Comprehensive single institute experience with melanoma TIL: Long term clinical results, toxicity profile, and prognostic factors of response

Michal J. Besser, Orit Itzhaki, Guy Ben-Betzalel, Douglas B. Zippel, Dragoslav Zikich, Adva Kubi, Karin Brezinger, Abraham Nissani, Michal Levi, Li at Zeltzer, Alon Ben-Nun, Nethanel Asher, Avichai Shimoni, Arnon Nagler, Gal Markel, Ronnie Shapira-Frommer, Jacob Schachter

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Abstract: Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) mediates objective responses in 30% to 50% of patients with metastatic melanoma according to multiple, small phase 2 trials. Here we report the long-term clinical results, intent-to-treat analysis, predictors of response and toxicity profile in a large patient cohort. A total of 179 refractory melanoma patients were enrolled in the ACT trial. TIL were administered in combination with high-dose bolus interleukin-2 following preconditioning with cyclophosphamide and fludarabine. Patients were followed-up for a median of 7.2 years. A total of 107 (60%) of 179 enrolled patients were treated. The main reason for the drop out of the study was clinical deterioration. Of 103 evaluated patients, 29 patients (28%) achieved an objective response (OR), including complete remission (8%) or partial response (20%). Sixteen pateints exhibited stable disease. Predictors of response were performance status, time of TIL in culture and CD8 frequency in the infusion product. The absolute lymphocyte count 1 and 2 weeks after TIL infusion was the most predictive parameter of response. With a medium follow-up time of 7.2 years, OR patients reached a median overall survival (OS) of 58.45 months and a median progression-free survival (PFS) of 15.43 months, as compared with nonresponders, with 6.73 months OS and 2.60 months PFS. By 6 years, 50% of OR patients were alive and 43% had no documented progression. TIL ACT can yield durable objective responses, even as salvage therapy in highly advanced metastatic melanoma patients.

Original languageEnglish
Pages (from-to)736-744
Number of pages9
JournalMolecular Carcinogenesis
Volume59
Issue number7
DOIs
StatePublished - 1 Jul 2020
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020 Wiley Periodicals LLC

Funding

We would like to thank the Lemelbaum family for their generous support as well as, Rina Sarely, Sivan Ofir and Marina Gorodner for her expert technical assistance. The study was funded by the Lemelbaum family.

FundersFunder number
Lemelbaum family

    Keywords

    • adoptive cell therapy
    • clinical trial
    • immuno oncology

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