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

in Frontiers of medicine by Shiyuan Zhang, Xiaoxi Zhou, Shangkun Zhang, Na Wang, Tongcun Zhang, Donghua Zhang, Qilin Ao, Yang Cao, Liang Huang

TLDR

  • The study looked at two patients who had a type of cancer called Epstein-Barr virus (EBV)-associated lymphoproliferative diseases (EBV-LPDs) after receiving a treatment called chimeric antigen receptor-modified T (CAR-T) cell therapy. The patients had previously received other treatments for their cancer, but they relapsed. 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. The study 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.

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.

Overview

  • The study focuses on the occurrence and treatment of Epstein-Barr virus (EBV)-associated lymphoproliferative diseases (EBV-LPDs) after chimeric antigen receptor-modified T (CAR-T) cell therapy in solid organ transplantation or allogeneic hematopoietic stem-cell transplantation (HSCT) patients. The study uses a case series of two patients who were diagnosed with EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment. The patients received CAR-T cell therapy in tandem with autologous HSCT and 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. The primary objective of the study is to investigate the occurrence and treatment of EBV-LPDs after CAR-T cell therapy in patients with EBV-positive disorders and to suggest potential long-term adverse events and treatment strategies.

Comparative Analysis & Findings

  • The study compares the outcomes observed in two patients who received CAR-T cell therapy for EBV-positive aggressive B-cell lymphoma and experienced relapses after multiple lines of treatment. The patients achieved complete remission after CAR-T cell therapy in tandem with autologous HSCT. 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. The study identifies B-cell-derived EBV-LPDs as a long-term adverse event after CAR-T cell therapy, especially in patients who previously had EBV-positive disorders. The study suggests that immune normalization strategy or B-cell depleting therapy can be effective in resolving B-cell-derived EBV-LPDs.

Implications and Future Directions

  • The study's findings have significant implications for the field of research and clinical practice. The study 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. The study suggests that immune normalization strategy or B-cell depleting therapy can be effective in resolving B-cell-derived EBV-LPDs. The study highlights the need for further research to investigate the long-term safety and efficacy of CAR-T cell therapy in patients with EBV-positive disorders. The study suggests that future research should focus on developing novel immune normalization strategies or B-cell depleting therapies to prevent or treat EBV-LPDs after CAR-T cell therapy.