2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references47

          • Record: found
          • Abstract: found
          • Article: not found

          Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

          In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia

            In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma

              Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                12 October 2021
                2021
                : 12
                : 745320
                Affiliations
                [1] 1 Department of Hematology and Oncology, Cleveland Clinic, University Hospitals Seidman Cancer Center, and Case Western Reserve University , Cleveland, OH, United States
                [2] 2 Department of Pathology, Emory University , Atlanta, GA, United States
                [3] 3 Department of Medicine, The University of Kansas , Kansas City, KY, United States
                [4] 4 Escuela de Medicina, Pontificia Universidad Católica de Chile , Santiago, Chile
                [5] 5 Dmitryi Rogachev National Medical Research Centre of Pediatric Hematology, Oncology and Immunology , Moscow, Russia
                [6] 6 Lentigen, A Miltenyi Biotec Company , Gaithersburg, MD, United States
                Author notes

                Edited by: Ye Li, University of Texas MD Anderson Cancer Center, United States

                Reviewed by: Saad Kenderian, Mayo Clinic, United States; Xuyao Zhang, Fudan University, China

                *Correspondence: Paolo F. Caimi, caimip@ 123456ccf.org

                †Present address: Paolo F. Caimi, Department of Hematology and Oncology, Cleveland Clinic, Cleveland, OH, United States; Seema Patel, Department of Pharmacy, Cleveland Clinic, Cleveland, OH, United States; Boro Dropulic, Caring Cross, Gaithersburg, MD, United States; Marcos de Lima, Division of Hematology, Department of Medicine, The Ohio State University, Columbus, OH, United States

                This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2021.745320
                8546323
                34712233
                3ed04531-98ba-4180-b97a-2b599b70319b
                Copyright © 2021 Caimi, Pacheco Sanchez, Sharma, Otegbeye, Ahmed, Rojas, Patel, Kleinsorge Block, Schiavone, Zamborsky, Boughan, Hillian, Reese-Koc, Maschan, Dropulic, Sekaly and de Lima

                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.

                History
                : 21 July 2021
                : 21 September 2021
                Page count
                Figures: 3, Tables: 3, Equations: 0, References: 47, Pages: 11, Words: 5668
                Categories
                Immunology
                Original Research

                Immunology
                tocilizumab,car- t cells,lymphoma,prophylaxis,cytokine release syndrome (crs)
                Immunology
                tocilizumab, car- t cells, lymphoma, prophylaxis, cytokine release syndrome (crs)

                Comments

                Comment on this article