A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy

David M. Cordas dos Santos, Tobias Tix, Roni Shouval, Anat Gafter-Gvili, Jean Baptiste Alberge, Edward R.Scheffer Cliff, Sebastian Theurich, Michael von Bergwelt-Baildon, Irene M. Ghobrial, Marion Subklewe, Miguel Angel Perales, Kai Rejeski

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Although chimeric antigen receptor (CAR) T cell therapy represents a transformative immunotherapy, it is also associated with distinct toxicities that contribute to morbidity and mortality. In this systematic review and meta-analysis, we searched MEDLINE, Embase and CINAHL (Cochrane) for reports of nonrelapse mortality (NRM) after CAR T cell therapy in lymphoma and multiple myeloma up to March 2024. After extraction of causes and numbers of death, we analyzed NRM point estimates using random-effect models. We identified 7,604 patients across 18 clinical trials and 28 real-world studies. NRM point estimates varied across disease entities and were highest in patients with mantle-cell lymphoma (10.6%), followed by multiple myeloma (8.0%), large B cell lymphoma (6.1%) and indolent lymphoma (5.7%). Entity-specific meta-regression models for large B cell lymphoma and multiple myeloma revealed that axicabtagene ciloleucel and ciltacabtagene autoleucel were independently associated with increased NRM point estimates, respectively. Of 574 reported nonrelapse deaths, over half were attributed to infections (50.9%), followed by other malignancies (7.8%) and cardiovascular/respiratory events (7.3%). Conversely, the CAR T cell-specific side effects, immune effector cell-associated neurotoxicity syndrome/neurotoxicity, cytokine release syndrome and hemophagocytic lymphohistiocytosis, represented only a minority of nonrelapse deaths (cumulatively 11.5%). Our findings underline the critical importance of infectious complications after CAR T cell therapy and support the comprehensive reporting of NRM, including specific causes and long-term outcomes.

Original languageEnglish
Pages (from-to)2667-2678
Number of pages12
JournalNature Medicine
Volume30
Issue number9
Early online date8 Jul 2024
DOIs
StatePublished - Sep 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.

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