Table 4.
Summary of outcomes and reported cardiotoxic events in the pivotal phase 2 trials leading to FDA approval of Tisgenlecleucel, Axicabtagene Ciloleucel, and Brexucabtagene Ciloleucel.
| FDA Approved CD19-CAR-T | Tisagenlecleucel | Tisagenlecleucel | Axicabtagene Ciloleucel | Brexucabtagene Autoleucel |
|---|---|---|---|---|
| Trial | JULIET [7] | ELIANA [8] | ZUMA-1 [9] | ZUMA-2 [10] |
| Disease | Adult LBCL | Pediatric B-ALL | Adult LBCL | Adult MCL |
| Study Phase | 2 | 1–2 | 2 | 2 |
| Patients Studied in Efficacy Analysis | 93 | 75 | 101 | 68 |
| Objective Response Rate | 50% | 83% | 82% | 93% |
| Complete Response | 40% | 60% | 54% | 67% |
| 12 month RFS/PFS | 65% | 59% | 44% | 61% |
| 12 month OS | 49% (estimated) | 76% | 59% | 83% |
| Patients Studied in Safety Analysis | 111 | 75 | 101 | 68 |
| Percent with any Grade AE | 100% | 100% | 100% | 100% |
| CRS | 64 (58%) | 58 (77%) | 94 (93%) | 61 (91%) |
| CRS Grading System | Penn Criteria [12] | Penn Criteria [12] | Lee Criteria [13] | Lee Criteria [13] |
| Tocilizumab Use | 16 (14%) | 36 (48%) | 49 (48.5%) | 42 (61.8%) |
| Hypotension | 29 (26%) | 22(29%) | 60 (59%) | 35 (51%) |
| Hypotension requiring inotropic support or shock | 8 (9%) | 13 (17%) | 14 (14%) | 15 (22%) |
| Pulmonary Edema | NR | 5 (6.7%) | NR | NR |
| Left Ventricular Dysfunction | NR | 3 (4.0%) | NR | NR |
| Cardiac Arrest | NR | 3(4.0%) | NR | NR |
| Cardiac Failure | NR | 2 (2.7%) | NR | NR |
| Tachycardia | 12 (11%) | 3 (4.0%) | 39 (39%) | 21 (31%) |
B-ALL: B-cell Acute Lymphoblastic Leukemia; RFS: Relapse Free Survival; PFS: Progression Free Survival; OS: Overall Survival; AE: Adverse Events; CRS: Cytokine Release syndrome; LBCL: Large B-cell Lymphoma; MCL: Mantle Cell Lymphoma.