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Prophylactic Tocilizumab Prior to Anti-CD19 CAR-T Cell Therapy for Non-Hodgkin Lymphoma.
- Source :
-
Frontiers in immunology [Front Immunol] 2021 Oct 12; Vol. 12, pp. 745320. Date of Electronic Publication: 2021 Oct 12 (Print Publication: 2021). - Publication Year :
- 2021
-
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.<br />Competing Interests: BD is a previous employee of Lentigen, a Miltenyi Biotec Company, and has Patents and Royalties related to CAR-T immunotherapy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2021 Caimi, Pacheco Sanchez, Sharma, Otegbeye, Ahmed, Rojas, Patel, Kleinsorge Block, Schiavone, Zamborsky, Boughan, Hillian, Reese-Koc, Maschan, Dropulic, Sekaly and de Lima.)
- Subjects :
- Adrenal Cortex Hormones therapeutic use
Adult
Aged
Antibodies, Monoclonal, Humanized administration & dosage
C-Reactive Protein analysis
Cytokine Release Syndrome blood
Cytokines blood
Drug Administration Schedule
Female
Ferritins blood
Humans
Interleukin 1 Receptor Antagonist Protein therapeutic use
Kaplan-Meier Estimate
Lymphoma, Large B-Cell, Diffuse blood
Lymphoma, Large B-Cell, Diffuse therapy
Lymphoma, Non-Hodgkin blood
Male
Middle Aged
Neurotoxicity Syndromes etiology
Premedication
Progression-Free Survival
Receptors, Interleukin-6 antagonists & inhibitors
Salvage Therapy
Severity of Illness Index
Treatment Outcome
Antibodies, Monoclonal, Humanized therapeutic use
Cytokine Release Syndrome prevention & control
Immunotherapy, Adoptive adverse effects
Lymphoma, Non-Hodgkin therapy
Neurotoxicity Syndromes prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34712233
- Full Text :
- https://doi.org/10.3389/fimmu.2021.745320