A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells
Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been FDA-approved, CAR T-cells targeting CD22, as well as dual-targeting CD19/CD22 CAR T-cells, are currently being evaluated in clinical trials....
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| Format: | Article |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1178403/full |
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| author | Nathan J. Fergusson Nathan J. Fergusson Komal Adeel Natasha Kekre Natasha Kekre Natasha Kekre Harold Atkins Harold Atkins Kevin A. Hay Kevin A. Hay Kevin A. Hay |
| author_facet | Nathan J. Fergusson Nathan J. Fergusson Komal Adeel Natasha Kekre Natasha Kekre Natasha Kekre Harold Atkins Harold Atkins Kevin A. Hay Kevin A. Hay Kevin A. Hay |
| author_sort | Nathan J. Fergusson |
| collection | DOAJ |
| description | Chimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been FDA-approved, CAR T-cells targeting CD22, as well as dual-targeting CD19/CD22 CAR T-cells, are currently being evaluated in clinical trials. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CD22-targeting CAR T-cell therapies. We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to March 3rd 2022 for full-length articles and conference abstracts of clinical trials employing CD22-targeting CAR T-cells in acute lymphocytic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL). The primary outcome was best complete response (bCR). A DerSimonian and Laird random-effects model with arcsine transformation was used to pool outcome proportions. From 1068 references screened, 100 were included, representing 30 early phase studies with 637 patients, investigating CD22 or CD19/CD22 CAR T-cells. CD22 CAR T-cells had a bCR of 68% [95% CI, 53-81%] in ALL (n= 116), and 64% [95% CI, 46-81%] in NHL (n= 28) with 74% and 96% of patients having received anti-CD19 CAR T-cells previously in ALL and NHL studies respectively. CD19/CD22 CAR T-cells had a bCR rate of 90% [95% CI, 84-95%] in ALL (n= 297) and 47% [95% CI, 34-61%] in NHL (n= 137). The estimated incidence of total and severe (grade ≥3) CRS were 87% [95% CI, 80-92%] and 6% [95% CI, 3-9%] respectively. ICANS and severe ICANS had an estimated incidence of 16% [95% CI, 9-25%] and 3% [95% CI, 1-5%] respectively. Early phase trials of CD22 and CD19/CD22 CAR T-cells show high remission rates in ALL and NHL. Severe CRS or ICANS were (1)rare and dual-targeting did not increase toxicity. Variability in CAR construct, dose, and patient factors amongst studies limits comparisons, with long-term outcomes yet to be reported.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42020193027. |
| first_indexed | 2024-04-09T15:44:44Z |
| format | Article |
| id | doaj.art-e7e328e2355f43348796f7b3acd4eeaa |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T15:44:44Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e7e328e2355f43348796f7b3acd4eeaa2023-04-27T04:53:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11784031178403A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cellsNathan J. Fergusson0Nathan J. Fergusson1Komal Adeel2Natasha Kekre3Natasha Kekre4Natasha Kekre5Harold Atkins6Harold Atkins7Kevin A. Hay8Kevin A. Hay9Kevin A. Hay10Department of Medicine, University of Toronto, Toronto, ON, CanadaClinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, CanadaFaculty of Medicine, University of British Columbia, Vancouver, BC, CanadaClinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, CanadaSchool of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, CanadaDivision of Hematology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, CanadaClinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, CanadaDivision of Hematology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, CanadaFaculty of Medicine, University of British Columbia, Vancouver, BC, CanadaTerry Fox Laboratory, BC Cancer Research Institute, Vancouver, BC, CanadaVancouver General Hospital, Leukemia and Bone Marrow Transplant Program of British Columbia, Vancouver, BC, CanadaChimeric antigen receptor (CAR) T-cells are an emerging therapy for the treatment of relapsed/refractory B-cell malignancies. While CD19 CAR-T cells have been FDA-approved, CAR T-cells targeting CD22, as well as dual-targeting CD19/CD22 CAR T-cells, are currently being evaluated in clinical trials. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CD22-targeting CAR T-cell therapies. We searched MEDLINE, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials from inception to March 3rd 2022 for full-length articles and conference abstracts of clinical trials employing CD22-targeting CAR T-cells in acute lymphocytic leukemia (ALL) and non-Hodgkin’s lymphoma (NHL). The primary outcome was best complete response (bCR). A DerSimonian and Laird random-effects model with arcsine transformation was used to pool outcome proportions. From 1068 references screened, 100 were included, representing 30 early phase studies with 637 patients, investigating CD22 or CD19/CD22 CAR T-cells. CD22 CAR T-cells had a bCR of 68% [95% CI, 53-81%] in ALL (n= 116), and 64% [95% CI, 46-81%] in NHL (n= 28) with 74% and 96% of patients having received anti-CD19 CAR T-cells previously in ALL and NHL studies respectively. CD19/CD22 CAR T-cells had a bCR rate of 90% [95% CI, 84-95%] in ALL (n= 297) and 47% [95% CI, 34-61%] in NHL (n= 137). The estimated incidence of total and severe (grade ≥3) CRS were 87% [95% CI, 80-92%] and 6% [95% CI, 3-9%] respectively. ICANS and severe ICANS had an estimated incidence of 16% [95% CI, 9-25%] and 3% [95% CI, 1-5%] respectively. Early phase trials of CD22 and CD19/CD22 CAR T-cells show high remission rates in ALL and NHL. Severe CRS or ICANS were (1)rare and dual-targeting did not increase toxicity. Variability in CAR construct, dose, and patient factors amongst studies limits comparisons, with long-term outcomes yet to be reported.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42020193027.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1178403/fullCAR T-cellCD22B-cell malignanciesefficacysafetysystematic review & meta-analysis |
| spellingShingle | Nathan J. Fergusson Nathan J. Fergusson Komal Adeel Natasha Kekre Natasha Kekre Natasha Kekre Harold Atkins Harold Atkins Kevin A. Hay Kevin A. Hay Kevin A. Hay A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells Frontiers in Immunology CAR T-cell CD22 B-cell malignancies efficacy safety systematic review & meta-analysis |
| title | A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells |
| title_full | A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells |
| title_fullStr | A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells |
| title_full_unstemmed | A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells |
| title_short | A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells |
| title_sort | systematic review and meta analysis of cd22 car t cells alone or in combination with cd19 car t cells |
| topic | CAR T-cell CD22 B-cell malignancies efficacy safety systematic review & meta-analysis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1178403/full |
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