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

J Immunother Cancer. 2021 Aug;9(8):e002287. doi: 10.1136/jitc-2020-002287.

Abstract

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.

Keywords: chimeric antigen; hematologic neoplasms; pediatrics; receptors.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Receptors, Antigen, T-Cell / therapeutic use*

Substances

  • Antineoplastic Agents, Immunological
  • Receptors, Antigen, T-Cell
  • tisagenlecleucel

Associated data

  • ClinicalTrials.gov/NCT02435849
  • ClinicalTrials.gov/NCT02228096