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Chimeric antigen receptor (CAR) T-cell therapy as a treatment option for patients with B-cell lymphomas: perspectives on the therapeutic potential of Axicabtagene ciloleucel

Authors Viardot A, Wais V, Sala E, Koerper S

Received 18 December 2018

Accepted for publication 28 February 2019

Published 25 March 2019 Volume 2019:11 Pages 2393—2404


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Beicheng Sun

Andreas Viardot,1 Verena Wais,1 Elisa Sala,1 Sixten Koerper2,3

1Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany; 2Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, Ulm, Germany; 3Institute of Transfusion Medicine, University of Ulm, Ulm, Germany

Abstract: Axicabtagene lisoleucel (Axi-cel) is the second approved gene-alterating cancer treatment and the first in aggressive lymphoma using the “chimeric antigen receptor” (CAR) technology. T-cells from patients were transfected with CARs and reinfused after a lymphodepleting chemotherapy. CAR T-cells are “living drugs” with the ability to persist and expand after a single infusion. Axi-cel is a “second generation” CAR product characterized by the use of a retroviral gene vector transfer and by CD28 as costimulatory domain. In a phase II trial with heavily pretreated patients with aggressive B-cell lymphoma, the overall response rate was 82% with an ongoing complete response rate of 40% after 6 months – with expectations of long-term remissions and cure, even though follow-up data are still limited. There are some prominent side effects like cytokine release syndrome (Grade 3–5: 13%) and neurotoxicity (Grade 3–5: 28%). Novel strategies for prediction, prevention and treatment of these critical side effects are warranted. There are new concepts to enhance the efficacy and prevent resistance in lymphomas. CAR T-cells represent an extremely evolving field with an inestimable potential in general and particularly in aggressive lymphoma. However, we are still learning how to use Axi-cel and other CAR-T cells compounds effectively to optimize the long-term results.

Keywords: chimeric antigen receptor, CAR T-cells, Axicabtagene ciloleucel, diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, transformed follicular lymphoma, cytokine release syndrome, neurotoxicity, CAR related encephalopathy syndrome

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