2. Academic Validation
  3. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial

Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial

  • Nat Med. 2022 Feb;28(2):325-332. doi: 10.1038/s41591-021-01622-0.
Nathan Hale Fowler 1 2,  Michael Dickinson 3,  Martin Dreyling 4,  Joaquin Martinez-Lopez 5,  Arne Kolstad 6,  Jason Butler 7,  Monalisa Ghosh 8,  Leslie Popplewell 9,  Julio C Chavez 10,  Emmanuel Bachy 11,  Koji Kato 12,  Hideo Harigae 13,  Marie José Kersten 14,  Charalambos Andreadis 15,  Peter A Riedell 16,  P Joy Ho 17,  José Antonio Pérez-Simón 18,  Andy I Chen 19,  Loretta J Nastoupil 20,  Bastian von Tresckow 21 22,  Andrés José María Ferreri 23,  Takanori Teshima 24,  Piers E M Patten 25 26,  Joseph P McGuirk 27,  Andreas L Petzer 28,  Fritz Offner 29,  Andreas Viardot 30,  Pier Luigi Zinzani 31 32,  Ram Malladi 33,  Aiesha Zia 34,  Rakesh Awasthi 35,  Aisha Masood 36,  Oezlem Anak 34,  Stephen J Schuster 37,  Catherine Thieblemont 38
Affiliations

Affiliations

  • 1 The University of Texas MD Anderson Cancer Center, Houston, TX, USA. [email protected].
  • 2 BostonGene, Waltham, MA, USA. [email protected].
  • 3 Peter MacCallum Cancer Centre, Royal Melbourne Hospital and the Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
  • 4 Medizinische Klinik III, LMU Klinikum, Munich, Germany.
  • 5 Hospital 12 De Octubre, Complutense University, CNIO, Madrid, Spain.
  • 6 Oslo University Hospital, Oslo, Norway.
  • 7 Royal Brisbane Hospital, Herston, Queensland, Australia.
  • 8 Michigan Medicine University of Michigan, Ann Arbor, MI, USA.
  • 9 City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
  • 10 Moffitt Cancer Center, Tampa, FL, USA.
  • 11 Hospices Civils de Lyon and Université Claude Bernard Lyon 1, Lyon, France.
  • 12 Kyushu University Hospital, Fukuoka, Japan.
  • 13 Tohoku University Hospital, Sendai, Japan.
  • 14 Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands.
  • 15 Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
  • 16 University of Chicago Medical Center, Chicago, IL, USA.
  • 17 Royal Prince Alfred Hospital and University of Sydney, Camperdown, New South Wales, Australia.
  • 18 Department of Hematology, University Hospital Virgen del Rocío, Instituto de Biomedicina de Sevilla, Universidad de Sevilla, Seville, Spain.
  • 19 Oregon Health and Science University, Portland, OR, USA.
  • 20 The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • 21 Department I of Internal Medicine, Medical Faculty and University Hospital Cologne, University of Cologne, Cologne, Germany.
  • 22 Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • 23 Lymphoma Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
  • 24 Hokkaido University Hospital, Sapporo, Japan.
  • 25 Comprehensive Cancer Centre, King's College London, London, UK.
  • 26 Department of Haematology, King's College Hospital, London, UK.
  • 27 University of Kansas Hospital and Medical Center, Westwood, KS, USA.
  • 28 Internal Medicine I, Ordensklinikum Linz Barmherzige Schwestern-Elisabethinen, Linz, Austria.
  • 29 UZ Gent, Gent, Belgium.
  • 30 Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.
  • 31 IRCCS Azienda Ospedaliero-Universitaria di Bologna Istituto di Ematologia "Seràgnoli", Bologna, Italy.
  • 32 Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy.
  • 33 Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
  • 34 Novartis Pharma AG, Basel, Switzerland.
  • 35 Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.
  • 36 Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
  • 37 Lymphoma Program, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
  • 38 Hôpital Saint-Louis, Paris, France.
PMID: 34921238 DOI: 10.1038/s41591-021-01622-0
Abstract

Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor-T cell therapy with clinically meaningful outcomes demonstrated in patients with relapsed/refractory (r/r) B-cell lymphoma. In a previous pilot study of tisagenlecleucel in r/r follicular lymphoma (FL), 71% of patients achieved a complete response (CR). Here we report the primary, prespecified interim analysis of the ELARA phase 2 multinational trial of tisagenlecleucel in adults with r/r FL after two or more treatment lines or who relapsed after autologous stem cell transplant (no. NCT03568461). The primary endpoint was CR rate (CRR). Secondary endpoints included overall response rate (ORR), duration of response, progression-free survival, overall survival, pharmacokinetics and safety. As of 29 March 2021, 97/98 enrolled patients received tisagenlecleucel (median follow-up, 16.59 months; interquartile range, 13.8-20.21). The primary endpoint was met. In the efficacy set (n = 94), CRR was 69.1% (95% confidence interval, 58.8-78.3) and ORR 86.2% (95% confidence interval, 77.5-92.4). Within 8 weeks of infusion, rates of cytokine release syndrome were 48.5% (grade ≥3, 0%), neurological events 37.1% (grade ≥3, 3%) and immune effector cell-associated neurotoxicity syndrome (ICANS) 4.1% (grade ≥3, 1%) in the safety set (n = 97), with no treatment-related deaths. Tisagenlecleucel is safe and effective in extensively pretreated r/r FL, including in high-risk patients.

Figures
Products