Main trials using CD19/CD22 dual-targeting CAR T cells for B-cell lymphomas
| Reference . | Trial phase . | CAR construct . | n∗ . | Diseases . | Patient characteristics . | Response . | In vivo expansion . | Persistence . | Progression/relapses (and relapse phenotype if available) . | EFS/OS . |
|---|---|---|---|---|---|---|---|---|---|---|
| Wang et al, 202053,† Wuhan, China | 1 | Coadministration (third-generation sequential, day 0-4) | 38 (age 9-71 y) | DLBCL NOS: 23; DH HGBL: 4; HGBL NOS: 3; FL: 3; Burkitt lymphoma: 2; PMBCL: 1; Others: 2 | Refractory: 15 First relapse: 11 Second relapse: 4 ≥third relapse: 8 Bridging: allowed, but no data | ORR: 26/36 (72%) CR: 18/36 (50%) at month 3 | NR | NR | 18/38 (7 were biopsied, showed CD19+/CD22+ disease) | 50% 12 mo PFS 55.3% 12 mo OS |
| Cao et al, 202152 Wuhan, China | 1 | High-dose chemotherapy with aHSCi, followed by aCD22 then aCD19 coadministration (days 2 and 3) | 42 (age 24-61 y) | DLBCL NOS: 30 tFL: 7 DH HGBL: 2 Others: 3 | PR: 10/42 PD: 23/42 SD: 9/42 Bridging: high-dose chemotherapy with aHSCi | ORR: 38/42 (91%) CR: 34/42 (81%) at month 3 | Peak at 1 wk | Median time to B-cell recovery 8.2 mo | 7/42 (5 were biopsied, showed CD19+/CD22+ disease) | 83% 24 mo PFS 83% 24 mo OS |
| Wu et al, 202178 Wuhan, China | 1 | High-dose chemotherapy with aHSCi followed by sequential CD19 and CD22 CART infusion for CNS | 13 (age 23-65 y) | DLBCL with CNS involvement: 8 Primary CNS DLBCL: 4 ILBCL: 1 | Refractory: 1 PR: 2 PD: 3 CNS relapse: 7 Bridging: permitted, no data available | ORR: 9/11 (82%) CR: 6/11 (55%) at month 3 | Peak at 1 wk | Median persistence <3 mo | 3/11 | 75% 12 mo PFS 83% 12 mo OS |
| Roddie et al, 202379 London, UK (ALEXANDER study) | 1 | Auto 3 Bicistronic vector Humanized CAR + pembrolizumab | 52 (age 27-83 y) | DLBCL: 36; tFL: 10; PM LBCL: 1; t nodal MZL: 1; HGBL: 3 | Previous autologous HSC: 16 Bridging: 37/51 (73%) | ORR: 31/47 (66%) CR: 23/47 (49%) at month 1 | Median peak at 12 d | Median of 4.2 mo persistence | 33/52 13 had biopsy: -Majority CD19+ -7/13 CD22lo/– -2 cases of clear CD19– (H-score heat mapping) | 26% 12 mo EFS 54% 12 mo OS |
| Spiegel et al, 202162,† Stanford, California | 1 | Tandem CAR (CD19VH – CD22 VL – CD22 VH – CD19 VL – 4-1BB) | 21 (age 25-78 y) | DLBCL: 14 tFL: 4 PMBCL: 2 Richter: 2 | Previous autologous HSC: 4 Previous CAR: none Bridging: permitted, no data available | ORR: 13/21 (62%) CR: 6/21 (29%) at month 3 | Peak at 10-14 d CD8 > CD4 expansion | NR | Relapse: 1/21 PD: 15/21 14 biopsied at progression: 4 patients CD19–/lo | 25% 12 mo PFS 65% 12 mo OS |
| Wei et al, 202180 Hangzhou, China | 1 | Tandem (VL-VH-VL-VH) | 16 (age 23-68 y) | DLBCL: 13 B-LLy: 2 Burkitt lymphoma: 1 | Previous autologous HSCT: 1 Bridging: none | ORR: 14/16 (87.5%) CR: 10/16 (62.5%) at month 1 | Peak at 5-10 d | 8/16 ongoing B-cell aplasia at 10 mo 13/16 ongoing B-cell aplasia at 6 mo | Relapse: 3/16 PD: 7/16 (2 were biopsied, showed CD19+/CD22+ disease) | 40.2% 12 mo PFS 77.3% 12 mo OS |
