Main trials using dual-targeting CAR T cells for CD19 and CD22 in B-cell ALL
| Reference . | Trial phase . | CAR construct . | n∗ . | In vivo expansion . | Rate of CR . | Relapse phenotype . | Persistence . | EFS/OS . | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| CD19+ CD22+ . | CD19+ CD22– . | CD19– CD22+ . | CD19– CD22– . | ||||||||
| Wang et al, 202053,† Wuhan, China | 1 | Coadministration Third-generation CAR Sequential, day 0-4 | 51 (age 9-62 y) | — | 48/51 (96%) on day 30 | 23/24 | 0 | 0 | 1/24 (CD19–/CD22dim) | Short persistence (4 mo median time to recovery of bone marrow B-cell hematogones) | 53% 12 mo RFS |
| Pan et al, 202155 Beijing, China | 1 | Coadministration Sequential, separated by 1.65 mo, once CAR19 undetectable | 20 (age 1-16 y) | — | 20/20 (100%) MRD-negative on day 28 | 1/3 (downregulation) | 0 | 2/3 | 0 | Good persistence (17/20 patients showed >1 y CAR T-cell persistence) | 80% 18 mo RFS |
| Liu et al, 202156 Beijing, China | 1 | Coadministration Sequential, separated by at least 1 mo | 27 infusion 1 21 infusion 2 (age 1.6-55 y) | Similar expansion after CD19 product and CD22 | 23/27 CR after infusion 1 20/21 CR after infusion 2 | 4/21 | 0 | 2/21 | 0 | B-cell aplasia (median): 10 mo 75% lost CD22 CAR T cells on day 60 50% had CD19 CARs on day 60 | 65% 18 mo EFS 84% 18 mo OS |
| Wang et al, 202250 Shanghai, China | 2 | Coadministration Second-generation CAR Pooled 1:1 7-d manufacture | 225 (<20 y) | Earlier and more robust expansion for CD19-CAR T cells | 192/194 (99%) MRD-negative on day 28 | 24/43 | 0 | 16/43 | 1/43 | B-cell recovery: - median 74 d −60% by 6 mo | 74% 12 mo EFS 88% 12 mo OS |
| Zhang et al, 202254 Tianjin, China | 1 | Coadministration Sequential, days 1 and 2. HIB22 CD22 CAR | 4 (age 18-40 y) | Peak 14-21 d | 4/4 (100%) MRD-negative on day 28 | 2/4 | 0 | 0 | 1/4 (CD19–/CD22dim) | 9 mo CAR T-cell presence in peripheral blood of 2 patients alive and without HSCT. Both relapsed with CD19 and CD22 expression. | 25% 18 mo EFS 50% 18 mo OS |
| Pan et al, 202357 Beijing, China | 2 | Coadministration Sequential, separated by 39 d CD19 murine CD22 humanized | 81 (79 received both infusions) (age 1-18 y) | CD19: peak at 9 d CD22: peak at 12 d Peak not related to dose or bone marrow burden | 79/81 (98%) MRD-negative or CRi at 3 mo | 11/79 | 0 | 2/79 | 1/79 | 20% B-cell recovery at 12 mo 40% CAR T-cell loss at 12 mo (as undetectable CAR transgene) | 79% 18 mo EFS 96% 18 mo OS |
| Gardner et al, 201858 (PLAT-05, SCRI-CAR19x22v1) Seattle, Washington | 1 | Cotransduction aCD19(FMC63)-4-1BBz aCD22(m971)4-1BBz | 7 | Selective expansion of CD19 components
| 4/7 (57%) MRD negative on day 21 | 1/4 | 0 | 2/4 | 1/4 | — | No follow-up time reported |
| Annesley et al, 202159 (PLAT-05, SCRI-CAR19x22v2) Seattle, Washington | 1 | Cotransduction | 12 | Product skewed toward CD22. In vivo expansion mostly CD22 | 11/12 (91%) MRD negative | — | — | — | — | — | No follow-up available yet |
| Ghorashian et al, 202460 (CARPALL study) London, UK | 1 | Cotransduction aCD22-9A8-4-1BBz aCD19-CAT-4-1BBz | 12 (<24 y) | Balanced expansion of all 3 components | 10/12 (83%) MRD-negative at 2 mo (molecular MRD) | 5/10 | 0 | 0 | 0 | qPCR in blood (median):
| 60% 12 mo EFS 75% 12 mo OS |
| Cordoba et al, 202149 London, UK (AMELIA study) | 1 | Bicistronic vector Humanized CAR (AUTO3) | 15 (age 4-16 y) | Kinetics of expansion like tisa-cel | 13/15 (86%) MRD-negative at 2 mo | 6/13 | 0 | 2/13 | 1/13 | 119 d median time to last detection in blood (lower than tisa-cel) | 32% 12 mo EFS |
| Dai et al, 202061 Beijing, China | 1 | Tandem CAR | 6 (age 17-44 y) | Peak at 2 wk | 6/6 (100%) MRD-negative at 1 mo | 2/6 | 1/6 (CD19–/CD22dim) | 5/6 patients <6 mo persistence | |||
