Emerging T-cell lymphomas after CAR T-cell therapy

Abstract

Chimeric antigen receptor (CAR) T-cell therapies have transformed the treatment landscape for relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL) and multiple myeloma (MM), delivering unprecedented response rates even in heavily pretreated patients [ 1 , 2 ]. However, their remarkable efficacy does not come without risks. While acute toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are well-documented, a new and alarming concern has emerged. In November 2023, the U.S. Food and Drug Administration (FDA) reported 22 cases of T-cell malignancies in patients treated with CAR-T cell therapy [ 3 ], placing secondary T-cell lymphoma on the growing list of potential complications of CAR-T cell therapy. Of particular concern are cases of CAR-expressing T-cell lymphomas, raising urgent questions about whether vector integration events during CAR-T cell manufacturing disrupt gene expression and contribute to malignant transformation. In this perspective, we integrate the latest evidence on CAR+ T-cell lymphomas, dissect their diagnostic as well as clinical features, and explore the molecular mechanisms that may drive their emergence. We further discuss the potential clinical implications of these findings and strategies to mitigate this emerging risk.

Topics & Concepts