Pooled safety analysis of tisagenlecleucel in children and young adults with B cell acute lymphoblastic leukemia

John E. Levine, Stephan A. Grupp, Michael A. Pulsipher, Andrew C. DIetz, Susana Rives, G. Douglas Myers, Keith J. August, Michael R. Verneris, Jochen Buechner, Theodore W. Laetsch, Henrique Bittencourt, Andre Baruchel, Michael W. Boyer, Barbara De Moerloose, Muna Qayed, Stella M. Davies, Christine L. Phillips, Timothy A. Driscoll, Peter Bader, Krysta SchlisPatricia A. Wood, Rajen Mody, Lan Yi, Mimi Leung, Lamis K. Eldjerou, Carl H. June, Shannon L. Maude

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27 Scopus citations


Background Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T cell therapy, has demonstrated efficacy in children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) in two multicenter phase 2 trials (ClinicalTrials.gov, NCT02435849 (ELIANA) and NCT02228096 (ENSIGN)), leading to commercialization of tisagenlecleucel for the treatment of patients up to age 25 years with B-ALL that is refractory or in second or greater relapse. Methods A pooled analysis of 137 patients from these trials (ELIANA: n=79; ENSIGN: n=58) was performed to provide a comprehensive safety profile for tisagenlecleucel. Results Grade 3/4 tisagenlecleucel-related adverse events (AEs) were reported in 77% of patients. Specific AEs of interest that occurred ≤8 weeks postinfusion included cytokine-release syndrome (CRS; 79% (grade 4: 22%)), infections (42%; grade 3/4: 19%), prolonged (not resolved by day 28) cytopenias (40%; grade 3/4: 34%), neurologic events (36%; grade 3: 10%; no grade 4 events), and tumor lysis syndrome (4%; all grade 3). Treatment for CRS included tocilizumab (40%) and corticosteroids (23%). The frequency of neurologic events increased with CRS severity (p<0.001). Median time to resolution of grade 3/4 cytopenias to grade ≤2 was 2.0 (95% CI 1.87 to 2.23) months for neutropenia, 2.4 (95% CI 1.97 to 3.68) months for lymphopenia, 2.0 (95% CI 1.87 to 2.27) months for leukopenia, 1.9 (95% CI 1.74 to 2.10) months for thrombocytopenia, and 1.0 (95% CI 0.95 to 1.87) month for anemia. All patients who achieved complete remission (CR)/CR with incomplete hematologic recovery experienced B cell aplasia; however, as nearly all responders also received immunoglobulin replacement, few grade 3/4 infections occurred >1 year postinfusion. Conclusions This pooled analysis provides a detailed safety profile for tisagenlecleucel during the course of clinical trials, and AE management guidance, with a longer follow-up duration compared with previous reports.

Original languageEnglish
Article number002287
JournalJournal for ImmunoTherapy of Cancer
Issue number8
StatePublished - 5 Aug 2021


  • chimeric antigen
  • hematologic neoplasms
  • pediatrics
  • receptors


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