Main trials in single antigen–targeted CAR T cells for B-cell ALL
| Reference . | Trial phase . | CAR construct . | n∗ (age range) . | In vivo expansion . | Rate of CR or CRi . | Toxicity . | Persistence . | Relapse incidence and phenotype . | EFS/OS . |
|---|---|---|---|---|---|---|---|---|---|
| B-cell ALL – CD19 | |||||||||
| Maude et al, 20184 Updated by Laetsch et al, 20216 ELIANA study | 2 | Tisa-cel FMC63 scFv – 4-1BB – Cd3z | n = 79 (3-21 y) | AUC 0-28: 318 000 mean copies per μg Cmax 34 700 copies per μg in responders7 | CR: 45/79 (60%) CRi: 16/79 (21%) 65/79 (82%) MRD– at 3 mo | CRS G3/4: 46% NTx G3/4: 13% | Median time to B-cell recovery in responders 35.3 mo BCA 12 mo: 71% BCA 24 mo: 59% | 51% (33/65) CD19+: 2/33 (6%) CD19–: 16/33 (48%) CD19+/–: 3/33 (9%) Unknown: 12/33 (36%) | Median EFS 23.7 mo EFS 44% at 3 y OS 63% at 3 y |
| Gardner et al, 20173 | 1-2 | FMC63-4-1BB-CD3z Defined 1:1 ratio of CD4+/CD8+ CAR T cells | n = 45 (1-27 y) | Peak 10 d. No correlation of peak expansion with cell dose. Higher expansion with >15% CD19 disease in marrow. | 40/45 (89%) MRD– CR by day 21 | CRS G3/4: 10/43 (23%) NTx G3/4: 9/43 (21%) | BCA ≈ 30% at 6 mo | 18/40 (45%) CD19+: 11/18 (61%) CD19–: 7/18 (39%) | Median EFS ∼13 mo EFS 50.8% at 12 mo OS 70% at 12 mo |
| Ghorashian et al, 20195 CARPALL study | 1-2 | CAT19 scFv – 4-1BB – CD3z | n = 14 (<25 y) | AUC 0-28: 1 721 355 mean copies per μg Cmax 128 012 mean copies per μg | 86% (12/14) CR MRD– at 3 mo | No G3/4 CRS NTx G3/4: 1/14 (7%) | B-cell aplasia 21% at 12 mo CAR detectable qPCR 79% (11/14) at last follow-up Median duration 215 d (14-728 d) | 50% (6/12) CD19+: 1/6 (16%) CD19–: 5/6 (83%) | Median EFS 9 mo EFS 46% at 12 mo OS 63% at 12 mo |
| Park et al , 20188 | 1 | FMC63 scFv – CD28 – CD3z | N = 53 (23-74 y) | Higher expansion in patients with preinfusion MRD– CR | 44/53 CR at day 21 32/48 MRD– | CRS G3/4: 26% (14/53) NTx G3/4/5: 22/53† | Short-persisting CAR T cells. Median duration of CAR T-cell detection: 14 d Most CAR T cells lost before day 40 | 25/53 CD19+: 21/25 (84%) CD19–: 4/25 (16%) | Median EFS 6.1 mo EFS ∼18% at 24 mo Median OS 12.9 mo |
| Shah et al, 20219 ZUMA 3 | 2 | Brexucabtagene autoleucel (KTE-X19) FMC63 scFv – CD28 – CD3z | N = 55 (28-52 y) | Median peak: 40.47 cells per μL (IQR, 6.04-76.70) | 39/55 (71%) at median of 1 mo | CRS G3/4: 13/55 (24%) NTx G3/4/5: 14/55 (25%)† | B-cell recovery in 10/12 ongoing responders at month 12 | Relapse incidence: 12/55 (22%) CD19+: 6/9 (67%) CD19–: 3/9 (33%) (only 9 patients with available data) | Median EFS 11.6 mo OS 71% at 12 mo 9/55 proceeded to HSCT |
| B-cell ALL – CD22 | |||||||||
| Fry et al, 201810 Updated and expanded by Shah et al, 202011 | 1 | Anti-CD22 m971 scFv – 4-1BB – CD3z → Shah et al incorporated CD4/CD8 selection into manufacturing | 58 (4-30 y) 36/58 (62 %) previous aCD19 CAR-T 39/58 (67%) previous HSCT | Median peak: 480.5 CAR T cells per μL (range, 39.7-11 346) | 40/57 (70%) at 1 mo | CRS G3/4: 12/58 (24%) NTx G3/4/5: 1/58 (2%) → 19/58 (33%) developed HLH (HLH incidence increased after incorporating CD4/CD8 selection at target dose) | NR | 30/58 (75%) Downregulation of cD22 expression in most patients. | Median EFS 6 mo Median OS 13.4 mo 14 patients proceeded to HSCT |
| Reference . | Trial phase . | CAR construct . | n∗ (age range) . | In vivo expansion . | Rate of CR or CRi . | Toxicity . | Persistence . | Relapse incidence and phenotype . | EFS/OS . |
|---|---|---|---|---|---|---|---|---|---|
| B-cell ALL – CD19 | |||||||||
