FDA Reports of Secondary Malignancies Following Chimeric Antigen Receptor (CAR) T Cell Therapies and Relative Risk: an EBMT-EHA-GoCART Coalition Statement

We need to bring your attention to the recent warning disseminated by the Food and Drug Administration (FDA) regarding T-cell lymphomas in patients undergoing Chimeric Antigen Receptor T-cell (CAR-T) therapy (1). Specifically, the FDA warning highlights the potential risks associated with CAR T-cell therapies regarding the development of T-cell lymphomas secondary to a mechanism of CAR-T transgene insertional mutagenesis.

While the warning emphasises necessary vigilance and meticulous monitoring during CAR T-cell therapy, at this stage the European Society for Blood and Marrow Transplantation (EBMT) and EHA support the FDA statement that the therapeutic benefits of CAR T-cell therapies outweigh their potential risks for the approved settings.

Nevertheless, certain key questions remain unanswered, including the precise role of transgene insertional mutagenesis in T-cell malignancy cases post-CART therapy, the current practice of re-typing lineage in secondary lymphoid malignancies for patients treated for B-cell lymphoma, and access to molecular analysis for detecting CAR-T transgenes in T-cell malignancies.

Given the scarcity of data, it is becoming crucial to confirm lymphoma subtypes through biopsy in suspected relapse cases, even when immediate therapeutic implications may not be evident.

In response to these evolving developments, the EBMT is committed to the ongoing evaluation of emerging data. We actively support research and audit initiatives, prioritising the safety and well-being of our patients. In the coming weeks, a specific EBMT Survey will be launched at centre level to collect relevant information related to secondary T-cell malignancies potentially linked to insertional mutagenesis.

The commitment of the EBMT community to collaborative efforts in advancing knowledge and improving patient outcomes is essential. We encourage healthcare professionals, scientists, and researchers to actively collaborate and share insights to enhance the knowledge base and refinement of haematopoietic cellular therapies.

Thank you for your ongoing support and commitment and for prioritising the health and safety of our patients.


(1) FDA Investigating Serious Risk of T-cell Malignancy Following BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies. 2023; Available from: https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-serious-risk-t-cell-malignancy-following-bcma-directed-or-cd19-directed-autologous

Last Updated on Wednesday 13 December 2023.