Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-12-03

AUTHORS

Gils Roex, Marijke Timmers, Kristien Wouters, Diana Campillo-Davo, Donovan Flumens, Wilfried Schroyens, Yiwei Chu, Zwi N. Berneman, Eva Lion, Feifei Luo, Sébastien Anguille

ABSTRACT

BackgroundB-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T-cell therapy is an emerging treatment option for multiple myeloma. The aim of this systematic review and meta-analysis was to determine its safety and clinical activity and to identify factors influencing these outcomes.MethodsWe performed a database search using the terms “BCMA,” “CAR,” and “multiple myeloma” for clinical studies published between 01/01/2015 and 01/01/2020. The methodology is further detailed in PROSPERO (CRD42020125332).ResultsTwenty-three different CAR-T-cell products have been used so far in 640 patients. Cytokine release syndrome was observed in 80.3% (69.0–88.2); 10.5% (6.8–16.0) had neurotoxicity. A higher neurotoxicity rate was reported in studies that included more heavily pretreated patients: 19.1% (13.3–26.7; I2 = 45%) versus 2.8% (1.3–6.1; I2 = 0%) (p < 0.0001). The pooled overall response rate was 80.5% (73.5–85.9); complete responses (CR) were observed in 44.8% (35.3–54.6). A pooled CR rate of 71.9% (62.8–79.6; I2 = 0%) was noted in studies using alpaca/llama-based constructs, whereas it was only 18.0% (6.5–41.1; I2 = 67%) in studies that used retroviral vectors for CAR transduction. Median progression-free survival (PFS) was 12.2 (11.4–17.4) months, which compared favorably to the expected PFS of 1.9 (1.5–3.7) months (HR 0.14; p < 0.0001).ConclusionsAlthough considerable toxicity was observed, BCMA-targeted CAR-T-cell therapy is highly efficacious even in advanced multiple myeloma. Subgroup analysis confirmed the anticipated inter-study heterogeneity and identified potential factors contributing to safety and efficacy. The results of this meta-analysis may assist the future design of CAR-T-cell studies and lead to optimized BCMA CAR-T-cell products. More... »

PAGES

164

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13045-020-01001-1

DOI

http://dx.doi.org/10.1186/s13045-020-01001-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1132951048

