Tisagenlecleucel immunogenicity in relapsed/refractory acute lymphoblastic leukemia and diffuse large B-cell lymphoma

Karen Thudium Mueller, Stephan A. Grupp, Shannon L. Maude, John E. Levine, Michael A. Pulsipher, Michael W. Boyer, Keith J. August, G. Doug Myers, Constantine S. Tam, Ulrich Jaeger, Stephen Ronan Foley, Peter Borchmann, Stephen J. Schuster, Edmund K. Waller, Rakesh Awasthi, Bernd Potthoff, Andy Warren, Edward R. Waldron, Fraser McBlane, Andrea Chassot-AgostinhoTheodore W. Laetsch

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


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.

Original languageEnglish
Pages (from-to)4980-4991
Number of pages12
JournalBlood advances
StatePublished - 14 Dec 2021


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