Effectiveness and safety of CD22 and CD19 dual-targeting chimeric antigen receptor T-cell therapy in patients with relapsed or refractory B-cell malignancies: A meta-analysis

Thi Thuy Nguyen; Nguyen Thanh Nhu; Chia-Ling Chen; Chiou-Feng Lin

doi:10.1002/cam4.6497

Effectiveness and safety of CD22 and CD19 dual-targeting chimeric antigen receptor T-cell therapy in patients with relapsed or refractory B-cell malignancies: A meta-analysis

Cancer Med. 2023 Sep;12(18):18767-18785. doi: 10.1002/cam4.6497. Epub 2023 Sep 5.

Authors

Thi Thuy Nguyen^{1

2

3}, Nguyen Thanh Nhu^{1

4}, Chia-Ling Chen⁵, Chiou-Feng Lin^{3

6

7}

Affiliations

¹ International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
² Department of Oncology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam.
³ Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁴ Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Vietnam.
⁵ School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁶ Core Laboratory of Immune Monitoring, Office of Research & Development, Taipei Medical University, Taipei, Taiwan.
⁷ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Abstract

Background: The efficacy of CD22 or CD19 chimeric antigen receptor T (CAR-T) cells in the management of acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL) was observed. Because antigen loss and lack of CAR-T-cell persistence are the leading causes of progressive disease following single-antigen targeting, we evaluated CD22/CD19 dual-targeting CAR-T-cell therapy efficacy and safety in relapsed/refractory B-cell malignancies.

Methods: The Web of Science, PubMed, Cochrane, and Embase databases were searched until July 2022. Patients confirmed with any relapsed/refractory B-cell hematological malignancies were included regardless of age, gender, or ethnicity, receiving CD22 and CD19-dual-targeting CAR-T-cell therapy. The studies conducted on patients with coexisting other cancer were excluded. We used random-effect models to explore the outcome, and heterogeneity was investigated by subgroup analysis.

Results: Fourteen studies (405 patients) were included. The pooled overall response (OR) and complete remission (CR) were 97% and 93%, respectively, for ALL patients. The 1-year proportions of overall survival (OS) and progression-free survival (PFS) were 70% and 49%, respectively. For NHL, OR occurred in 85% of patients, and 57% experienced CR. The results illustrated that the 1-year OS and 1-year PFS were 77% and 65%, respectively. The subgroup analysis showed that the dual-targeting modality achieved higher CR in the following cases: coadministration of CD22/CD19-CAR-T cells and third-generation CAR-T cells combined with ASCT and BEAM pretreatment. The ALL and NHL groups seemed similar in treatment-related toxicity: all grade cytokine release syndrome (CRS), severe CRS, and neurotoxicity occurred in 86%, 7%, and 12% of patients, respectively.

Conclusions: Our meta-analysis demonstrated that the CD22/CD19 dual-targeting CAR-T-cell strategy has high efficiency with tolerable adverse effects in B-cell malignancies.

Keywords: B cell malignancies; chimeric antigen receptor T (CAR-T) therapy; dual-targeting; efficacy; safety.

Abstract

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