Main trials using CD19/CD20 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 . |
|---|---|---|---|---|---|---|---|---|---|---|
| Sang et al, 202051 Xuzhou, China | 2 | Coadministration, same day
| 21 (age 23-72 y) | DLBCL: 21 | Refractoryv: 15 Previous autologous HSC: 1 Previous CAR-T: none Bridging: none | ORR: 17/21 (81%) CR: 11/21 (52%) At day 90 | Higher expansion in patients with response. No difference between CD19 and CD20 peak. | Not reported for the full cohort. Persistence around 6 mo | 9/21 (43%) patients No CAR T cells detected in relapsed patients. 5/9 patients had B-cell recovery. | 25% 12 mo PFS 30% 12 mo OS |
| Larson et al, 202373 UCLA, Los Angeles, California | 1 | Tandem CAR CD20 VL CD20 VH CD19 VH CD19 VL – 4-1BB | 10 (age 29-70 y) | MCL: 1 FL: 3 DLBCL: 1 tFL: 3 PM LBCL: 1 DH HGBCL: 1 | Refractory: 4 Previous autologous HSC: 1 Previous CAR-T: none Bridging: 9/10 (90%) | ORR: 9/10 (90%) CR: 7/10 (70%) At day 60 | Peak at 14 d | All responders remained in B-cell aplasia at time of data cutoff. 6 patients >12 mo B-cell aplasia | PD: 2/10 Relapse: 1/10 | 40% 18 mo PFS 70% 18 mo OS |
| Shah et al, 202074 Updated by Zurko et al75 in 2022 Milwaukee, Wisconsin | 1 | Tandem CAR CD20 – CD19 – 4-1BB 15 patients received fresh noncryopreserved products | 22 (age 38-72 y) | DLBCL: 11 MCL: 7 CLL: 3 FL: 1 | Previous autologous HSC: 8 Previous allogeneic HSCT: 3 Previous anti-CD19 CAR-T: 1 Bridging: 7/22 (32%) | ORR: 18/22 (82%) CR: 14/22 (64%) At day 28 | Higher expansion in patients with response. Peak at 7-12 d. | For patients with early CR, B-cell recovery was 42% at 6 mo and 56% at 9 mo. | PD: 8/22 Relapse: 5/22 All had biopsies and there was no CD19 or CD20 antigen loss. | Updated data for 16 patients who received target dose: 44% 24 mo PFS 69% 24 mo OS |
| Tong et al, 202076, extended by Zhang et al,77 Beijing, China | 1-2 | Tandem CAR (TanCAR7) CD20 VH CD20 VL CD19 VL CD19 VH – 4-1BB Fresh noncryopreserved product in all infusions. | 87 (age 16-70 y) | DLBCL: 58 FL: 13 tFL: 6 PMBCL: 5 CLL: 2 Small lymphocytic lymphoma: 2 MCL: 2 MALT: 1 | Previous autologous HSC: 12 Previous anti-CD19 CAR: 9 Bridging: none | ORR: 68/87 (78%) CR: 61/87 (70%) At month 3 | Peak 7-14 d. Higher levels in patients who achieved response. | Median around 100 d. Up to 400 d in 30 patients with ongoing CR. No difference in CAR T-cell levels between patients with ongoing response and relapse at days 21-40 and 41-60 | Relapse: 16/87 PD: 18/87 Biopsy available in 12 relapsed patients: −1 patient had CD19 and CD20 loss. −7 patients did not have detectable CAR T cells in tumor tissue or peripheral blood | Median PFS 27.6 mo 61% 12 mo PFS 79% 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 . |
|---|---|---|---|---|---|---|---|---|---|---|
| Sang et al, 202051 Xuzhou, China | 2 | Coadministration, same day
| 21 (age 23-72 y) | DLBCL: 21 | Refractoryv: 15 Previous autologous HSC: 1 Previous CAR-T: none Bridging: none | ORR: 17/21 (81%) CR: 11/21 (52%) At day 90 | Higher expansion in patients with response. No difference between CD19 and CD20 peak. | Not reported for the full cohort. Persistence around 6 mo | 9/21 (43%) patients No CAR T cells detected in relapsed patients. 5/9 patients had B-cell recovery. | 25% 12 mo PFS 30% 12 mo OS |
| Larson et al, 202373 UCLA, Los Angeles, California | 1 | Tandem CAR CD20 VL CD20 VH CD19 VH CD19 VL – 4-1BB | 10 (age 29-70 y) | MCL: 1 FL: 3 DLBCL: 1 tFL: 3 PM LBCL: 1 DH HGBCL: 1 | Refractory: 4 Previous autologous HSC: 1 Previous CAR-T: none Bridging: 9/10 (90%) | ORR: 9/10 (90%) CR: 7/10 (70%) At day 60 | Peak at 14 d | All responders remained in B-cell aplasia at time of data cutoff. 6 patients >12 mo B-cell aplasia | PD: 2/10 Relapse: 1/10 | 40% 18 mo PFS 70% 18 mo OS |
| Shah et al, 202074 Updated by Zurko et al75 in 2022 Milwaukee, Wisconsin | 1 | Tandem CAR CD20 – CD19 – 4-1BB 15 patients received fresh noncryopreserved products | 22 (age 38-72 y) | DLBCL: 11 MCL: 7 CLL: 3 FL: 1 | Previous autologous HSC: 8 Previous allogeneic HSCT: 3 Previous anti-CD19 CAR-T: 1 Bridging: 7/22 (32%) | ORR: 18/22 (82%) CR: 14/22 (64%) At day 28 | Higher expansion in patients with response. Peak at 7-12 d. | For patients with early CR, B-cell recovery was 42% at 6 mo and 56% at 9 mo. | PD: 8/22 Relapse: 5/22 All had biopsies and there was no CD19 or CD20 antigen loss. | Updated data for 16 patients who received target dose: 44% 24 mo PFS 69% 24 mo OS |
| Tong et al, 202076, extended by Zhang et al,77 Beijing, China | 1-2 | Tandem CAR (TanCAR7) CD20 VH CD20 VL CD19 VL CD19 VH – 4-1BB Fresh noncryopreserved product in all infusions. | 87 (age 16-70 y) | DLBCL: 58 FL: 13 tFL: 6 PMBCL: 5 CLL: 2 Small lymphocytic lymphoma: 2 MCL: 2 MALT: 1 | Previous autologous HSC: 12 Previous anti-CD19 CAR: 9 Bridging: none | ORR: 68/87 (78%) CR: 61/87 (70%) At month 3 | Peak 7-14 d. Higher levels in patients who achieved response. | Median around 100 d. Up to 400 d in 30 patients with ongoing CR. No difference in CAR T-cell levels between patients with ongoing response and relapse at days 21-40 and 41-60 | Relapse: 16/87 PD: 18/87 Biopsy available in 12 relapsed patients: −1 patient had CD19 and CD20 loss. −7 patients did not have detectable CAR T cells in tumor tissue or peripheral blood | Median PFS 27.6 mo 61% 12 mo PFS 79% 12 mo OS |
CLL, chronic lymphocytic leukemia; CR, complete remission; DH HGBCL, double-hit high-grade B-cell lymphoma; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; HSC, hematopoietic stem cell; HSCT, hematopoietic stem cell transplantation; MALT, mucosa-associated lymphoid tissue lymphoma; MCL, mantle cell lymphoma; 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; tFL, transformed follicular lymphoma; UCLA, University of California, Los Angeles; VH, variable heavy chain; VL, variable light chain.
Showing number of final infused patients.