Journal for ImmunoTherapy of Cancer (Aug 2021)

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

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

DOI
https://doi.org/10.1136/jitc-2020-002287
Journal volume & issue
Vol. 9, no. 8

Abstract

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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.