Schuster, Stephen J., Tam, Constantine S., Borchmann, Peter, Worel, Nina, McGuirk, Joseph P., Holte, Harald, Waller, Edmund K., Jaglowski, Samantha, Bishop, Michael R., Damon, Lloyd E., Foley, Stephen Ronan, Westin, Jason R., Fleury, Isabelle, Ho, P. Joy, Mielke, Stephan ORCID: 0000-0002-8325-9215, Teshima, Takanori, Janakiram, Murali, Hsu, Jing-Mei, Izutsu, Koji, Kersten, Marie Jose, Ghosh, Monalisa, Wagner-Johnston, Nina, Kato, Koji, Corradini, Paolo, Martinez-Prieto, Marcela, Han, Xia, Tiwari, Ranjan, Salles, Gilles and Maziarz, Richard T. (2021). Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol., 22 (10). S. 1403 - 1416. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1474-5488

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Abstract

Background In the primary analysis of the pivotal JULIET trial of tisagenlecleucel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, the best overall response rate was 52% and the complete response rate was 40% in 93 evaluable adult patients with relapsed or refractory aggressive B-cell lymphomas. We aimed to do a long-term follow-up analysis of the clinical outcomes and correlative analyses of activity and safety in the full adult cohort. Methods In this multicentre, open-label, single-arm, phase 2 trial (JULIET) done at 27 treatment sites in ten countries (Australia, Austria, Canada, France, Germany, Italy, Japan, the Netherlands, Norway, and the USA), adult patients (>= 18 years) with histologically confirmed relapsed or refractory large B-cell lymphomas who were ineligible for, did not consent to, or had disease progression after autologous haematopoietic stem-cell transplantation, with an Eastern Cooperative Oncology Group performance status of 0-1 at screening, were enrolled. Patients received a single intravenous infusion of tisagenlecleucel (target dose 5 x 108 viable transduced CAR T cells). The primary endpoint was overall response rate (ie, the proportion of patients with a best overall disease response of a complete response or partial response using the Lugano classification, as assessed by an independent review committee) at any time postinfusion and was analysed in all patients who received tisagenlecleucel (the full analysis set). Safety was analysed in all patients who received tisagenlecleucel. JULIET is registered with ClinialTrials.gov, NCT02445248, and is ongoing. Findings Between July 29, 2015, and Nov 2, 2017, 167 patients were enrolled. As of Feb 20, 2020, 115 patients had received tisagenlecleucel infusion and were included in the full analysis set. At a median follow-up of 40.3 months (IQR 37.8-43.8), the overall response rate was 53.0% (95% CI 43.5-62.4; 61 of 115 patients), with 45 (39%) patients having a complete response as their best overall response. The most common grade 3-4 adverse events were anaemia (45 [39%]), decreased neutrophil count (39 [34%]), decreased white blood cell count (37 [32%]), decreased platelet count (32 [28%]), cytokine release syndrome (26 [23%]), neutropenia (23 [20%]), febrile neutropenia (19 [17%]), hypophosphataemia (15 [13%]), and thrombocytopenia (14 [12%]). The most common treatment-related serious adverse events were cytokine release syndrome (31 [27%]), febrile neutropenia (seven [6%]), pyrexia (six [5%]), pancytopenia (three [3%]), and pneumonia (three [3%]). No treatment-related deaths were reported. Interpretation Tisagenlecleucel shows durable activity and manageable safety profiles in adult patients with relapsed or refractory aggressive B-cell lymphomas. For patients with large B-cell lymphomas that are refractory to chemoimmunotherapy or relapsing after second-line therapies, tisagenlecleucel compares favourably with respect to risk-benefit relative to conventional therapeutic approaches (eg, salvage chemotherapy). Copyright (C) 2021 Published by Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schuster, Stephen J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tam, Constantine S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borchmann, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Worel, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGuirk, Joseph P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holte, HaraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waller, Edmund K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jaglowski, SamanthaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bishop, Michael R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Damon, Lloyd E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Foley, Stephen RonanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Westin, Jason R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fleury, IsabelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ho, P. JoyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mielke, StephanUNSPECIFIEDorcid.org/0000-0002-8325-9215UNSPECIFIED
Teshima, TakanoriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janakiram, MuraliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hsu, Jing-MeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Izutsu, KojiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kersten, Marie JoseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ghosh, MonalisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner-Johnston, NinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kato, KojiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Corradini, PaoloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martinez-Prieto, MarcelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Han, XiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tiwari, RanjanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salles, GillesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maziarz, Richard T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-607568
DOI: 10.1016/S1470-2045(21)00375-2
Journal or Publication Title: Lancet Oncol.
Volume: 22
Number: 10
Page Range: S. 1403 - 1416
Date: 2021
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1474-5488
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PROGNOSTIC-FACTORS; MANAGEMENT; THERAPY; SURVIVAL; DISEASEMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60756

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