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33272302


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1103", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Clinical Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "B-Cell Maturation Antigen", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cytokine Release Syndrome", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Immunotherapy, Adoptive", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Multiple Myeloma", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Neurotoxicity Syndromes", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Progression-Free Survival", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Receptors, Chimeric Antigen", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Treatment Outcome", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium", 
          "id": "http://www.grid.ac/institutes/grid.5284.b", 
          "name": [
            "Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Roex", 
        "givenName": "Gils", 
        "id": "sg:person.010621545656.01", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010621545656.01"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Hematology and Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium", 
          "id": "http://www.grid.ac/institutes/grid.411414.5", 
          "name": [
            "Division of Hematology and Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Timmers", 
        "givenName": "Marijke", 
        "id": "sg:person.016565367053.55", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016565367053.55"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Clinical Trial Center, Antwerp University Hospital, Edegem, Belgium", 
          "id": "http://www.grid.ac/institutes/grid.411414.5", 
          "name": [
            "Clinical Trial Center, Antwerp University Hospital, Edegem, Belgium"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wouters", 
        "givenName": "Kristien", 
        "id": "sg:person.01352625767.77", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01352625767.77"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium", 
          "id": "http://www.grid.ac/institutes/grid.5284.b", 
          "name": [
            "Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Campillo-Davo", 
        "givenName": "Diana", 
        "id": "sg:person.010035360171.51", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010035360171.51"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium", 
          "id": "http://www.grid.ac/institutes/grid.5284.b", 
          "name": [
            "Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Flumens", 
        "givenName": "Donovan", 
        "id": "sg:person.012024353123.35", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012024353123.35"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Hematology and Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium", 
          "id": "http://www.grid.ac/institutes/grid.411414.5", 
          "name": [
            "Division of Hematology and Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Schroyens", 
        "givenName": "Wilfried", 
        "id": "sg:person.0653223122.50", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0653223122.50"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Biotherapy Research Center, Fudan University, Shanghai, China", 
          "id": "http://www.grid.ac/institutes/grid.8547.e", 
          "name": [
            "Biotherapy Research Center, Fudan University, Shanghai, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chu", 
        "givenName": "Yiwei", 
        "id": "sg:person.0716461200.52", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0716461200.52"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Hematology and Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium", 
          "id": "http://www.grid.ac/institutes/grid.411414.5", 
          "name": [
            "Division of Hematology and Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Berneman", 
        "givenName": "Zwi N.", 
        "id": "sg:person.0715102045.57", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0715102045.57"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium", 
          "id": "http://www.grid.ac/institutes/grid.5284.b", 
          "name": [
            "Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lion", 
        "givenName": "Eva", 
        "id": "sg:person.01104533052.91", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01104533052.91"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Digestive Diseases, Huashan Hospital of Fudan University, Shanghai, China", 
          "id": "http://www.grid.ac/institutes/grid.411405.5", 
          "name": [
            "Biotherapy Research Center, Fudan University, Shanghai, China", 
            "Department of Digestive Diseases, Huashan Hospital of Fudan University, Shanghai, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Luo", 
        "givenName": "Feifei", 
        "id": "sg:person.0660155350.49", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0660155350.49"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Hematology and Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium", 
          "id": "http://www.grid.ac/institutes/grid.411414.5", 
          "name": [
            "Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium", 
            "Division of Hematology and Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Anguille", 
        "givenName": "S\u00e9bastien", 
        "id": "sg:person.01341351131.75", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01341351131.75"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/s41586-019-1054-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1113006931", 
          "https://doi.org/10.1038/s41586-019-1054-1"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13045-018-0672-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1107776019", 
          "https://doi.org/10.1186/s13045-018-0672-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/s41591-018-0010-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1103686011", 
          "https://doi.org/10.1038/s41591-018-0010-1"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13045-018-0681-6", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1110812362", 
