EBV-associated lymphoproliferative disease post-CAR-T cell therapy

Abstract

Epstein–Barr virus (EBV)-associated lymphoproliferative diseases (EBV-LPDs) are common complications that occur after solid organ transplantation or allogeneic hematopoietic stem-cell transplantation (HSCT). However, their occurrence and treatment post-chimeric antigen receptor-modified T (CAR-T) cell therapy has not been reported. Two patients had been diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment. After receiving CAR-T cell therapy in tandem with autologous HSCT, the patients achieved complete remission. However, with a median time of 38.5 months after CAR-T cell therapy, B-cell-derived EBV-LPDs were diagnosed, and they were relieved through the administration of immune checkpoint inhibitor or B-cell-depleting agents. Collectively, our report suggests that EBV-LPDs may represent a long-term adverse event after CAR-T cell therapy, especially in patients who previously had EBV-positive disorders, and they can be resolved by immune normalization strategy or B-cell depleting therapy.

Keywords

EBV-associated lymphoproliferative disease / chimeric antigen receptor T-cell / autologous stem cell transplantation / immune checkpoint inhibitor

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Acknowledgements

We thank all the faculty and staff in the Clinical and Laboratory Unit of the Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology for their clinical and technical supports. We also thank Wuhan Human Genetic Resource Bank (Wuhan Biobank Co., Ltd.) for the support on sample storage and detection and data analysis. This work is supported by the funding from the National Natural Science Foundation of China (No. 82070211 to Dr. Liang Huang) and the National Key R&D Program of China (No. 2022YFC2502604 to Dr. Liang Huang).

Compliance with ethics guidelines

Conflicts of interest Shiyuan Zhang, Xiaoxi Zhou, Shangkun Zhang, Na Wang, Tongcun Zhang, Donghua Zhang, Qilin Ao, Yang Cao, and Liang Huang declare that they have no conflict of interest.

All the data used in this study were derived from existing deidentified biological samples and data from prior studies.

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