Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma


  • M.R. Bishop
  • M. Dickinson
  • D. Purtill
  • P. Barba
  • A. Santoro
  • N. Hamad
  • K. Kato
  • A. Sureda
  • R. Greil
  • C. Thieblemont
  • F. Morschhauser
  • M. Janz
  • I. Flinn
  • W. Rabitsch
  • Y.L. Kwong
  • M.J Kersten
  • M.C. Minnema
  • H. Holte
  • E.H.L. Chan
  • J. Martinez-Lopez
  • A.M.S. Müller
  • R.T. Maziarz
  • J.P. McGuirk
  • E. Bachy
  • S. Le Gouill
  • M. Dreyling
  • H. Harigae
  • D. Bond
  • C. Andreadis
  • P. McSweeney
  • M. Kharfan-Dabaja
  • S. Newsome
  • E. Degtyarev
  • R. Awasthi
  • C. Del Corral
  • G. Andreola
  • A. Masood
  • S.J. Schuster
  • U. Jäger
  • P. Borchmann
  • J.R. Westin


  • New England Journal of Medicine


  • N Engl J Med 386 (7): 629-639


  • 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 number, NCT03570892.).