          "https://doi.org/10.1186/s13045-018-0681-6"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13045-018-0653-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1107214929", 
          "https://doi.org/10.1186/s13045-018-0653-x"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/s41467-019-14119-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1124098340", 
          "https://doi.org/10.1038/s41467-019-14119-9"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/s41375-019-0669-4", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1122956360", 
          "https://doi.org/10.1038/s41375-019-0669-4"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13045-020-00962-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1130921904", 
          "https://doi.org/10.1186/s13045-020-00962-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/s41375-020-0734-z", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1124844369", 
          "https://doi.org/10.1038/s41375-020-0734-z"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13045-019-0823-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1122783824", 
          "https://doi.org/10.1186/s13045-019-0823-5"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2020-12-03", 
    "datePublishedReg": "2020-12-03", 
    "description": "BackgroundB-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T-cell therapy is an emerging treatment option for multiple myeloma. The aim of this systematic review and meta-analysis was to determine its safety and clinical activity and to identify factors influencing these outcomes.MethodsWe performed a database search using the terms \u201cBCMA,\u201d \u201cCAR,\u201d and \u201cmultiple myeloma\u201d for clinical studies published between 01/01/2015 and 01/01/2020. The methodology is further detailed in PROSPERO (CRD42020125332).ResultsTwenty-three different CAR-T-cell products have been used so far in 640 patients. Cytokine release syndrome was observed in 80.3% (69.0\u201388.2); 10.5% (6.8\u201316.0) had neurotoxicity. A higher neurotoxicity rate was reported in studies that included more heavily pretreated patients: 19.1% (13.3\u201326.7; I2\u2009=\u200945%) versus 2.8% (1.3\u20136.1; I2\u2009=\u20090%) (p\u2009<\u20090.0001). The pooled overall response rate was 80.5% (73.5\u201385.9); complete responses (CR) were observed in 44.8% (35.3\u201354.6). A pooled CR rate of 71.9% (62.8\u201379.6; I2\u2009=\u20090%) was noted in studies using alpaca/llama-based constructs, whereas it was only 18.0% (6.5\u201341.1; I2\u2009=\u200967%) in studies that used retroviral vectors for CAR transduction. Median progression-free survival (PFS) was 12.2 (11.4\u201317.4) months, which compared favorably to the expected PFS of 1.9 (1.5\u20133.7) months (HR 0.14; p\u2009<\u20090.0001).ConclusionsAlthough considerable toxicity was observed, BCMA-targeted CAR-T-cell therapy is highly efficacious even in advanced multiple myeloma. Subgroup analysis confirmed the anticipated inter-study heterogeneity and identified potential factors contributing to safety and efficacy. The results of this meta-analysis may assist the future design of CAR-T-cell studies and lead to optimized BCMA CAR-T-cell products.", 
    "genre": "article", 
    "id": "sg:pub.10.1186/s13045-020-01001-1", 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1039771", 
        "issn": [
          "1756-8722"
        ], 
        "name": "Journal of Hematology & Oncology", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "13"
      }
    ], 
    "keywords": [
      "progression-free survival", 
      "CAR T-cell therapy", 
      "CAR T-cell products", 
      "multiple myeloma", 
      "complete response", 
      "BCMA-targeted CAR T-cell therapy", 
      "BCMA CAR T-cell therapy", 
      "pooled overall response rate", 
      "median progression-free survival", 
      "CAR T-cell studies", 
      "cytokine release syndrome", 
      "pooled CR rate", 
      "advanced multiple myeloma", 
      "T-cell therapy", 
      "overall response rate", 
      "chimeric antigen receptor", 
      "inter-study heterogeneity", 
      "neurotoxicity rates", 
      "CAR transduction", 
      "release syndrome", 
      "CR rate", 
      "clinical efficacy", 
      "treatment options", 
      "subgroup analysis", 
      "maturation antigen", 
      "clinical activity", 
      "clinical studies", 
      "response rate", 
      "myeloma", 
      "systematic review", 
      "considerable toxicity", 
      "antigen receptor", 
      "therapy", 
      "patients", 
      "months", 
      "database search", 
      "efficacy", 
      "potential factors", 
      "retroviral vectors", 
      "safety", 
      "syndrome", 
      "neurotoxicity", 
      "PROSPERO", 
      "study", 
      "antigen", 
      "MethodsWe", 
      "BCMA", 
      "receptors", 
      "survival", 
      "outcomes", 
      "rate", 
      "factors", 
      "toxicity", 
      "review", 
      "options", 
      "aim", 
      "response", 
      "activity", 
      "transduction", 
      "heterogeneity", 
      "search", 
      "analysis", 
      "results", 
      "constructs", 
      "products", 
      "future design", 
      "vector", 
      "terms", 
      "design", 
      "cars", 
      "methodology"
    ], 
    "name": "Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma", 
    "pagination": "164", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1132951048"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1186/s13045-020-01001-1"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "33272302"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1186/s13045-020-01001-1", 
      "https://app.dimensions.ai/details/publication/pub.1132951048"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-12-01T06:40", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20221201/entities/gbq_results/article/article_837.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1186/s13045-020-01001-1"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s13045-020-01001-1'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s13045-020-01001-1'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s13045-020-01001-1'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s13045-020-01001-1'