| Maude et al, 20184 Updated by Laetsch et al, 20216 ELIANA study | 2 | Tisa-cel FMC63 scFv – 4-1BB – Cd3z | n = 79 (3-21 y) | AUC 0-28: 318 000 mean copies per μg Cmax 34 700 copies per μg in responders7 | CR: 45/79 (60%) CRi: 16/79 (21%) 65/79 (82%) MRD– at 3 mo | CRS G3/4: 46% NTx G3/4: 13% | Median time to B-cell recovery in responders 35.3 mo BCA 12 mo: 71% BCA 24 mo: 59% | 51% (33/65) CD19+: 2/33 (6%) CD19–: 16/33 (48%) CD19+/–: 3/33 (9%) Unknown: 12/33 (36%) | Median EFS 23.7 mo EFS 44% at 3 y OS 63% at 3 y |
| Gardner et al, 20173 | 1-2 | FMC63-4-1BB-CD3z Defined 1:1 ratio of CD4+/CD8+ CAR T cells | n = 45 (1-27 y) | Peak 10 d. No correlation of peak expansion with cell dose. Higher expansion with >15% CD19 disease in marrow. | 40/45 (89%) MRD– CR by day 21 | CRS G3/4: 10/43 (23%) NTx G3/4: 9/43 (21%) | BCA ≈ 30% at 6 mo | 18/40 (45%) CD19+: 11/18 (61%) CD19–: 7/18 (39%) | Median EFS ∼13 mo EFS 50.8% at 12 mo OS 70% at 12 mo |
| Ghorashian et al, 20195 CARPALL study | 1-2 | CAT19 scFv – 4-1BB – CD3z | n = 14 (<25 y) | AUC 0-28: 1 721 355 mean copies per μg Cmax 128 012 mean copies per μg | 86% (12/14) CR MRD– at 3 mo | No G3/4 CRS NTx G3/4: 1/14 (7%) | B-cell aplasia 21% at 12 mo CAR detectable qPCR 79% (11/14) at last follow-up Median duration 215 d (14-728 d) | 50% (6/12) CD19+: 1/6 (16%) CD19–: 5/6 (83%) | Median EFS 9 mo EFS 46% at 12 mo OS 63% at 12 mo |
| Park et al , 20188 | 1 | FMC63 scFv – CD28 – CD3z | N = 53 (23-74 y) | Higher expansion in patients with preinfusion MRD– CR | 44/53 CR at day 21 32/48 MRD– | CRS G3/4: 26% (14/53) NTx G3/4/5: 22/53† | Short-persisting CAR T cells. Median duration of CAR T-cell detection: 14 d Most CAR T cells lost before day 40 | 25/53 CD19+: 21/25 (84%) CD19–: 4/25 (16%) | Median EFS 6.1 mo EFS ∼18% at 24 mo Median OS 12.9 mo |
| Shah et al, 20219 ZUMA 3 | 2 | Brexucabtagene autoleucel (KTE-X19) FMC63 scFv – CD28 – CD3z | N = 55 (28-52 y) | Median peak: 40.47 cells per μL (IQR, 6.04-76.70) | 39/55 (71%) at median of 1 mo | CRS G3/4: 13/55 (24%) NTx G3/4/5: 14/55 (25%)† | B-cell recovery in 10/12 ongoing responders at month 12 | Relapse incidence: 12/55 (22%) CD19+: 6/9 (67%) CD19–: 3/9 (33%) (only 9 patients with available data) | Median EFS 11.6 mo OS 71% at 12 mo 9/55 proceeded to HSCT |
| B-cell ALL – CD22 | |||||||||
| Fry et al, 201810 Updated and expanded by Shah et al, 202011 | 1 | Anti-CD22 m971 scFv – 4-1BB – CD3z → Shah et al incorporated CD4/CD8 selection into manufacturing | 58 (4-30 y) 36/58 (62 %) previous aCD19 CAR-T 39/58 (67%) previous HSCT | Median peak: 480.5 CAR T cells per μL (range, 39.7-11 346) | 40/57 (70%) at 1 mo | CRS G3/4: 12/58 (24%) NTx G3/4/5: 1/58 (2%) → 19/58 (33%) developed HLH (HLH incidence increased after incorporating CD4/CD8 selection at target dose) | NR | 30/58 (75%) Downregulation of cD22 expression in most patients. | Median EFS 6 mo Median OS 13.4 mo 14 patients proceeded to HSCT |
AUC, area under the curve; BCA, B-cell aplasia; Cmax, peak serum concentration; CR, complete remission; CRi, complete remission with incomplete recovery; CRS, cytokine release syndrome; HLH, hemophagocytic lymphohistiocytosis; HSCT, hematopoietic stem cell transplantation; IQR, interquartile range; MRD–, negative minimal residual disease; NR, not reported; NTx, neurotoxicity; OS, overall survival; qPCR, quantitative polymerase chain reaction.
Showing the final number of patients who received infusions.
Used American Society for Transplantation and Cellular Therapy consensus criteria for CRS grading and Common Terminology Criteria for Adverse Events grading for neurotoxicity.