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Adoptive cell therapy with tumor-infiltrating lymphocytes in combination with nivolumab in patients with advanced melanoma

Authors :
D. König
B. Kasenda
M. Sandholzer
A. Chirindel
A. Zingg
R. Ritschard
H. Thut
K. Glatz
E.A. Kappos
D. Schaefer
C. Kettelhack
J. Passweg
K. Baur
A. Holbro
A. Buser
D. Lardinois
L.T. Jeker
N. Khanna
F. Stenner
M.S. Matter
N. Rodrigues Mantuano
M. Binder
A. Zippelius
H. Läubli
Source :
Immuno-Oncology and Technology, Vol 24, Iss , Pp 100728- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Background: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a personalized immunotherapy. The efficacy of TIL-ACT has been demonstrated prospectively in patients with advanced melanoma but is not limited to melanoma patients. Many patients are refractory to TIL-ACT, however, or their cancer becomes resistant. Combining anti-programmed cell death protein 1 (anti-PD-1) with TIL-ACT to antagonize the immunosuppressive tumor microenvironment may synergize to enhance the antitumor potential. Material and methods: We set up the BaseTIL trial (NCT04165967), a single-center investigator-initiated phase I trial, to test feasibility and safety of TIL-ACT followed by PD-1 blockade in patients with advanced cutaneous melanoma with disease progression after at least one line of anti-PD-1. TIL-ACT included tumor collection, ex vivo TIL expansion, lymphodepletion with cyclophosphamide and fludarabine, TIL transfer, and in vivo TIL stimulation with interleukin 2 (125 000 IU/kg, 10 days). TIL-ACT was followed by nivolumab treatment for a maximum of 2 years. Nine patients were planned for inclusion. Results: Between 2020 and 2022, we enrolled 11 patients and 9 underwent a TIL transfer (median transfused cell number: 66.25 × 109). Two patients did not start lymphodepletion. Nine patients received at least 1 dose of interleukin 2 (median number: 10; range, 1-10), seven started nivolumab (median number: 5; range, 2-23). All patients had hematologic adverse events (AEs). Most common non-hematologic AEs were fever and cytokine release syndrome. No nivolumab-associated AEs of ≥ grade 2 occurred. The objective response rate to TIL-ACT was 22% (2/9, 2 partial remission). Conclusions: TIL-ACT with nivolumab is feasible and safe. Larger trials are needed to further determine the efficacy of this combination.

Details

Language :
English
ISSN :
25900188
Volume :
24
Issue :
100728-
Database :
Directory of Open Access Journals
Journal :
Immuno-Oncology and Technology
Publication Type :
Academic Journal
Accession number :
edsdoj.77a15df7af5480ea93dda0ce4aa25e6
Document Type :
article
Full Text :
https://doi.org/10.1016/j.iotech.2024.100728