RT Journal Article SR Electronic T1 Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma: Intent-to-Treat Analysis and Efficacy after Failure to Prior Immunotherapies JF Clinical Cancer Research JO Clin Cancer Res FD American Association for Cancer Research SP 4792 OP 4800 DO 10.1158/1078-0432.CCR-13-0380 VO 19 IS 17 A1 Besser, Michal J. A1 Shapira-Frommer, Ronnie A1 Itzhaki, Orit A1 Treves, Avraham J. A1 Zippel, Douglas B. A1 Levy, Daphna A1 Kubi, Adva A1 Shoshani, Noa A1 Zikich, Dragoslav A1 Ohayon, Yaara A1 Ohayon, Daniel A1 Shalmon, Bruria A1 Markel, Gal A1 Yerushalmi, Ronit A1 Apter, Sara A1 Ben-Nun, Alon A1 Ben-Ami, Eytan A1 Shimoni, Avichai A1 Nagler, Arnon A1 Schachter, Jacob YR 2013 UL http://clincancerres.aacrjournals.org/content/19/17/4792.abstract AB Purpose: Adoptive cell transfer (ACT) using autologous tumor-infiltrating lymphocytes (TIL) was reported to yield objective responses in about 50% of metastatic patients with melanoma. Here, we present the intent-to-treat analysis of TIL ACT and analyze parameters predictive to response as well as the impact of other immunotherapies. Experimental Design: Eighty patients with stage IV melanoma were enrolled, of which 57 were treated with unselected/young TIL and high-dose interleukin-2 (IL-2) following nonmyeloablative lymphodepleting conditioning. Results: TIL cultures were established from 72 of 80 enrolled patients. Altogether 23 patients were withdrawn from the study mainly due to clinical deterioration during TIL preparation. The overall response rate and median survival was 29% and 9.8 months for enrolled patients and 40% and 15.2 months for treated patients. Five patients achieved complete and 18 partial remission. All complete responders are on unmaintained remission after a median follow-up of 28 months and the 3-year survival of responding patients was 78%. Multivariate analysis revealed blood lactate-dehydrogenase levels, gender, days of TIL in culture, and the total number of infused CD8+ cells as independent predictive markers for clinical outcome. Thirty-two patients received the CTLA-4-blocking antibody ipilimumab prior or post TIL infusion. Retrospective analysis revealed that nonresponders to ipilimumab or IL-2 based therapy had the same overall response rate to ACT as other patients receiving TIL. No additional toxicities to TIL therapy occurred following ipilimumab treatment. Conclusion: Adoptive transfer of TIL can yield durable and complete responses in patients with refractory melanoma, even when other immunotherapies have failed. Clin Cancer Res; 19(17); 4792–800. ©2013 AACR.See related article by Yee, p. 4550