TY - JOUR
T1 - Tisagenlecleucel immunogenicity in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma
AU - Mueller, Karen Thudium
AU - Grupp, Stephan A.
AU - Maude, Shannon L.
AU - Levine, John E.
AU - Pulsipher, Michael A.
AU - Boyer, Michael W.
AU - August, Keith J.
AU - Doug Myers, G.
AU - Tam, Constantine S.
AU - Jaeger, Ulrich
AU - Foley, Stephen Ronan
AU - Borchmann, Peter
AU - Schuster, Stephen J.
AU - Waller, Edmund K.
AU - Awasthi, Rakesh
AU - Potthoff, Bernd
AU - Warren, Andy
AU - Waldron, Edward R.
AU - McBlane, Fraser
AU - Chassot-Agostinho, Andrea
AU - Laetsch, Theodore W.
N1 - Publisher Copyright:
© 2021 American Society of Hematology. All rights reserved.
PY - 2021/12/14
Y1 - 2021/12/14
N2 - 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 tisagenlecleucel 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 5 143) and the JULIET trial (#NCT02445248) in r/r DLBCL (N 5 115). 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-g 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 tisagenlecleucel cellular kinetics, including maximum concentration and persistence (r2 , 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 tisagenlecleucel in patients with r/r B-ALL or r/r DLBCL.
AB - 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 tisagenlecleucel 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 5 143) and the JULIET trial (#NCT02445248) in r/r DLBCL (N 5 115). 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-g 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 tisagenlecleucel cellular kinetics, including maximum concentration and persistence (r2 , 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 tisagenlecleucel in patients with r/r B-ALL or r/r DLBCL.
UR - https://www.scopus.com/pages/publications/85121745174
U2 - 10.1182/bloodadvances.2020003844
DO - 10.1182/bloodadvances.2020003844
M3 - Article
C2 - 34432863
AN - SCOPUS:85121745174
SN - 2473-9529
VL - 5
SP - 4980
EP - 4991
JO - Blood advances
JF - Blood advances
ER -