| Zhang et al, 202181 Suzhou, China | 1 | Tandem (CD22VL – CD19 VL – CD19 VH – CD22 VH – 4-1BB) | 32 (no age range given) <60 y: 24 ≥60 y: 8 | DLBCL: 27 tFL: 2 PMBCL: 1 HGBL: 2 | Primary refractory: 5 Previous autologous HSC: 4 Bridging: no data available | ORR: 22/29 (76%) CR: 10/29 (34%) | Peak 10-14 d Responders had higher expansion | Median 92 d persistence in peripheral blood (min, 13; max, 763) | 10/29 PD No biopsy performed at time of progression. | 40% 12 mo PFS 63% 12 mo OS |
| Zhang et al, 202382 Suzhou, China | 2 | Tandem + tislelizumab | 16 (age 19-70 y) | DLBCL: 13 Richter: 2 Burkitt lymphoma: 1 | Previous autologous HSC: 4 | ORR: 14/16 (88%) CR: 11/16 (69%) | Peak at median of 12 d | CAR T cells present in 50% of patients at 6-mo follow-up | Relapse: 2/16 PD: 3/16 | 69% 12 mo PFS 81% 12 mo OS |
| Reference . | Trial phase . | CAR construct . | n∗ . | Diseases . | Patient characteristics . | Response . | In vivo expansion . | Persistence . | Progression/relapses (and relapse phenotype if available) . | EFS/OS . |
|---|---|---|---|---|---|---|---|---|---|---|
| Wang et al, 202053,† Wuhan, China | 1 | Coadministration (third-generation sequential, day 0-4) | 38 (age 9-71 y) | DLBCL NOS: 23; DH HGBL: 4; HGBL NOS: 3; FL: 3; Burkitt lymphoma: 2; PMBCL: 1; Others: 2 | Refractory: 15 First relapse: 11 Second relapse: 4 ≥third relapse: 8 Bridging: allowed, but no data | ORR: 26/36 (72%) CR: 18/36 (50%) at month 3 | NR | NR | 18/38 (7 were biopsied, showed CD19+/CD22+ disease) | 50% 12 mo PFS 55.3% 12 mo OS |
| Cao et al, 202152 Wuhan, China | 1 | High-dose chemotherapy with aHSCi, followed by aCD22 then aCD19 coadministration (days 2 and 3) | 42 (age 24-61 y) | DLBCL NOS: 30 tFL: 7 DH HGBL: 2 Others: 3 | PR: 10/42 PD: 23/42 SD: 9/42 Bridging: high-dose chemotherapy with aHSCi | ORR: 38/42 (91%) CR: 34/42 (81%) at month 3 | Peak at 1 wk | Median time to B-cell recovery 8.2 mo | 7/42 (5 were biopsied, showed CD19+/CD22+ disease) | 83% 24 mo PFS 83% 24 mo OS |
| Wu et al, 202178 Wuhan, China | 1 | High-dose chemotherapy with aHSCi followed by sequential CD19 and CD22 CART infusion for CNS | 13 (age 23-65 y) | DLBCL with CNS involvement: 8 Primary CNS DLBCL: 4 ILBCL: 1 | Refractory: 1 PR: 2 PD: 3 CNS relapse: 7 Bridging: permitted, no data available | ORR: 9/11 (82%) CR: 6/11 (55%) at month 3 | Peak at 1 wk | Median persistence <3 mo | 3/11 | 75% 12 mo PFS 83% 12 mo OS |
