Late Complications After European Medicines Agency-Approved Chimeric Antigen Receptor T-Cell Therapy in Hematological Malignancies: A Scoping Review

Chimeric antigen receptor T-cell (CAR-T) therapy has substantially improved outcomes for patients with B-cell-associated hematological malignancies. While acute and early toxicities are well characterized, late complications (LCs) remain poorly understood. This scoping review aimed to identify and map the existing evidence on LCs in adult patients with hematological malignancies treated with CAR-T products approved by the European Medicines Agency (EMA). PubMed, Web of Science, and the Cochrane Library were searched for primary studies published from 2018 onwards. We included studies of adult patients receiving EMA-approved CAR-T therapies targeting CD19 or CD269. LCs were defined as diagnosis-based adverse events occurring ≥12 months after CAR-T infusion. Of 7715 records identified, 261 studies underwent full-text screening and 18 met the inclusion criteria. LCs clustered mainly as infections and secondary malignancies (SMs). Non-relapse mortality was reported in seven studies, with infections and SMs frequently reported as causes when cause-of-death data were available. Future studies should place emphasis on long-term clinical events after CAR-T therapy to improve the management of LCs and ultimately support better long-term outcomes for patients.