 

This table displays all metadata directly associated to this object as RDF triples.

290 TRIPLES      21 PREDICATES      115 URIs      97 LITERALS      16 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1186/s13045-020-01001-1 schema:about N0f1d1c25daca4c76810148204b624f8f
2 N3264e42fa685488eb6205a8e798ab9be
3 N408b9c0f192b4a24a0dcc1a1d0cdacb7
4 N73f6704f8739442d86ecffe004e2c7cc
5 N78de622a42d745e4b2341491c87bfd44
6 Nbdc9df91cb76457ba32abf30de89dddf
7 Ne53c37acf0604bbbb6fc188f1115132c
8 Ne549f6de877948f399fe78defbe5ebb4
9 Nf56c7588d6604d2ab1565c21057e36da
10 anzsrc-for:11
11 anzsrc-for:1103
12 schema:author N6ee003b9f04d4d4bbd87868a1aee68a4
13 schema:citation sg:pub.10.1038/s41375-019-0669-4
14 sg:pub.10.1038/s41375-020-0734-z
15 sg:pub.10.1038/s41467-019-14119-9
16 sg:pub.10.1038/s41586-019-1054-1
17 sg:pub.10.1038/s41591-018-0010-1
18 sg:pub.10.1186/s13045-018-0653-x
19 sg:pub.10.1186/s13045-018-0672-7
20 sg:pub.10.1186/s13045-018-0681-6
21 sg:pub.10.1186/s13045-019-0823-5
22 sg:pub.10.1186/s13045-020-00962-7
23 schema:datePublished 2020-12-03
24 schema:datePublishedReg 2020-12-03
25 schema:description BackgroundB-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T-cell therapy is an emerging treatment option for multiple myeloma. The aim of this systematic review and meta-analysis was to determine its safety and clinical activity and to identify factors influencing these outcomes.MethodsWe performed a database search using the terms “BCMA,” “CAR,” and “multiple myeloma” for clinical studies published between 01/01/2015 and 01/01/2020. The methodology is further detailed in PROSPERO (CRD42020125332).ResultsTwenty-three different CAR-T-cell products have been used so far in 640 patients. Cytokine release syndrome was observed in 80.3% (69.0–88.2); 10.5% (6.8–16.0) had neurotoxicity. A higher neurotoxicity rate was reported in studies that included more heavily pretreated patients: 19.1% (13.3–26.7; I2 = 45%) versus 2.8% (1.3–6.1; I2 = 0%) (p < 0.0001). The pooled overall response rate was 80.5% (73.5–85.9); complete responses (CR) were observed in 44.8% (35.3–54.6). A pooled CR rate of 71.9% (62.8–79.6; I2 = 0%) was noted in studies using alpaca/llama-based constructs, whereas it was only 18.0% (6.5–41.1; I2 = 67%) in studies that used retroviral vectors for CAR transduction. Median progression-free survival (PFS) was 12.2 (11.4–17.4) months, which compared favorably to the expected PFS of 1.9 (1.5–3.7) months (HR 0.14; p < 0.0001).ConclusionsAlthough considerable toxicity was observed, BCMA-targeted CAR-T-cell therapy is highly efficacious even in advanced multiple myeloma. Subgroup analysis confirmed the anticipated inter-study heterogeneity and identified potential factors contributing to safety and efficacy. The results of this meta-analysis may assist the future design of CAR-T-cell studies and lead to optimized BCMA CAR-T-cell products.
26 schema:genre article
27 schema:isAccessibleForFree true
28 schema:isPartOf N4c853d8bc1624608b749b404fec59f35
29 Nb6e963680dfc419abd97166461ac6abf
30 sg:journal.1039771
31 schema:keywords BCMA
32 BCMA CAR T-cell therapy
33 BCMA-targeted CAR T-cell therapy
34 CAR T-cell products
35 CAR T-cell studies
36 CAR T-cell therapy
37 CAR transduction
38 CR rate
39 MethodsWe
40 PROSPERO
41 T-cell therapy
42 activity
43 advanced multiple myeloma
44 aim
45 analysis
46 antigen
47 antigen receptor
48 cars
49 chimeric antigen receptor
50 clinical activity
51 clinical efficacy
52 clinical studies
53 complete response
54 considerable toxicity
55 constructs
56 cytokine release syndrome
57 database search
58 design
59 efficacy
60 factors
