Table 1.
CD19-Specific CAR T Cell Therapy Toxicities
| Maude et al. (10), 2014 (N = 30) | Neelapu et al. (ZUMA-1) (13), 2017 (N= 101) | Fitzgerald et al. (25), 2017 (N= 39) | Maude et al. (ELIANA) (8), 2018 (N = 75) | Burstein et al. (24), 2018 (N = 98) | Schuster et al. (JULIET) (11,12), 2018/2019 (N = 93) | Alvi et al. (26), 2019 (N = 137) | |
|---|---|---|---|---|---|---|---|
| Cardiovascular toxicities | |||||||
| Profound hypotension requiring inotropic support or shock | 27% | 14% | 33% | 17% | 24% | 9% | 4% (6 patients developed shock leading to cardiac deaths) |
| Left ventricular systolic dysfunction | — | — | 2% | — | 10% | — | 6% |
| Pulmonary edema | — | — | — | 6% | — | — | 4% (shortness of breath, hypoxia, signs of volume overload, and NT-proBNP >3000 pg/ml) |
| Fluid overload | — | — | 5% | ||||
| ECG and rhythm abnormalities | — | — | Sinus tachycardia (median peak HR 170 beats/min) | — | ST- segment changes (18%) | — | New-onset arrhythmias including supraventricular tachycardia, atrial fibrillation, or flutter (4%) |
| Biomarker abnormalities | — | — | — | — | NT-proBNP (92%) Lactate (79%) Mixed venous saturation (52%) |
- | Troponin elevation (54%) |
| Other toxicities | |||||||
| Cytokine release syndrome | 100% | 93% | 92% | 77% | — | 58% | 59% |
| Neurotoxicity | 43% | 64% | 33% | 40% | — | 21% | — |
| Management | |||||||
| Treatment with tocilizumab | 30% | 43% | 33% | 37% | 21% | 14% | 41% |
| Treatment with corticosteroids | 20% | 27% | 21% | — | — | 10% | — |
| Treatment with cardioprotective medications | — | — | — | — | Beta-blockers (21%) ACE inhibitors (17%) |
— | — |
CD19-specific chimeric antigen receptor (CAR) T cell therapy is associated with toxicities, including cytokine release syndrome, neurotoxicity, and a number of cardiovascular complications as shown in the early pivotal trials.
— = data have not been studied or reported within the publication; ACE = angiotensin-converting enzyme; ECG = electrocardiography; ELIANA = Determine Efficacy and Safety of CTL019 in Pediatric Patients With Relapsed and Refractory B-cell ALL and High Risk B-cell ALL at First Relapse. Determine Feasibility and Safety of CTL019 Therapy in Pediatric Patients With High Risk B-cell ALL That Relapsed <6 Months Post All-HSCT; HR = heart rate; JULIET = Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients; NT-proBNP = N-terminal pro–B-type natriuretic peptide; ZUMA-1 = Long-Term Safety and Activity of Axicabtagene Ciloleucel in Refractory Large B-Cell Lymphoma.