Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma.
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| Abstract | BACKGROUND: Patient outcomes are poor for aggressive B-cell non-Hodgkin's lymphomas not responding to or progressing within 12 months after first-line therapy. Tisagenlecleucel is an anti-CD19 chimeric antigen receptor T-cell therapy approved for diffuse large B-cell lymphoma after at least two treatment lines. METHODS: We conducted an international phase 3 trial involving patients with aggressive lymphoma that was refractory to or progressing within 12 months after first-line therapy. Patients were randomly assigned to receive tisagenlecleucel with optional bridging therapy (tisagenlecleucel group) or salvage chemotherapy and autologous hematopoietic stem-cell transplantation (HSCT) (standard-care group). The primary end point was event-free survival, defined as the time from randomization to stable or progressive disease at or after the week 12 assessment or death. Crossover to receive tisagenlecleucel was allowed if a defined event occurred at or after the week 12 assessment. Other end points included response and safety. RESULTS: A total of 322 patients underwent randomization. At baseline, the percentage of patients with high-grade lymphomas was higher in the tisagenlecleucel group than in the standard-care group (24.1% vs. 16.9%), as was the percentage with an International Prognostic Index score (range, 0 to 5, with higher scores indicating a worse prognosis) of 2 or higher (65.4% vs. 57.5%). A total of 95.7% of the patients in the tisagenlecleucel group received tisagenlecleucel; 32.5% of the patients in the standard-care group received autologous HSCT. The median time from leukapheresis to tisagenlecleucel infusion was 52 days. A total of 25.9% of the patients in the tisagenlecleucel group had lymphoma progression at week 6, as compared with 13.8% of those in the standard-care group. The median event-free survival in both groups was 3.0 months (hazard ratio for event or death in the tisagenlecleucel group, 1.07; 95% confidence interval, 0.82 to 1.40; P = 0.61). A response occurred in 46.3% of the patients in the tisagenlecleucel group and in 42.5% in the standard-care group. Ten patients in the tisagenlecleucel group and 13 in the standard-care group died from adverse events. CONCLUSIONS:
Tisagenlecleucel was not superior to standard salvage therapy in this trial. Additional studies are needed to assess which patients may obtain the most benefit from each approach. (Funded by Novartis; BELINDA ClinicalTrials.gov number, NCT03570892.).
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| Authors | Michael R Bishop, Michael Dickinson, Duncan Purtill, Pere Barba, Armando Santoro, Nada Hamad, Koji Kato, Anna Sureda, Richard Greil, Catherine Thieblemont, Franck Morschhauser, Martin Janz, Ian Flinn, Werner Rabitsch, Yok-Lam Kwong, Marie J Kersten, Monique C Minnema, Harald Holte, Esther H L Chan, Joaquin Martinez-Lopez, Antonia M S Müller, Richard T Maziarz, Joseph P McGuirk, Emmanuel Bachy, Steven Le Gouill, Martin Dreyling, Hideo Harigae, David Bond, Charalambos Andreadis, Peter McSweeney, Mohamed Kharfan-Dabaja, Simon Newsome, Evgeny Degtyarev, Rakesh Awasthi, Christopher Del Corral, Giovanna Andreola, Aisha Masood, Stephen J Schuster, Ulrich Jäger, Peter Borchmann, Jason R Westin |
| Journal | The New England journal of medicine (N Engl J Med) Vol. 386 Issue 7 Pg. 629-639 (02 17 2022) ISSN: 1533-4406 [Electronic] United States |
| PMID | 34904798 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2021 Massachusetts Medical Society. |
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