61 future design
62 heterogeneity
63 inter-study heterogeneity
64 maturation antigen
65 median progression-free survival
66 methodology
67 months
68 multiple myeloma
69 myeloma
70 neurotoxicity
71 neurotoxicity rates
72 options
73 outcomes
74 overall response rate
75 patients
76 pooled CR rate
77 pooled overall response rate
78 potential factors
79 products
80 progression-free survival
81 rate
82 receptors
83 release syndrome
84 response
85 response rate
86 results
87 retroviral vectors
88 review
89 safety
90 search
91 study
92 subgroup analysis
93 survival
94 syndrome
95 systematic review
96 terms
97 therapy
98 toxicity
99 transduction
100 treatment options
101 vector
102 schema:name Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma
103 schema:pagination 164
104 schema:productId N0bcb5627d7bf4759a22d0229f9746fb8
105 Nd20aa4e26a4c41b28a293f3546872ab6
106 Ne9c237a47918436592c7a94f209772e4
107 schema:sameAs https://app.dimensions.ai/details/publication/pub.1132951048
108 https://doi.org/10.1186/s13045-020-01001-1
109 schema:sdDatePublished 2022-12-01T06:40
110 schema:sdLicense https://scigraph.springernature.com/explorer/license/
111 schema:sdPublisher N7b6ed05a34c64c899c133a89a803b177
112 schema:url https://doi.org/10.1186/s13045-020-01001-1
113 sgo:license sg:explorer/license/
114 sgo:sdDataset articles
115 rdf:type schema:ScholarlyArticle
116 N03b0135a17e24515a8681b7abcd96c4b rdf:first sg:person.0716461200.52
117 rdf:rest Nfa784555db1849ad87a540158106d549
118 N0bcb5627d7bf4759a22d0229f9746fb8 schema:name doi
119 schema:value 10.1186/s13045-020-01001-1
120 rdf:type schema:PropertyValue
121 N0f1d1c25daca4c76810148204b624f8f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
122 schema:name Progression-Free Survival
123 rdf:type schema:DefinedTerm
124 N21236d0a7b7a48dab8153555a4ecaf4d rdf:first sg:person.012024353123.35
125 rdf:rest Nfca6f8819b9c443483b63b34e1b10d53
126 N3264e42fa685488eb6205a8e798ab9be schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
127 schema:name Cytokine Release Syndrome
128 rdf:type schema:DefinedTerm
129 N408b9c0f192b4a24a0dcc1a1d0cdacb7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
130 schema:name Treatment Outcome
131 rdf:type schema:DefinedTerm
132 N43701acbe9a24a0cb7c1cfe4e52b3cdf rdf:first sg:person.01341351131.75
133 rdf:rest rdf:nil
134 N4c853d8bc1624608b749b404fec59f35 schema:issueNumber 1
135 rdf:type schema:PublicationIssue
136 N6ac92bbfd0ca475bae71c266fa5a24b5 rdf:first sg:person.016565367053.55
137 rdf:rest Nb125aec403014d8a953e6870e032ab2d
138 N6ee003b9f04d4d4bbd87868a1aee68a4 rdf:first sg:person.010621545656.01
139 rdf:rest N6ac92bbfd0ca475bae71c266fa5a24b5
140 N73f6704f8739442d86ecffe004e2c7cc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
141 schema:name B-Cell Maturation Antigen
142 rdf:type schema:DefinedTerm
143 N78de622a42d745e4b2341491c87bfd44 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
144 schema:name Multiple Myeloma
145 rdf:type schema:DefinedTerm
146 N7b6ed05a34c64c899c133a89a803b177 schema:name Springer Nature - SN SciGraph project
147 rdf:type schema:Organization
148 Nb125aec403014d8a953e6870e032ab2d rdf:first sg:person.01352625767.77
149 rdf:rest Nf6aec6de495c4f9da3ce0fcd6a538bd8
150 Nb6e963680dfc419abd97166461ac6abf schema:volumeNumber 13
151 rdf:type schema:PublicationVolume
152 Nbdc9df91cb76457ba32abf30de89dddf schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
153 schema:name Humans
154 rdf:type schema:DefinedTerm
155 Nbf85ab0e29fc40c3b183e979c1807479 rdf:first sg:person.0660155350.49
156 rdf:rest N43701acbe9a24a0cb7c1cfe4e52b3cdf
157 Nd20aa4e26a4c41b28a293f3546872ab6 schema:name dimensions_id
