Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma

Bishop, MR; Dickinson, M; Purtill, D; Barba, P; Santoro, A; Hamad, N; Kato, K; Sureda, A; Greil, R; Thieblemont, C; Morschhauser, F; Janz, M; Flinn, I; Rabitsch, W; Kwong, YL; Kersten, MJ; Minnema, MC; Holte, H; Chan, EHL; Martinez-Lopez, J; Muller, AMS; Maziarz, RT; McGuirk, JP; Bachy, E; Le Gouill, S; Dreyling, M; Harigae, H; Bond, D; Andreadis, C; McSweeney, P; Kharfan-Dabaja, M; Newsome, S; Degtyarev, E; Awasthi, R; Del Corral, C; Andreola, G; Masood, A; Schuster, SJ; Jager, U; Borchmann, P; Westin, JR

Author(s): Bishop, MR; Dickinson, M; Purtill, D; Barba, P; Santoro, A; Hamad, N; Kato, K; Sureda, A; Greil, R; Thieblemont, C; Morschhauser, F; Janz, M; Flinn, I; Rabitsch, W; Kwong, YL; Kersten, MJ; Minnema, MC; Holte, H; Chan, EHL; Martinez-Lopez, J; Muller, AMS; Maziarz, RT; McGuirk, JP; Bachy, E; Le Gouill, S; Dreyling, M; Harigae, H; Bond, D; Andreadis, C; McSweeney, P; Kharfan-Dabaja, M; Newsome, S; Degtyarev, E; Awasthi, R; Del Corral, C; Andreola, G; Masood, A; Schuster, SJ; Jager, U; Borchmann, P; Westin, JR;
Details: Publication Year 2022-02-17,Volume 386,Issue #7,Page 629-639
Journal Title: New England Journal of Medicine
Publication Type: Research 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 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.).
Keywords: Adult; Aged; Antineoplastic Agents, Immunological/adverse effects/*therapeutic use; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use; Combined Modality Therapy; Female; *Hematopoietic Stem Cell Transplantation; Humans; *Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse/*drug therapy/mortality/therapy; Male; Middle Aged; Progression-Free Survival; Receptors, Antigen, T-Cell/*therapeutic use; Receptors, Chimeric Antigen/*antagonists & inhibitors; Salvage Therapy; Transplantation, Autologous
Department(s): Clinical Haematology
PubMed ID: 34904798
Publisher's Version: https://doi.org/10.1056/NEJMoa2116596
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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