Universität zu Köln

Schuster, Stephen J., Bishop, Michael R., Tam, Constantine S., Waller, Edmund K., Borchmann, Peter, McGuirk, Joseph P., Jaeger, Ulrich, Jaglowski, Samantha, Andreadis, Charalambos, Westin, Jason R., Fleury, Isabelle, Bachanova, Veronika, Foley, S. Ronan, Ho, P. Joy p, Mielke, Stephan ORCID: 0000-0002-8325-9215, Magenau, John M., Holte, Harald, Pantano, Serafino, Pacaud, Lida B., Awasthi, Rakesh, Chu, Jufen, Anak, Ozlem, Salles, Gilles and Maziarz, Richard T. (2019). Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N. Engl. J. Med., 380 (1). S. 45 - 57. WALTHAM: MASSACHUSETTS MEDICAL SOC. ISSN 1533-4406

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Abstract

BACKGROUND Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stern-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 0 10 (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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schuster, Stephen J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bishop, Michael R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tam, Constantine S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Waller, Edmund K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Borchmann, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED McGuirk, Joseph P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaeger, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaglowski, Samantha UNSPECIFIED UNSPECIFIED UNSPECIFIED Andreadis, Charalambos UNSPECIFIED UNSPECIFIED UNSPECIFIED Westin, Jason R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fleury, Isabelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Bachanova, Veronika UNSPECIFIED UNSPECIFIED UNSPECIFIED Foley, S. Ronan UNSPECIFIED UNSPECIFIED UNSPECIFIED Ho, P. Joy p UNSPECIFIED UNSPECIFIED UNSPECIFIED Mielke, Stephan UNSPECIFIED orcid.org/0000-0002-8325-9215 UNSPECIFIED Magenau, John M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Holte, Harald UNSPECIFIED UNSPECIFIED UNSPECIFIED Pantano, Serafino UNSPECIFIED UNSPECIFIED UNSPECIFIED Pacaud, Lida B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Awasthi, Rakesh UNSPECIFIED UNSPECIFIED UNSPECIFIED Chu, Jufen UNSPECIFIED UNSPECIFIED UNSPECIFIED Anak, Ozlem UNSPECIFIED UNSPECIFIED UNSPECIFIED Salles, Gilles UNSPECIFIED UNSPECIFIED UNSPECIFIED Maziarz, Richard T. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-159538
DOI:	10.1056/NEJMoa1804980
Journal or Publication Title:	N. Engl. J. Med.
Volume:	380
Number:	1
Page Range:	S. 45 - 57
Date:	2019
Publisher:	MASSACHUSETTS MEDICAL SOC
Place of Publication:	WALTHAM
ISSN:	1533-4406
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SALVAGE REGIMENS; TRANSPLANTATION; CHEMOTHERAPY; OUTCOMES Multiple languages Medicine, General & Internal Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15953