A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy Review
| Authors: | Cordas dos Santos, D. M.; Tix, T.; Shouval, R.; Gafter-Gvili, A.; Alberge, J. B.; Cliff, E. R. S.; Theurich, S.; von Bergwelt-Baildon, M.; Ghobrial, I. M.; Subklewe, M.; Perales, M. A.; Rejeski, K. |
| Review Title: | A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy |
| 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. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024. |
| Keywords: | adult; mortality; neurotoxicity; mantle cell lymphoma; multiple myeloma; bleeding; cancer mortality; lung embolism; cause of death; immunology; myelodysplastic syndrome; systematic review; cardiovascular disease; thromboembolism; lymphoma; carcinoma; chimeric antigen receptor; medline; virus infection; second cancer; cochrane library; brain ischemia; bacterial infection; mycosis; therapy; meta analysis; adoptive immunotherapy; immunotherapy, adoptive; biological product; biological products; heart arrest; cerebrovascular accident; cardiomyopathy; respiratory tract disease; respiratory failure; embase; hemophagocytic syndrome; adverse event; phase 2 clinical trial (topic); phase 3 clinical trial (topic); phase 1 clinical trial (topic); clinical outcome; cytokine release syndrome; acute myeloid leukemia; procedures; diffuse large b cell lymphoma; ischemic colitis; humans; human; article; tisagenlecleucel t; chimeric antigen receptor t-cell immunotherapy; axicabtagene ciloleucel; lisocabtagene maraleucel; aortic dissection; coronavirus disease 2019; immune effector cell associated neurotoxicity syndrome; receptors, chimeric antigen; cell therapy agent; brexucabtagene autoleucel; ciltacabtagene autoleucel; idecabtagene vicleucel; indolent b cell non hodgkin lymphoma |
| Journal Title: | Nature Medicine |
| Volume: | 30 |
| Issue: | 9 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-09-01 |
| Start Page: | 2667 |
| End Page: | 2678 |
| Language: | English |
| DOI: | 10.1038/s41591-024-03084-6 |
| PUBMED: | 38977912 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is Kai Rejeski -- MSK author S. Giralt thanked in the acknowledgments -- Source: Scopus |
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