Evidence map›Paper›PMID 30528964›Full record

ReviewBlood reviews2019

Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management.

Jennifer N Brudno, James N Kochenderfer

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Blood reviews, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 535 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
535citing papers in PubMed, 10 pooled it
29.6field-weighted citation impact, top 1% of its field
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

535 citing papers in PubMed, 10 syntheses or guidelines pooled it, 890 citations in OpenAlex.

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  8. A systematic review of immunotherapy in high-grade glioma: learning from the past to shape future perspectives.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
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475 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

2 authors at 1 institution in 1 country.

Jennifer N BrudnoExperimental Transplantation and Immunology Branch, National Cancer Institute, Building 10, Suite 3-3330, Bethesda, MD 20892, United States. Electronic address: Jennifer.brudno@nih.gov.
James N KochenderferExperimental Transplantation and Immunology Branch, National Cancer Institute, Building 10, Suite 3-3330, Bethesda, MD 20892, United States. Electronic address: kochendj@mail.nih.gov.
National Cancer Institute · US

Funding

New Chimeric Antigen Receptors for Treating Hematologic MalignanciesZIABC011417 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KOCHENDERFER, JAMES · 2011 to 2025
$8.3M
Intramural NIH HHS Z99 CA999999
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T-cell therapy is an effective new treatment for hematologic malignancies. Two CAR T-cell products are now approved for clinical use by the U.S. FDA: tisagenlecleucel for pediatric acute lymphoblastic leukemia (ALL) and adult diffuse large B-cell lymphoma subtypes (DLBCL), and axicabtagene ciloleucel for DLBCL. CAR T-cell therapies are being developed for multiple myeloma, and clear evidence of clinical activity has been generated. A barrier to widespread use of CAR T-cell therapy is toxicity, primarily cytokine release syndrome (CRS) and neurologic toxicity. Manifestations of CRS include fevers, hypotension, hypoxia, end organ dysfunction, cytopenias, coagulopathy, and hemophagocytic lymphohistiocytosis. Neurologic toxicities are diverse and include encephalopathy, cognitive defects, dysphasias, seizures, and cerebral edema. Our understanding of the pathophysiology of CRS and neurotoxicity is continually improving. Early and peak levels of certain cytokines, peak blood CAR T-cell levels, patient disease burden, conditioning chemotherapy, CAR T-cell dose, endothelial activation, and CAR design are all factors that may influence toxicity. Multiple grading systems for CAR T-cell toxicity are in use; a universal grading system is needed so that CAR T-cell products can be compared across studies. Guidelines for toxicity management vary among centers, but typically include supportive care, plus immunosuppression with tocilizumab or corticosteroids administered for severe toxicity. Gaining a better understanding of CAR T-cell toxicities and developing new therapies for these toxicities are active areas of laboratory research. Further clinical investigation of CAR T-cell toxicity is also needed. In this review, we present guidelines for management of CRS and CAR neurotoxicity.

Indexed as

Cytotoxicity, ImmunologicAnimalsDisease ManagementHematologic NeoplasmsHumansImmunotherapy, AdoptiveReceptors, Antigen, T-CellReceptors, Chimeric AntigenRisk FactorsT-LymphocytesReceptors, Antigen, T-CellReceptors, Chimeric AntigenChimeric antigen receptor (CAR) T cellsHematologic malignanciesToxicity

Identifiers

PMID30528964
PMCPMC6628697
OpenAlexW2901262057

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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 OpenQuestion graph.