A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells

Nathan J Fergusson; Komal Adeel; Natasha Kekre; Harold Atkins; Kevin A Hay

doi:10.3389/fimmu.2023.1178403

A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells

Front Immunol. 2023 Apr 27:14:1178403. doi: 10.3389/fimmu.2023.1178403. eCollection 2023.

Authors

Nathan J Fergusson^{1

2}, Komal Adeel³, Natasha Kekre^{2

4

5}, Harold Atkins^{2

5}, Kevin A Hay^{3

6

7}

Affiliations

¹ Department of Medicine, University of Toronto, Toronto, ON, Canada.
² Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
³ Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
⁴ School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
⁵ Division of Hematology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada.
⁶ Terry Fox Laboratory, BC Cancer Research Institute, Vancouver, BC, Canada.
⁷ Vancouver General Hospital, Leukemia and Bone Marrow Transplant Program of British Columbia, Vancouver, BC, Canada.

Abstract

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 registration: https://www.crd.york.ac.uk/prospero, identifier CRD42020193027.

Keywords: B-cell malignancies; CAR T-cell; CD22; efficacy; safety; systematic review & meta-analysis.

Publication types

Meta-Analysis
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

B-Lymphocytes
Humans
Immunotherapy, Adoptive / adverse effects
Lymphoma, Non-Hodgkin* / therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
Recurrence
Sialic Acid Binding Ig-like Lectin 2
T-Lymphocytes

Substances

CD22 protein, human
Sialic Acid Binding Ig-like Lectin 2

Grants and funding

This project was funded in part by a grant from Biotherapeutics for Cancer Treatment (BioCanRx), a Canadian Network of Centers of Excellence (FY20/ES15). NF’s salary was supported by a summer studentship award from BioCanRx (Ref # FY20/SS10), payments made to HA affiliated institution. KA contributed as part of the FLEX Course at the UBC Medical Undergraduate Program.