Table 5.
Clinical study outcomes of CAR-T cell therapy for tumors of the lymphohematopoietic system involving the CNS
| Disease type | Target | Product Types | Center | Partici-pants | Time | Authors | Research Institution | Clinical outcomes | Adverse events |
|---|---|---|---|---|---|---|---|---|---|
| SCNSL | CD19 | tisa-cel | singlecenter | 8 | 2019 | Frigault MJ, et al [173] | Massachusetts General Hospital Cancer Center, USA | 1 month: CR:25%,PR:25%,PD:50% | >1 ICANS:0 |
| SCNSL | CD19 | axi-cel, tisa-cel | singlecenter | 7 | 2021 | Ahmed G, et al [175] | Medical College of Wisconsin, USA |
At day 28: CR:85.7%,PD:14.3%; The median PFS:83 days(28–219); The median OS:129 days(32–219) |
no ICANS:3 patients; 1 or 3 ICANS:2 patients |
| PCNSL | CD19 | investigational product | singlecenter | 5 | 2021 | Siddiqi T, et al [169] | City of Hope Medical Center, USA | CR:60%,SD:40% |
1 CRS:100%; 1 ICANS:100% |
| PCNSL | CD19 | axi-cel, tisa-cel | multicenter | 9 | 2022 | Alcantara M, et al [176] | PSL Research University, France |
1 month: ORR:66.7%,CR:33.3%; 3 months: ORR:66.7%;CR:55.6%; 6 months: OS:89%,PFS:44%,DoR:67%; The median PFS:122 days |
CRS:7 patients; ICANS:5 patients |
| PCNSL | CD19 | tisa-cel | singlecenter | 12 | 2022 | Frigault MJ, et al [177] | Massachusetts General Hospital and Harvard Medical School, USA | ORR:58.3%,CR:50% |
CRS:58.3%; ICANS:41.6% |
| SCNSL | CD19 | investigational product | singlecenter | 10 | 2022 | Karschnia P, et al [174] | University Hospital, LMU, Germany |
1 month disease response:70%; The median PFS:7 months |
ICANS:60% |
| PCNSL/SCNSL | CD19 | axi-cel, tisa-cel | singlecenter | 21 | 2023 | Lacan C, et al [178] | PitiéSalpêtrière Hospital, France |
Persistent response:38%(6 CR 2 PR); The median OS in PCNSL:15 months; The median PFS:3 months |
CRS:16(1 grade 3); ICANS:7(2 grade ≥ 3) |
| SCNSL | CD19 | investigational product | multicenter | 10 | 2023 | Ryan CE, et al [170] | Dana-Farber Cancer Institute, USA |
ORR in the CNS:86%; 1 year PFS:47% |
CRS:90%; ICANS:70% |
| PCNSL/SCNSL | CD19 |
tisa-cel, axi-cel, liso-cel |
singlecenter | 44 | 2023 | Karschnia P, et al [190] | Harvard Medical School, USA | ORR:68.9%;CR:40.0% |
ICANS: In PCNSL:44.4%; In SCNSL:66.7% |
| SCNSL | CD19 | axi-cel, tisa-cel | multicenter | 28 | 2023 | Ayuk F, et al [171] | University Medical Center Hamburg-Eppendorf, Germany |
CR:32%;PR:32%;SD:11%;PD:25%The median OS:21 months; The median PFS:3.8 months |
CRS:86%; ICANS:46% |
| PCNSL | CD19 | axi-cel, tisa-cel | multicenter | 25 | 2024 | Choquet S, et al [179] | Hôpital Pitié-Salpêtrière, France |
The best response:64%; 1 year relapse-free survival:79%; The median OS:21.2 months; |
CRS:92%; ICANS:68% |
| MCL with SCNS involvement | CD19 | Brexu-cel, investigational product | multicenter | 12 | 2024 | Ahmed G, et al [180] | Medical College of Wisconsin, USA |
CNS response: 1 month: CR:92%;PR:8%; 3 months: CR:92%:PD:8%; 6 months PFS:50%;OS:75%; 12 monthsPFS:25%;OS:63%; incidence of relapse:50% |
1–2 CRS:91.67%; ICANS:83.33%(3–4 ICANS:58%) |
| SCNSL | CD19 |
tisa-cel, axi-cel, liso-cel |
multicenter | 113 | 2024 | Alsouqi A, et al [181] | University of Pittsburgh Medical Center, USA |
1 month ORR:68%,CR:34%; subgroup of patients with active SCNSL: The median PFS :2.9 months; The median OS:8.6 months |
CRS:75%; ICANS:56% |
| PCNSL/SCNSL | CD19 | relma-cel | multicenter | 22 | 2024 | Yu W, et al [182] | Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China |
the best ORR:90.9%; BCR rate:68.2%; the estimated 1-year PFS:64.4%;DOR:71.5%;OS:79.2% |
CRS:72.9%; ICANS:36.4% |
| PCNSL/SCNSL | CD19/CD20 | investigational product | singlecenter | 7 | 2022 | Shumilov E, et al [183] | The Third Xiangya Hospital of Central South University, China |
CR:4 patients; PR:3 patients; The median duration of CR:22.4 months |
1 CRS:71.43%, 2 CRS:28.57%; None ICANS; Hematological toxicities:71.43% |
| SCNSL |
CD19 CD20 CD22 |
investigational product | multicenter | 15 | 2022 | Zhang H, et al [191] | The Affiliated Hospital of Xuzhou Medical University, China |
ORR:73.3%;CR:60%;PR:13.3%; The median OS:9 months; The median PFS:4 months |
1–2 CRS:73.3%; ICANS:20% |
| PCNSL/SCNSL |
CD19 CD22 |
investigational product | singlecenter | 13 | 2021 | Wu J, et al [184] | Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China |
ORR:81.81%; CR:54.55%; 1 year PFS:74.59%; 1 year OS: 82.50% |
3–4 CRS:0; ICANS:1 patients |
| B-ALL | CD19 | investigational product | singlecenter | 12 | 2021 | Tan Y, et al [189] | Beijing Boren Hospital, China |
a month: CR:91.7%; Sustained remission:75%; 6-months LFS:81.8%; |
3–4 ICANS:33.3% |
| B-ALL | CD19 | investigational product | multicenter | 48 | 2022 | Qi Y, et al [188] | Xuzhou Medical University, China |
ORR:85.8%; The median EFS:8.7 months; The median OS:16 months |
3 CRS:18.8%; 3–4 ICANS:22.9% |
SCNSL Secondary central nervous system lymphoma, PCNSL Primary central nervous system lymphoma, CR Complete response, PR Partial response, PD Progressive disease, CRS Cytokine release syndrome, ICANS Immune effector cell-associated neurotoxicity syndrome, PFS Progression-free survival, OS Overall survival, SD Stable disease, ORR Overall response rate, DoR Duration of response