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Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma

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 in...

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Autores principales: Caimi, Paolo F., Pacheco Sanchez, Gabriela, Sharma, Ashish, Otegbeye, Folashade, Ahmed, Nausheen, Rojas, Patricio, Patel, Seema, Kleinsorge Block, Sarah, Schiavone, Jennifer, Zamborsky, Kayla, Boughan, Kirsten, Hillian, Antoinette, Reese-Koc, Jane, Maschan, Mikhail, Dropulic, Boro, Sekaly, Rafick-Pierre, de Lima, Marcos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546323/
https://www.ncbi.nlm.nih.gov/pubmed/34712233
http://dx.doi.org/10.3389/fimmu.2021.745320
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author Caimi, Paolo F.
Pacheco Sanchez, Gabriela
Sharma, Ashish
Otegbeye, Folashade
Ahmed, Nausheen
Rojas, Patricio
Patel, Seema
Kleinsorge Block, Sarah
Schiavone, Jennifer
Zamborsky, Kayla
Boughan, Kirsten
Hillian, Antoinette
Reese-Koc, Jane
Maschan, Mikhail
Dropulic, Boro
Sekaly, Rafick-Pierre
de Lima, Marcos
author_facet Caimi, Paolo F.
Pacheco Sanchez, Gabriela
Sharma, Ashish
Otegbeye, Folashade
Ahmed, Nausheen
Rojas, Patricio
Patel, Seema
Kleinsorge Block, Sarah
Schiavone, Jennifer
Zamborsky, Kayla
Boughan, Kirsten
Hillian, Antoinette
Reese-Koc, Jane
Maschan, Mikhail
Dropulic, Boro
Sekaly, Rafick-Pierre
de Lima, Marcos
author_sort Caimi, Paolo F.
collection PubMed
description 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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spelling pubmed-85463232021-10-27 Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma Caimi, Paolo F. Pacheco Sanchez, Gabriela Sharma, Ashish Otegbeye, Folashade Ahmed, Nausheen Rojas, Patricio Patel, Seema Kleinsorge Block, Sarah Schiavone, Jennifer Zamborsky, Kayla Boughan, Kirsten Hillian, Antoinette Reese-Koc, Jane Maschan, Mikhail Dropulic, Boro Sekaly, Rafick-Pierre de Lima, Marcos Front Immunol Immunology 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. Frontiers Media S.A. 2021-10-12 /pmc/articles/PMC8546323/ /pubmed/34712233 http://dx.doi.org/10.3389/fimmu.2021.745320 Text en Copyright © 2021 Caimi, Pacheco Sanchez, Sharma, Otegbeye, Ahmed, Rojas, Patel, Kleinsorge Block, Schiavone, Zamborsky, Boughan, Hillian, Reese-Koc, Maschan, Dropulic, Sekaly and de Lima https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Caimi, Paolo F.
Pacheco Sanchez, Gabriela
Sharma, Ashish
Otegbeye, Folashade
Ahmed, Nausheen
Rojas, Patricio
Patel, Seema
Kleinsorge Block, Sarah
Schiavone, Jennifer
Zamborsky, Kayla
Boughan, Kirsten
Hillian, Antoinette
Reese-Koc, Jane
Maschan, Mikhail
Dropulic, Boro
Sekaly, Rafick-Pierre
de Lima, Marcos
Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma
title Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma
title_full Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma
title_fullStr Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma
title_full_unstemmed Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma
title_short Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma
title_sort prophylactic tocilizumab prior to anti-cd19 car-t cell therapy for non-hodgkin lymphoma
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546323/
https://www.ncbi.nlm.nih.gov/pubmed/34712233
http://dx.doi.org/10.3389/fimmu.2021.745320
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