| Spiegel et al, 202162,† Stanford, California | 1 | Tandem CAR | 17 (age 25-78 y) | Peak at 10-14 d Higher expansion of CD8 compared with CD4 | 15/17 (88%) MRD-negative at 6 mo (10−4 sensitivity) | 4/15 (1 no CD22 status reported) | 0 | 4/15 | 0 | All CAR-T present at day 60. No measurements undertaken thereafter. | 33% 6 mo EFS |
| Hu et al, 202163 Hangzhou, China | 1 | Tandem CAR Universal CRISPR/Cas9-engineered | 6 (age 26-56 y) | Peak at 10-14 d | 5/6 (83%) MRD-negative on day 28 | 0 | 1/6 (CD19+/CD22dim) | 0 | 0 | Patients with ongoing remission (2 patients) persistent CAR T cells >90 d Relapsed patient lost CAR T cells <60 d | - |
| Cui et al, 202364 Suzhou, China | ½ | Tandem CAR CD22 VL – CD19 VH, VL – CD22 VH – 4-1BB | 47 (age 6-56 y) | — | 40/47 (85%) MRD-negative on day 28 | 10/47 | 0 | 2/47 | 0 | 35 patients (75%) underwent consolidative HSCT at median of 2 mo from CAR T-cell infusion | 69% 24 mo RFS 74% 24 mo OS |
| Niu et al, 202365 Shanghai, China | 1 | Tandem CAR CD19 VL – CD22 VH – VL – CD19 VH – 4-1BB | 15 (age 23-70 y) First-line MRD-positive patients and relapsed MRD-positive patients | Peak at 10 d. Higher in patients with sustained remission than in those who relapsed. | 14/15 (94%) MRD-negative on day 28 | 4/15 | 0 | 1/15 | 0 | 3 patients with CAR T-cell persistence >90 d | 77% 12 mo RFS 86% 12 mo OS |
| Shalabi et al, 202266 Bethesda, Maryland | 1 | Tandem CAR | 20 (age 5-34 y) | Lower expansion than CD22 CAR alone | 16/20 (80%) MRD-negative at 1 mo (but 4 patients residual or progressive EMD) | 3/12 (CD19+, no CD22 status reported) | 0 | 0 | 1/12 (CD19–, no CD22 status reported) | Less persistence compared with patients receiving CD22 CAR alone (median 28 vs 88 d) | 58% 12 mo RFS in responders |
| Reference . | Trial phase . | CAR construct . | n∗ . | In vivo expansion . | Rate of CR . | Relapse phenotype . | Persistence . | EFS/OS . | |||
|---|---|---|---|---|---|---|---|---|---|---|---|
| CD19+ CD22+ . | CD19+ CD22– . | CD19– CD22+ . | CD19– CD22– . | ||||||||
| Wang et al, 202053,† Wuhan, China | 1 | Coadministration Third-generation CAR Sequential, day 0-4 | 51 (age 9-62 y) | — | 48/51 (96%) on day 30 | 23/24 | 0 | 0 | 1/24 (CD19–/CD22dim) | Short persistence (4 mo median time to recovery of bone marrow B-cell hematogones) | 53% 12 mo RFS |
| Pan et al, 202155 Beijing, China | 1 | Coadministration Sequential, separated by 1.65 mo, once CAR19 undetectable | 20 (age 1-16 y) | — | 20/20 (100%) MRD-negative on day 28 | 1/3 (downregulation) | 0 | 2/3 | 0 | Good persistence (17/20 patients showed >1 y CAR T-cell persistence) | 80% 18 mo RFS |
| Liu et al, 202156 Beijing, China | 1 | Coadministration Sequential, separated by at least 1 mo | 27 infusion 1 21 infusion 2 (age 1.6-55 y) | Similar expansion after CD19 product and CD22 | 23/27 CR after infusion 1 20/21 CR after infusion 2 | 4/21 | 0 | 2/21 | 0 | B-cell aplasia (median): 10 mo 75% lost CD22 CAR T cells on day 60 50% had CD19 CARs on day 60 | 65% 18 mo EFS 84% 18 mo OS |
| Wang et al, 202250 Shanghai, China | 2 | Coadministration Second-generation CAR Pooled 1:1 7-d manufacture | 225 (<20 y) | Earlier and more robust expansion for CD19-CAR T cells | 192/194 (99%) MRD-negative on day 28 | 24/43 | 0 | 16/43 | 1/43 | B-cell recovery: - median 74 d −60% by 6 mo | 74% 12 mo EFS 88% 12 mo OS |
| Zhang et al, 202254 Tianjin, China | 1 | Coadministration Sequential, days 1 and 2. HIB22 CD22 CAR | 4 (age 18-40 y) | Peak 14-21 d | 4/4 (100%) MRD-negative on day 28 | 2/4 | 0 | 0 | 1/4 (CD19–/CD22dim) | 9 mo CAR T-cell presence in peripheral blood of 2 patients alive and without HSCT. Both relapsed with CD19 and CD22 expression. | 25% 18 mo EFS 50% 18 mo OS |
