Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma

JULIET Investigators

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Background: Patients with diffuse large B-cell lymphoma that is refractory to primary and secondline therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study. Methods: We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation. The primary end point was the best overall response rate (i.e., the percentage of patients who had a complete or partial response), as judged by an independent review committee. Results: A total of 93 patients received an infusion and were included in the evaluation of efficacy. The median time from infusion to data cutoff was 14 months (range, 0.1 to 26). The best overall response rate was 52% (95% confidence interval, 41 to 62); 40% of the patients had complete responses, and 12% had partial responses. Response rates were consistent across prognostic subgroups. At 12 months after the initial response, the rate of relapse-free survival was estimated to be 65% (79% among patients with a complete response). The most common grade 3 or 4 adverse events of special interest included cytokine release syndrome (22%), neurologic events (12%), cytopenias lasting more than 28 days (32%), infections (20%), and febrile neutropenia (14%). Three patients died from disease progression within 30 days after infusion. No deaths were attributed to tisagenlecleucel, cytokine release syndrome, or cerebral edema. No differences between response groups in tumor expression of CD19 or immune checkpoint- related proteins were found. Conclusions: In this international study of CAR T-cell therapy in relapsed or refractory diffuse large B-cell lymphoma in adults, high rates of durable responses were produced with the use of tisagenlecleucel.

Original languageEnglish (US)
Pages (from-to)45-56
Number of pages12
JournalNew England Journal of Medicine
Volume380
Issue number1
DOIs
StatePublished - Jan 3 2019

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Lymphoma, Large B-Cell, Diffuse
Antigen Receptors
Cell- and Tissue-Based Therapy
Disease Progression
Cytokines
Febrile Neutropenia
Hematopoietic Stem Cell Transplantation
Brain Edema
Anniversaries and Special Events
Stem Cell Transplantation
B-Cell Lymphoma
Advisory Committees
Nervous System
B-Lymphocytes
Confidence Intervals
Recurrence
Survival
Infection
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. / JULIET Investigators.

In: New England Journal of Medicine, Vol. 380, No. 1, 03.01.2019, p. 45-56.

Research output: Contribution to journalArticle

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title = "Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma",
abstract = "Background: Patients with diffuse large B-cell lymphoma that is refractory to primary and secondline therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study. Methods: We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation. The primary end point was the best overall response rate (i.e., the percentage of patients who had a complete or partial response), as judged by an independent review committee. Results: A total of 93 patients received an infusion and were included in the evaluation of efficacy. The median time from infusion to data cutoff was 14 months (range, 0.1 to 26). The best overall response rate was 52{\%} (95{\%} confidence interval, 41 to 62); 40{\%} of the patients had complete responses, and 12{\%} had partial responses. Response rates were consistent across prognostic subgroups. At 12 months after the initial response, the rate of relapse-free survival was estimated to be 65{\%} (79{\%} among patients with a complete response). The most common grade 3 or 4 adverse events of special interest included cytokine release syndrome (22{\%}), neurologic events (12{\%}), cytopenias lasting more than 28 days (32{\%}), infections (20{\%}), and febrile neutropenia (14{\%}). Three patients died from disease progression within 30 days after infusion. No deaths were attributed to tisagenlecleucel, cytokine release syndrome, or cerebral edema. No differences between response groups in tumor expression of CD19 or immune checkpoint- related proteins were found. Conclusions: In this international study of CAR T-cell therapy in relapsed or refractory diffuse large B-cell lymphoma in adults, high rates of durable responses were produced with the use of tisagenlecleucel.",
author = "{JULIET Investigators} and Schuster, {Stephen J.} and Bishop, {Michael R.} and Tam, {Constantine S.} and Waller, {Edmund K.} and Peter Borchmann and McGuirk, {Joseph P.} and Ulrich J{\"a}ger and Samantha Jaglowski and Charalambos Andreadis and Westin, {Jason R.} and Isabelle Fleury and Veronika Bachanova and Foley, {S. Ronan} and Ho, {P. Joy} and Stephan Mielke and Magenau, {John M.} and Harald Holte and Serafino Pantano and Pacaud, {Lida B.} and Rakesh Awasthi and Jufen Chu and {\"O}zlem Anak and Gilles Salles and Richard Maziarz",
year = "2019",
month = "1",
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doi = "10.1056/NEJMoa1804980",
language = "English (US)",
volume = "380",
pages = "45--56",
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T1 - Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma

AU - JULIET Investigators

AU - Schuster, Stephen J.

