Universität zu Köln

Mueller, Karen Thudium, Grupp, Stephan A., Maude, Shannon L., Levine, John E., Pulsipher, Michael A., Boyer, Michael W., August, Keith J., Myers, G. Doug, Tam, Constantine S., Jaeger, Ulrich, Foley, Stephen Ronan, Borchmann, Peter, Schuster, Stephen J., Waller, Edmund K., Awasthi, Rakesh, Potthoff, Bernd, Warren, Andy, Waldron, Edward R., McBlane, Fraser, Chassot-Agostinho, Andrea and Laetsch, Theodore W. (2021). Tisagenlecleucel immunogenicity in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma. Blood Adv., 5 (23). S. 4980 - 4992. AMSTERDAM: ELSEVIER. ISSN 2473-9537

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Abstract

Tisagenlecleucel is indicated for pediatric and young adult patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and adult patients with r/r diffuse large B-cell lymphoma (DLBCL). The tisagenlecleucel chimeric antigen receptor (CAR) contains a murine single-chain variable fragment domain; we examined the effects of humoral and cellular immune responses to tisagenledeucel on clinical outcomes using 2 validated assays. Data were pooled from the ELIANA (registered at www.clinicaltrials.gov as #NCT02435849) and ENSIGN (#NCT02228096) trials in r/r B-ALL (N = 143) and the JULIET trial (#NCT02445248) in r/r DLBCL (N = 115). Humoral responses were determined by flow cytometric measurement of anti-murine CAR19 (mCAR19) antibodies in serum. Cellular responses were determined using T-cell production of interferon-y in response to 2 different pools of mCAR19 peptides. Pretreatment anti-mCAR19 antibodies were detected in 81% of patients with r/r B-ALL and 94% of patients with r/r DLBCL. Posttreatment anti-mCAR19 antibodies were higher than patient-specific baseline in 42% of r/r B-ALL and 9% of r/r DLBCL patients. Pretreatment and posttreatment anti-mCAR19 antibodies did not affect tisagenledeucel cellular kinetics, including maximum concentration and persistence (r(2) < 0.05), clinical response (day-28 response, duration of response, and event-free survival), and safety. T-cell responses were consistent over time, with net responses <1% at baseline and posttreatment time points in a majority of patients and no effect on transgene expansion or persistence or outcomes. Presence of baseline and/or posttreatment anti-mCAR19 antibodies or T-cell responses did not alter the activity of tisagenledeucel in patients with r/r B-ALL or r/r DLBCL.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mueller, Karen Thudium UNSPECIFIED UNSPECIFIED UNSPECIFIED Grupp, Stephan A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Maude, Shannon L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Levine, John E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pulsipher, Michael A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boyer, Michael W. UNSPECIFIED UNSPECIFIED UNSPECIFIED August, Keith J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Myers, G. Doug UNSPECIFIED UNSPECIFIED UNSPECIFIED Tam, Constantine S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaeger, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Foley, Stephen Ronan UNSPECIFIED UNSPECIFIED UNSPECIFIED Borchmann, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuster, Stephen J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Waller, Edmund K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Awasthi, Rakesh UNSPECIFIED UNSPECIFIED UNSPECIFIED Potthoff, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Warren, Andy UNSPECIFIED UNSPECIFIED UNSPECIFIED Waldron, Edward R. UNSPECIFIED UNSPECIFIED UNSPECIFIED McBlane, Fraser UNSPECIFIED UNSPECIFIED UNSPECIFIED Chassot-Agostinho, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Laetsch, Theodore W. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-605077
DOI:	10.1182/bloodadvances.2020003844
Journal or Publication Title:	Blood Adv.
Volume:	5
Number:	23
Page Range:	S. 4980 - 4992
Date:	2021
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	2473-9537
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CLINICAL-PHARMACOLOGY; T-CELLS; ANTIBODIES; AUTOANTIBODIES; PRODUCTS; KINETICS Multiple languages Hematology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60507