TY - JOUR
T1 - Comprehensive single institute experience with melanoma TIL
T2 - Long term clinical results, toxicity profile, and prognostic factors of response
AU - Besser, Michal J.
AU - Itzhaki, Orit
AU - Ben-Betzalel, Guy
AU - Zippel, Douglas B.
AU - Zikich, Dragoslav
AU - Kubi, Adva
AU - Brezinger, Karin
AU - Nissani, Abraham
AU - Levi, Michal
AU - Zeltzer, Li at
AU - Ben-Nun, Alon
AU - Asher, Nethanel
AU - Shimoni, Avichai
AU - Nagler, Arnon
AU - Markel, Gal
AU - Shapira-Frommer, Ronnie
AU - Schachter, Jacob
N1 - Publisher Copyright:
© 2020 Wiley Periodicals LLC
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
KW - adoptive cell therapy
KW - clinical trial
KW - immuno oncology
UR - http://www.scopus.com/inward/record.url?scp=85082962133&partnerID=8YFLogxK
U2 - 10.1002/mc.23193
DO - 10.1002/mc.23193
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C2 - 32250515
AN - SCOPUS:85082962133
SN - 0899-1987
VL - 59
SP - 736
EP - 744
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
IS - 7
ER -