AU - Bishop, Michael R.

AU - Tam, Constantine S.

AU - Waller, Edmund K.

AU - Borchmann, Peter

AU - McGuirk, Joseph P.

AU - Jäger, Ulrich

AU - Jaglowski, Samantha

AU - Andreadis, Charalambos

AU - Westin, Jason R.

AU - Fleury, Isabelle

AU - Bachanova, Veronika

AU - Foley, S. Ronan

AU - Ho, P. Joy

AU - Mielke, Stephan

AU - Magenau, John M.

AU - Holte, Harald

AU - Pantano, Serafino

AU - Pacaud, Lida B.

AU - Awasthi, Rakesh

AU - Chu, Jufen

AU - Anak, Özlem

AU - Salles, Gilles

AU - Maziarz, Richard

PY - 2019/1/3

Y1 - 2019/1/3

N2 - Background: Patients with diffuse large B-cell lymphoma that is refractory to primary and secondline therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study. Methods: We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation. The primary end point was the best overall response rate (i.e., the percentage of patients who had a complete or partial response), as judged by an independent review committee. Results: A total of 93 patients received an infusion and were included in the evaluation of efficacy. The median time from infusion to data cutoff was 14 months (range, 0.1 to 26). The best overall response rate was 52% (95% confidence interval, 41 to 62); 40% of the patients had complete responses, and 12% had partial responses. Response rates were consistent across prognostic subgroups. At 12 months after the initial response, the rate of relapse-free survival was estimated to be 65% (79% among patients with a complete response). The most common grade 3 or 4 adverse events of special interest included cytokine release syndrome (22%), neurologic events (12%), cytopenias lasting more than 28 days (32%), infections (20%), and febrile neutropenia (14%). Three patients died from disease progression within 30 days after infusion. No deaths were attributed to tisagenlecleucel, cytokine release syndrome, or cerebral edema. No differences between response groups in tumor expression of CD19 or immune checkpoint- related proteins were found. Conclusions: In this international study of CAR T-cell therapy in relapsed or refractory diffuse large B-cell lymphoma in adults, high rates of durable responses were produced with the use of tisagenlecleucel.

AB - Background: Patients with diffuse large B-cell lymphoma that is refractory to primary and secondline therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study. Methods: We conducted an international, phase 2, pivotal study of centrally manufactured tisagenlecleucel involving adult patients with relapsed or refractory diffuse large B-cell lymphoma who were ineligible for or had disease progression after autologous hematopoietic stem-cell transplantation. The primary end point was the best overall response rate (i.e., the percentage of patients who had a complete or partial response), as judged by an independent review committee. Results: A total of 93 patients received an infusion and were included in the evaluation of efficacy. The median time from infusion to data cutoff was 14 months (range, 0.1 to 26). The best overall response rate was 52% (95% confidence interval, 41 to 62); 40% of the patients had complete responses, and 12% had partial responses. Response rates were consistent across prognostic subgroups. At 12 months after the initial response, the rate of relapse-free survival was estimated to be 65% (79% among patients with a complete response). The most common grade 3 or 4 adverse events of special interest included cytokine release syndrome (22%), neurologic events (12%), cytopenias lasting more than 28 days (32%), infections (20%), and febrile neutropenia (14%). Three patients died from disease progression within 30 days after infusion. No deaths were attributed to tisagenlecleucel, cytokine release syndrome, or cerebral edema. No differences between response groups in tumor expression of CD19 or immune checkpoint- related proteins were found. Conclusions: In this international study of CAR T-cell therapy in relapsed or refractory diffuse large B-cell lymphoma in adults, high rates of durable responses were produced with the use of tisagenlecleucel.

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U2 - 10.1056/NEJMoa1804980

DO - 10.1056/NEJMoa1804980

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JF - New England Journal of Medicine

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