | *Seizure | 13 | 0.40 | #Bone marrow failure | 11 | 0.42 |
| *Decreased appetite | 9 | 0.40 | Pneumonia | 7 | 0.44 | *Abdominal pain | 13 | 0.40 | *Infection | 11 | 0.42 |
| *Seizure | 9 | 0.40 | *Abdominal pain | 6 | 0.38 | #Tachypnea | 13 | 0.40 | #White blood cell count decreased | 11 | 0.42 |
| *Pancytopenia | 9 | 0.40 | #Prolonged partial thromboplastin time | 6 | 0.38 | *Cytopenia | 13 | 0.40 | Incontinence | 10 | 0.38 |
| *Tremor | 9 | 0.40 | *Blood creatinine increased | 6 | 0.38 | *Cardiac arrest | 11 | 0.34 | Muscular weakness | 10 | 0.38 |
| *Chills | 9 | 0.40 | *Diarrhea | 6 | 0.38 | #Asthenia | 11 | 0.34 | *Pleural effusion | 10 | 0.38 |
| Disease progression | 9 | 0.40 | *Fibrin D dimer increased | 6 | 0.38 | *Infection | 11 | 0.34 | *Cytopenia | 9 | 0.34 |
| *Delirium | 9 | 0.40 | *Fluid overload | 6 | 0.38 | Sepsis | 10 | 0.31 | *Febrile neutropenia | 9 | 0.34 |
| Sepsis | 8 | 0.35 | *Hemoglobin decreased | 6 | 0.38 | Pneumonia | 10 | 0.31 | *Acute kidney injury | 8 | 0.3 |
| *Myalgia | 8 | 0.35 | *Malaise | 6 | 0.38 | *Delirium | 10 | 0.31 | #Depressed level of consciousness | 8 | 0.3 |
| *Somnolence | 8 | 0.35 | *Mental status changes | 6 | 0.38 | #White blood cell count decreased | 10 | 0.31 | Disseminated intravascular coagulation | 8 | 0.3 |
N number of reports
*Event listed in the Summary of Product Characteristic (SPC)
#Event not reported in the SPC as such but linked to other listed events