TY  - JOUR
A1  - Levine, John E.
A1  - Grupp, Stephan
A1  - Pulsipher, Michael A.
A1  - Dietz, Andrew C.
A1  - Rives, Susana
A1  - Myers, G. Douglas
A1  - August, Keith J.
A1  - Verneris, Michael R.
A1  - Büchner, Jochen
A1  - Laetsch, Theodore W.
A1  - Bittencourt, Henrique
A1  - Baruchel, Andre
A1  - Boyer, Michael W.
A1  - De Moerloose, Barbara
A1  - Qayed, Muna
A1  - Davies, Stella M.
A1  - Phillips, Christine L.
A1  - Driscoll, Timothy A.
A1  - Bader, Peter
A1  - Schlis, Krysta
A1  - Wood, Patricia A
A1  - Mody, Rajen
A1  - Yi, Lan
A1  - Leung, Mimi
A1  - Eldjerou, Lamis K.
A1  - June, Carl H.
A1  - Maude, Shannon L
T1  - Pooled safety analysis of tisagenlecleucel in children and young adults with B cell acute lymphoblastic leukemia
T2  - Journal for ImmunoTherapy of Cancer
N2  - 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.
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62985
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-629858
SN  - 2051-1426
N1  - Data are available on reasonable request. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
N1  - PAW is deceased.
N1  - These studies and writing assistance were funded by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. Representatives of the sponsor participated in study design, collection, data interpretation, and development/submission of the manuscript.
VL  - 9.2021
IS  - 8, art. e002287
SP  - 1
EP  - 12
PB  - BioMed Central
CY  - London
ER  -