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

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.

• Authors: 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 Schlis, Patricia A Wood, Rajen Mody, Lan Yi, Mimi Leung, Lamis K Eldjerou, Carl H June, Shannon L Maude
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 9 Issue 8 (08 2021) ISSN: 2051-1426 [Electronic] England
• PMID: 34353848 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

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

Topics

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