158 schema:value pub.1132951048
159 rdf:type schema:PropertyValue
160 Ne53c37acf0604bbbb6fc188f1115132c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
161 schema:name Receptors, Chimeric Antigen
162 rdf:type schema:DefinedTerm
163 Ne549f6de877948f399fe78defbe5ebb4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
164 schema:name Immunotherapy, Adoptive
165 rdf:type schema:DefinedTerm
166 Ne9c237a47918436592c7a94f209772e4 schema:name pubmed_id
167 schema:value 33272302
168 rdf:type schema:PropertyValue
169 Nf56c7588d6604d2ab1565c21057e36da schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
170 schema:name Neurotoxicity Syndromes
171 rdf:type schema:DefinedTerm
172 Nf6aec6de495c4f9da3ce0fcd6a538bd8 rdf:first sg:person.010035360171.51
173 rdf:rest N21236d0a7b7a48dab8153555a4ecaf4d
174 Nf8dcf1c0f5064337ae53430ff3ebce74 rdf:first sg:person.01104533052.91
175 rdf:rest Nbf85ab0e29fc40c3b183e979c1807479
176 Nfa784555db1849ad87a540158106d549 rdf:first sg:person.0715102045.57
177 rdf:rest Nf8dcf1c0f5064337ae53430ff3ebce74
178 Nfca6f8819b9c443483b63b34e1b10d53 rdf:first sg:person.0653223122.50
179 rdf:rest N03b0135a17e24515a8681b7abcd96c4b
180 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
181 schema:name Medical and Health Sciences
182 rdf:type schema:DefinedTerm
183 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
184 schema:name Clinical Sciences
185 rdf:type schema:DefinedTerm
186 sg:journal.1039771 schema:issn 1756-8722
187 schema:name Journal of Hematology & Oncology
188 schema:publisher Springer Nature
189 rdf:type schema:Periodical
190 sg:person.010035360171.51 schema:affiliation grid-institutes:grid.5284.b
191 schema:familyName Campillo-Davo
192 schema:givenName Diana
193 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010035360171.51
194 rdf:type schema:Person
195 sg:person.010621545656.01 schema:affiliation grid-institutes:grid.5284.b
196 schema:familyName Roex
197 schema:givenName Gils
198 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010621545656.01
199 rdf:type schema:Person
200 sg:person.01104533052.91 schema:affiliation grid-institutes:grid.5284.b
201 schema:familyName Lion
202 schema:givenName Eva
203 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01104533052.91
204 rdf:type schema:Person
205 sg:person.012024353123.35 schema:affiliation grid-institutes:grid.5284.b
206 schema:familyName Flumens
207 schema:givenName Donovan
208 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012024353123.35
209 rdf:type schema:Person
210 sg:person.01341351131.75 schema:affiliation grid-institutes:grid.411414.5
211 schema:familyName Anguille
212 schema:givenName Sébastien
213 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01341351131.75
214 rdf:type schema:Person
215 sg:person.01352625767.77 schema:affiliation grid-institutes:grid.411414.5
216 schema:familyName Wouters
217 schema:givenName Kristien
218 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01352625767.77
219 rdf:type schema:Person
220 sg:person.016565367053.55 schema:affiliation grid-institutes:grid.411414.5
221 schema:familyName Timmers
222 schema:givenName Marijke
223 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016565367053.55
224 rdf:type schema:Person
225 sg:person.0653223122.50 schema:affiliation grid-institutes:grid.411414.5
226 schema:familyName Schroyens
227 schema:givenName Wilfried
228 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0653223122.50
229 rdf:type schema:Person
230 sg:person.0660155350.49 schema:affiliation grid-institutes:grid.411405.5
231 schema:familyName Luo
232 schema:givenName Feifei