| Roddie et al, 202379 London, UK (ALEXANDER study) | 1 | Auto 3 Bicistronic vector Humanized CAR + pembrolizumab | 52 (age 27-83 y) | DLBCL: 36; tFL: 10; PM LBCL: 1; t nodal MZL: 1; HGBL: 3 | Previous autologous HSC: 16 Bridging: 37/51 (73%) | ORR: 31/47 (66%) CR: 23/47 (49%) at month 1 | Median peak at 12 d | Median of 4.2 mo persistence | 33/52 13 had biopsy: -Majority CD19+ -7/13 CD22lo/– -2 cases of clear CD19– (H-score heat mapping) | 26% 12 mo EFS 54% 12 mo OS |
| Spiegel et al, 202162,† Stanford, California | 1 | Tandem CAR (CD19VH – CD22 VL – CD22 VH – CD19 VL – 4-1BB) | 21 (age 25-78 y) | DLBCL: 14 tFL: 4 PMBCL: 2 Richter: 2 | Previous autologous HSC: 4 Previous CAR: none Bridging: permitted, no data available | ORR: 13/21 (62%) CR: 6/21 (29%) at month 3 | Peak at 10-14 d CD8 > CD4 expansion | NR | Relapse: 1/21 PD: 15/21 14 biopsied at progression: 4 patients CD19–/lo | 25% 12 mo PFS 65% 12 mo OS |
| Wei et al, 202180 Hangzhou, China | 1 | Tandem (VL-VH-VL-VH) | 16 (age 23-68 y) | DLBCL: 13 B-LLy: 2 Burkitt lymphoma: 1 | Previous autologous HSCT: 1 Bridging: none | ORR: 14/16 (87.5%) CR: 10/16 (62.5%) at month 1 | Peak at 5-10 d | 8/16 ongoing B-cell aplasia at 10 mo 13/16 ongoing B-cell aplasia at 6 mo | Relapse: 3/16 PD: 7/16 (2 were biopsied, showed CD19+/CD22+ disease) | 40.2% 12 mo PFS 77.3% 12 mo OS |
| Zhang et al, 202181 Suzhou, China | 1 | Tandem (CD22VL – CD19 VL – CD19 VH – CD22 VH – 4-1BB) | 32 (no age range given) <60 y: 24 ≥60 y: 8 | DLBCL: 27 tFL: 2 PMBCL: 1 HGBL: 2 | Primary refractory: 5 Previous autologous HSC: 4 Bridging: no data available | ORR: 22/29 (76%) CR: 10/29 (34%) | Peak 10-14 d Responders had higher expansion | Median 92 d persistence in peripheral blood (min, 13; max, 763) | 10/29 PD No biopsy performed at time of progression. | 40% 12 mo PFS 63% 12 mo OS |
| Zhang et al, 202382 Suzhou, China | 2 | Tandem + tislelizumab | 16 (age 19-70 y) | DLBCL: 13 Richter: 2 Burkitt lymphoma: 1 | Previous autologous HSC: 4 | ORR: 14/16 (88%) CR: 11/16 (69%) | Peak at median of 12 d | CAR T cells present in 50% of patients at 6-mo follow-up | Relapse: 2/16 PD: 3/16 | 69% 12 mo PFS 81% 12 mo OS |
aHSCi, autologous hematopoietic stem cell infusion; B-LLy, B-cell lymphoblastic lymphoma; CAR, chimeric antigen receptor; CNS, central nervous system; CR, complete remission; DH HGBL, double-hit high-grade lymphoma; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; HGBL, high-grade B-cell lymphoma; HSC, hematopoietic stem cell; HSCT, hematopoietic stem cell transplantation; ILBCL, intravascular large B-cell lymphoma; MZL, marginal-zone lymphoma; NOS, not otherwise specified; NR, not reported; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PMBCL, primary mediastinal B-cell lymphoma; PM LBCL, primary mediastinal large B-cell lymphoma; PR, partial remission; SD, stable disease; tFL, transformed follicular lymphoma; VH, variable heavy chain; VL, variable light chain.
Showing the final number of patients who received infusions.
Showing results for the B-cell lymphoma cohort only.