Evidence map›Paper›PMID 38977912›Full record

SynthesisNature medicine2024

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 and 2 more

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
165citing papers in PubMed, 11 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

165 citing papers in PubMed, 11 syntheses or guidelines pooled it.

  1. Guideline
  2. Pooled it
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  10. Second Primary Malignancies after CAR T-Cell Therapy: A Systematic Review and Meta-analysis of 5,517 Lymphoma and Myeloma Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    Pooled it
  11. Guideline
  12. Trial
  13. Trial
  14. Trial
  15. Article
  16. Article
  17. Article
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  19. Review
  20. Article

105 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

David M Cordas Dos Santos *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Tobias Tix *Department of Medicine III-Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany.
Roni ShouvalAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Anat Gafter-GviliDepartment of Medicine A and Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel.ORCID http://orcid.org/0000-0003-1666-5114
Jean-Baptiste AlbergeDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Edward R Scheffer CliffDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5977-907X
Sebastian TheurichDepartment of Medicine III-Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany.ORCID http://orcid.org/0000-0001-5706-8258
Michael von Bergwelt-BaildonDepartment of Medicine III-Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany.
Irene M GhobrialDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7361-3092
Marion SubkleweDepartment of Medicine III-Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany.
Miguel-Angel PeralesAdult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-5910-4571
Kai RejeskiDepartment of Medicine III-Hematology/Oncology, LMU University Hospital, LMU Munich, Munich, Germany. rejeskik@mskcc.org.ORCID http://orcid.org/0000-0003-3905-0251

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI FRANCESCA M GANY · 1985 to 2026
$347.4M
A multimodal approach for precision immuno-oncology in lymphoma treated with CAR-T cellsK08CA282987 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Roni Shouval · 2023 to 2026
$1.1M
Deutsche Forschungsgemeinschaft (German Research Foundation) SFB-TRR 388/1 2021 - 452881907Deutsche Forschungsgemeinschaft (German Research Foundation) Walter-Benjamin FellowshipNCI NIH HHS K08 CA282987NCI NIH HHS P30 CA008748
6 · The paper itself

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.

Indexed as

Immunotherapy, AdoptiveLymphomaMultiple MyelomaBiological ProductsHumansReceptors, Chimeric Antigenaxicabtagene ciloleucelBiological ProductsReceptors, Chimeric Antigen

Identifiers

PMID38977912
PMCPMC11765209

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.