Table 3.
Specific AEs of interest occurring within 8 weeks after tisagenlecleucel infusion in >1 patient
| Specific AEs of interest, n (%) | All infused patients (n=137) | ||
| Any grade | Grade 3 | Grade 4 | |
| CRS* | 108 (79) | 27 (20) | 30 (22) |
| Neurologic events† | 50 (36)‡ | 14 (10)§ | 0 |
| Confusion | 13 (9) | 0 | 0 |
| Encephalopathy | 12 (9) | 6 (4) | 0 |
| Delirium | 11 (8) | 3 (2) | 0 |
| Agitation | 7 (5) | 0 | 0 |
| Tremor | 7 (5) | 0 | 0 |
| Somnolence | 6 (4) | 2 (1) | 0 |
| Hallucination | 5 (4) | 0 | 0 |
| Irritability | 5 (4) | 0 | 0 |
| Seizure | 5 (4) | 2 (1) | 0 |
| Mental status changes | 4 (3) | 1 (1) | 0 |
| Cognitive disorder | 3 (2) | 1 (1) | 0 |
| Dysarthria | 3 (2) | 1 (1) | 0 |
| Lethargy | 3 (2) | 0 | 0 |
| Muscular weakness | 3 (2) | 1 (1) | 0 |
| Depressed level of consciousness | 2 (1) | 1 (1) | 0 |
| Dysphagia | 2 (1) | 2 (1) | 0 |
| Febrile neutropenia¶ | 46 (34) | 44 (32) | 2 (1) |
| Prolonged cytopenias** | 55 (40) | 21 (15) | 25 (18) |
| Prolonged white cell count decrease | 23 (17) | 7 (5) | 11 (8) |
| Prolonged neutrophil count decrease | 15 (11) | 2 (1) | 11 (8) |
| Prolonged platelet count decrease | 15 (11) | 4 (3) | 8 (6) |
| Prolonged thrombocytopenia | 11 (8) | 3 (2) | 7 (5) |
| Prolonged anemia | 9 (7) | 5 (4) | 0 |
| Prolonged lymphocyte count decrease | 9 (7) | 3 (2) | 3 (2) |
| Prolonged neutropenia | 7 (5) | 2 (1) | 4 (3) |
| Prolonged febrile neutropenia¶ | 4 (3) | 4 (3) | 0 |
| Prolonged lymphopenia | 2 (1) | 2 (1) | 0 |
| Prolonged pancytopenia | 2 (1) | 2 (1) | 0 |
| Infections¶ | 58 (42) | 22 (16) | 4 (3) |
| Viral infectious disorders | 19 (14) | 5 (4) | 1 (1) |
| Rhinovirus infection | 5 (4) | 0 | 0 |
| Oral herpes | 2 (1) | 1 (1) | 0 |
| Herpes simplex | 2 (1) | 1 (1) | 0 |
| Human herpesvirus 6 infection | 2 (1) | 1 (1) | 0 |
| Encephalitis viral | 2 (1) | 1 (1) | 1 (1) |
| Gastroenteritis norovirus | 2 (1) | 0 | 0 |
| Bacterial infectious disorders | 24 (18) | 13 (9) | 0 |
| Staphylococcal infection | 7 (5) | 3 (2) | 0 |
| Staphylococcal bacteremia | 3 (2) | 3 (2) | 0 |
| Clostridium difficile infection | 5 (4) | 3 (2) | 0 |
| Clostridium difficile colitis | 4 (3) | 1 (1) | 0 |
| Fungal infectious disorders | 8 (6) | 2 (1) | 1 (1) |
| Candida infection | 3 (2) | 0 | 1 (1) |
| Oral candidiasis | 2 (1) | 0 | 0 |
| Infections-pathogen unspecified | 29 (21) | 8 (6) | 2 (1) |
| Conjunctivitis | 5 (4) | 0 | 0 |
| Pneumonia | 3 (2) | 2 (1) | 0 |
| Oral infection | 2 (1) | 0 | 0 |
| Gastroenteritis | 2 (1) | 1 (1) | 0 |
| Nail infection | 2 (1) | 0 | 0 |
| Tumor lysis syndrome | 5 (4) | 5 (4) | 0 |
*Graded according to the University of Pennsylvania grading scale.21 22
†Neurologic events is a group term for events under the standard Medical Dictionary for Regulatory Activities queries for non-infectious encephalopathy and delirium; headache is not included in the definition. The specific events listed are those that occurred in >1 patient.
‡Twelve grade 1/2 neurologic events in eight patients were unresolved at time of death (n=6) or data cut-off (n=2). Median duration was 23 (range, 1‒62) days. Five events were assessed as related to tisagenlecleucel (confusion, encephalopathy, dysarthria, tremor, and agitation).
§Two grade 3 neurologic events in two patients were unresolved at time of death: muscular weakness (8 days) and dysarthria (8 days); neither was assessed as related to tisagenlecleucel.
¶Compared with febrile neutropenia reported as an AE, grade 3/4 neutropenia with fever ≥38.3°C occurred in 63% of patients within 8 weeks after infusion.
**Prolonged cytopenias are defined as grade 3/4 cytopenias that are not resolved to grade ≤2 by day 28 postinfusion. The specific events listed are those that occurred in >1 patient.
AE, adverse event; CRS, cytokine-release syndrome.