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

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

Keywords

  • adoptive cell therapy
  • clinical trial
  • immuno oncology

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