233 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0660155350.49
234 rdf:type schema:Person
235 sg:person.0715102045.57 schema:affiliation grid-institutes:grid.411414.5
236 schema:familyName Berneman
237 schema:givenName Zwi N.
238 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0715102045.57
239 rdf:type schema:Person
240 sg:person.0716461200.52 schema:affiliation grid-institutes:grid.8547.e
241 schema:familyName Chu
242 schema:givenName Yiwei
243 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0716461200.52
244 rdf:type schema:Person
245 sg:pub.10.1038/s41375-019-0669-4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1122956360
246 https://doi.org/10.1038/s41375-019-0669-4
247 rdf:type schema:CreativeWork
248 sg:pub.10.1038/s41375-020-0734-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1124844369
249 https://doi.org/10.1038/s41375-020-0734-z
250 rdf:type schema:CreativeWork
251 sg:pub.10.1038/s41467-019-14119-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1124098340
252 https://doi.org/10.1038/s41467-019-14119-9
253 rdf:type schema:CreativeWork
254 sg:pub.10.1038/s41586-019-1054-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1113006931
255 https://doi.org/10.1038/s41586-019-1054-1
256 rdf:type schema:CreativeWork
257 sg:pub.10.1038/s41591-018-0010-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1103686011
258 https://doi.org/10.1038/s41591-018-0010-1
259 rdf:type schema:CreativeWork
260 sg:pub.10.1186/s13045-018-0653-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1107214929
261 https://doi.org/10.1186/s13045-018-0653-x
262 rdf:type schema:CreativeWork
263 sg:pub.10.1186/s13045-018-0672-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1107776019
264 https://doi.org/10.1186/s13045-018-0672-7
265 rdf:type schema:CreativeWork
266 sg:pub.10.1186/s13045-018-0681-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1110812362
267 https://doi.org/10.1186/s13045-018-0681-6
268 rdf:type schema:CreativeWork
269 sg:pub.10.1186/s13045-019-0823-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1122783824
270 https://doi.org/10.1186/s13045-019-0823-5
271 rdf:type schema:CreativeWork
272 sg:pub.10.1186/s13045-020-00962-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1130921904
273 https://doi.org/10.1186/s13045-020-00962-7
274 rdf:type schema:CreativeWork
275 grid-institutes:grid.411405.5 schema:alternateName Department of Digestive Diseases, Huashan Hospital of Fudan University, Shanghai, China
276 schema:name Biotherapy Research Center, Fudan University, Shanghai, China
277 Department of Digestive Diseases, Huashan Hospital of Fudan University, Shanghai, China
278 rdf:type schema:Organization
279 grid-institutes:grid.411414.5 schema:alternateName Clinical Trial Center, Antwerp University Hospital, Edegem, Belgium
280 Division of Hematology and Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium
281 schema:name Clinical Trial Center, Antwerp University Hospital, Edegem, Belgium
282 Division of Hematology and Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, Edegem, Belgium
283 Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
284 rdf:type schema:Organization
285 grid-institutes:grid.5284.b schema:alternateName Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
286 schema:name Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
287 rdf:type schema:Organization
288 grid-institutes:grid.8547.e schema:alternateName Biotherapy Research Center, Fudan University, Shanghai, China
289 schema:name Biotherapy Research Center, Fudan University, Shanghai, China
290 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...