Adoptive Transfer of Tumor Infiltrating Lymphocytes in Metastatic Melanoma Patients: Intent-to-Treat Analysis and Efficacy after Failure to Prior Immunotherapies
Mené sur 80 patients atteints d'un mélanome métastatique, cette étude évalue l'efficacité d'un transfert adoptif de lymphocytes infiltrant les tumeurs, en combinaison ou non avec l'ipilimumab
Purpose: Adoptive Cell Transfer (ACT) using autologous Tumor Infiltrating Lymphocytes (TIL) was reported to yield objective responses in about 50% of metastatic melanoma patients. 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 stage IV melanoma patients were enrolled, of which 57 were treated with Unselected/Young TIL and high-dose IL-2 following non-myeloablative 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 Altogether 23 patients were withdrawn from the study mainly due to clinical deterioration during TIL preparation.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 CTLA4 blocking antibody ipilimumab prior or post TIL infusion. Retrospective analysis revealed that non-responders to ipilimumab or IL-2 based therapy had the same overall response rate to ACT as other TIL patients. No additional toxicities to TIL therapy occurred following ipilimumab treatment. Conclusion: Adoptive transfer of TIL can yield durable and complete responses in refractory melanoma patients, even when other immunotherapies have failed.