| Pan et al, 202357 Beijing, China | 2 | Coadministration Sequential, separated by 39 d CD19 murine CD22 humanized | 81 (79 received both infusions) (age 1-18 y) | CD19: peak at 9 d CD22: peak at 12 d Peak not related to dose or bone marrow burden | 79/81 (98%) MRD-negative or CRi at 3 mo | 11/79 | 0 | 2/79 | 1/79 | 20% B-cell recovery at 12 mo 40% CAR T-cell loss at 12 mo (as undetectable CAR transgene) | 79% 18 mo EFS 96% 18 mo OS |
| Gardner et al, 201858 (PLAT-05, SCRI-CAR19x22v1) Seattle, Washington | 1 | Cotransduction aCD19(FMC63)-4-1BBz aCD22(m971)4-1BBz | 7 | Selective expansion of CD19 components
| 4/7 (57%) MRD negative on day 21 | 1/4 | 0 | 2/4 | 1/4 | — | No follow-up time reported |
| Annesley et al, 202159 (PLAT-05, SCRI-CAR19x22v2) Seattle, Washington | 1 | Cotransduction | 12 | Product skewed toward CD22. In vivo expansion mostly CD22 | 11/12 (91%) MRD negative | — | — | — | — | — | No follow-up available yet |
| Ghorashian et al, 202460 (CARPALL study) London, UK | 1 | Cotransduction aCD22-9A8-4-1BBz aCD19-CAT-4-1BBz | 12 (<24 y) | Balanced expansion of all 3 components | 10/12 (83%) MRD-negative at 2 mo (molecular MRD) | 5/10 | 0 | 0 | 0 | qPCR in blood (median):
| 60% 12 mo EFS 75% 12 mo OS |
| Cordoba et al, 202149 London, UK (AMELIA study) | 1 | Bicistronic vector Humanized CAR (AUTO3) | 15 (age 4-16 y) | Kinetics of expansion like tisa-cel | 13/15 (86%) MRD-negative at 2 mo | 6/13 | 0 | 2/13 | 1/13 | 119 d median time to last detection in blood (lower than tisa-cel) | 32% 12 mo EFS |
| Dai et al, 202061 Beijing, China | 1 | Tandem CAR | 6 (age 17-44 y) | Peak at 2 wk | 6/6 (100%) MRD-negative at 1 mo | 2/6 | 1/6 (CD19–/CD22dim) | 5/6 patients <6 mo persistence | |||
| Spiegel et al, 202162,† Stanford, California | 1 | Tandem CAR | 17 (age 25-78 y) | Peak at 10-14 d Higher expansion of CD8 compared with CD4 | 15/17 (88%) MRD-negative at 6 mo (10−4 sensitivity) | 4/15 (1 no CD22 status reported) | 0 | 4/15 | 0 | All CAR-T present at day 60. No measurements undertaken thereafter. | 33% 6 mo EFS |
| Hu et al, 202163 Hangzhou, China | 1 | Tandem CAR Universal CRISPR/Cas9-engineered | 6 (age 26-56 y) | Peak at 10-14 d | 5/6 (83%) MRD-negative on day 28 | 0 | 1/6 (CD19+/CD22dim) | 0 | 0 | Patients with ongoing remission (2 patients) persistent CAR T cells >90 d Relapsed patient lost CAR T cells <60 d | - |
| Cui et al, 202364 Suzhou, China | ½ | Tandem CAR CD22 VL – CD19 VH, VL – CD22 VH – 4-1BB | 47 (age 6-56 y) | — | 40/47 (85%) MRD-negative on day 28 | 10/47 | 0 | 2/47 | 0 | 35 patients (75%) underwent consolidative HSCT at median of 2 mo from CAR T-cell infusion | 69% 24 mo RFS 74% 24 mo OS |
| Niu et al, 202365 Shanghai, China | 1 | Tandem CAR CD19 VL – CD22 VH – VL – CD19 VH – 4-1BB | 15 (age 23-70 y) First-line MRD-positive patients and relapsed MRD-positive patients | Peak at 10 d. Higher in patients with sustained remission than in those who relapsed. | 14/15 (94%) MRD-negative on day 28 | 4/15 | 0 | 1/15 | 0 | 3 patients with CAR T-cell persistence >90 d | 77% 12 mo RFS 86% 12 mo OS |
| Shalabi et al, 202266 Bethesda, Maryland | 1 | Tandem CAR | 20 (age 5-34 y) | Lower expansion than CD22 CAR alone | 16/20 (80%) MRD-negative at 1 mo (but 4 patients residual or progressive EMD) | 3/12 (CD19+, no CD22 status reported) | 0 | 0 | 1/12 (CD19–, no CD22 status reported) | Less persistence compared with patients receiving CD22 CAR alone (median 28 vs 88 d) | 58% 12 mo RFS in responders |
CR, complete remission; CRi, complete remission with incomplete recovery; EMD, extramedullary disease; HSCT, hematopoietic stem cell transplantation; MRD, minimal residual disease; OS, overall survival; qPCR, quantitative polymerase chain reaction; RFS, relapse-free survival; VH, variable heavy chain; VL, variable light chain.
Showing the final number of patients who received infusions.
Showing results for the B-cell ALL cohort only.