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Cited by 121CAR-T cell therapy researchImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

Prophylactic tocilizumab prior to anti-CD19 CAR-T cell therapy for non-Hodgkin lymphoma

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Caimi, Paolo F., Pacheco Sanchez, Gabriela, Sharma, Ashish, Otegbeye, Folashade, Ahmed, Nausheen, Rojas, Patricio, Patel, Seema, Kleinsorge Block, Sarah +9 more·2021·Frontiers in Immunology
DOI 10.3389/fimmu.2021.745320PMC PMC8546323
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Abstract

Anti-CD19 chimeric antigen receptor T (CAR-T) cells have demonstrated activity against relapsed/refractory lymphomas. Cytokine release syndrome (CRS) and immune effector cell - associated neurotoxicity syndrome (ICANS) are well-known complications. Tocilizumab, a monoclonal antibody targeting the interleukin-6 (IL-6) receptor was administered 1 hour prior to infusion of anti-CD19 CAR-T cells with CD3ζ/4-1BB costimulatory signaling used to treat non-Hodgkin lymphoma patients. Relapsed/refractory lymphoma patients treated with anti-CD19 CAR-T cells were included in this analysis. Cytokine plasma levels were measured by electrochemiluminescence before lymphodepleting chemotherapy, prior to infusion and then on days 2, 4,6, and 14 days after treatment. Twenty patients were treated. Cell products included locally manufactured anti-CD19 CAR-T (n=18) and tisagenlecleucel (n=2). There were no adverse events attributed to tocilizumab. Ten patients had grade 1-2 CRS at a median of 4 (range 3-7) days. There were no cases of grade ≥3 CRS. Five patients had ICANS, grade 1 (n=4) and grade 4 (n=1). Laboratory studies obtained prior to lymphodepleting chemotherapy were comparable between patients with and without CRS, except for interleukin (IL)-15 plasma concentrations. patients with CRS had higher post-infusion ferritin and C reactive protein, with more marked increases in inflammatory cytokines, including IL-6, IL-15, IFN-γ, fractalkine and MCP-1. Fifteen patients (75%) achieved CR and 2 (10%), PR. One-year OS and PFS estimates were 83% and 73%. Prophylactic tocilizumab was associated with low CRS incidence and severity. There were no adverse events associated with tocilizumab, no increase in frequency or severity of ICANS and excellent disease control and overall survival.

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  • The LVV was manufactured and tested under a quality management system in compliance with GMP guidelines.

    “The LVV was manufactured and tested under a quality management system in compliance with GMP guidelines and was previously used in numerous clinical studies.26,27,28”

    From Point-of-care manufacturing of anti-CD19 CAR-T cells using a closed production platform: Experiences of an academic in Thailand (2024) · cites this paper as [28]

    The Methods section identifies a lentiviral vector used to manufacture CAR-T cells, but does not describe how the vector itself was manufactured or tested. Searches for GMP compliance and a quality management system found no passage addressing those claims; page numbers are unavailable in our copy. (LLM, conf=0.74)

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Authors
Caimi, P. F., Pacheco Sanchez, G., Sharma, A., Otegbeye, F., Ahmed, N., Rojas, P., Patel, S., Kleinsorge Block, S., Schiavone, J., Zamborsky, K., Boughan, K., Hillian, A., Reese-Koc, J., Maschan, M., Dropulic, B., Sekaly, R.-P., & de Lima, M.
Affiliations
  • Cleveland Clinic (US)
  • Emory University (US)
  • University of Kansas (US)
  • Pontificia Universidad Católica de Chile (CL)
Corresponding author
Caimi, Paolo F.
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2021-10-12
Volume
12
Pages
745320-745320
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2021.745320
PMC
PMC8546323
OpenAlex
W3206099201
Cited by
121
References
48
Citations by year
2026: 13 · 2025: 29 · 2024: 35 · 2023: 23 · 2022: 17 · 2021: 2 · 2013: 1
FWCI
7.38
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
tocilizumab, CD19 CAR T cells, non-Hodgkin lymphoma, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, IL-6 receptor inhibition, tisagenlecleucel, IL-15, inflammatory cytokines, relapsed/refractory lymphoma
MeSH terms
Progression-Free Survival, Cytokine Release Syndrome, Adrenal Cortex Hormones, Adult, Aged, C-Reactive Protein, Drug Administration Schedule, Female, Ferritins, Humans, Lymphoma, Non-Hodgkin, Male, Middle Aged, Premedication, Severity of Illness Index, Cytokines, Immunotherapy, Adoptive, Lymphoma, Large B-Cell, Diffuse, Salvage Therapy, Treatment Outcome, Receptors, Interleukin-6, Neurotoxicity Syndromes, Kaplan-Meier Estimate, Interleukin 1 Receptor Antagonist Protein, Antibodies, Monoclonal, Humanized

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