Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma
Bishop, Michael R; Dickinson, Michael; Purtill, Duncan; Barba, Pere; Santoro, Armando; Hamad, Nada; Kato, Koji; Sureda, Anna; Greil, Richard; Thieblemont, Catherine; Morschhauser, Franck; Janz, Martin; Flinn, Ian; Rabitsch, Werner; Kwong, Yok-Lam; Kersten, Marie J; Minnema, Monique C; Holte, Harald; Chan, Esther H L; Martinez-Lopez, Joaquin; Müller, Antonia M S; Maziarz, Richard T; McGuirk, Joseph P; Bachy, Emmanuel; Le Gouill, Steven; Dreyling, Martin; Harigae, Hideo; Bond, David; Andreadis, Charalambos; McSweeney, Peter; Kharfan-Dabaja, Mohamed; Newsome, Simon; Degtyarev, Evgeny; Awasthi, Rakesh; Del Corral, Christopher; Andreola, Giovanna; Masood, Aisha; Schuster, Stephen J; Jäger, Ulrich; Borchmann, Peter; Westin, Jason R
(2022) The New England journal of medicine, volume 386, issue 7, pp. 629 - 639
(Article)
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
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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 standardcare 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.
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Keywords: General Medicine, Journal Article
ISSN: 0028-4793
Publisher: Massachussetts Medical Society
Note: Funding Information: Funded by Novartis; BELINDA ClinicalTrials.gov number, NCT03570892. Publisher Copyright: © 2021 Massachusetts Medical Society.
(Peer reviewed)