Treatment with tumor-infiltrating lymphocytes in the changing treatment landscape of metastatic melanoma.

person Troels Borch Center for Cancer Immune Therapy, Department of Hematology and Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark info_outline Troels Borch, Rikke Andersen, Eva Ellebaek, Özcan Met, Marco Donia, Inge Marie Svane

Authors person Troels Borch Center for Cancer Immune Therapy, Department of Hematology and Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark info_outline Troels Borch, Rikke Andersen, Eva Ellebaek, Özcan Met, Marco Donia, Inge Marie Svane Organizations Center for Cancer Immune Therapy, Department of Hematology and Department of Oncology, Herlev Hospital, University of Copenhagen, Herlev, Denmark, Department of Oncology and Center for Cancer ImmuneTherapy, Department of Hematology, Copenhagen University Hospital Herlev, Herlev, Denmark Abstract Disclosures Research Funding Other Foundation Capital Region of Denmark Background: Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) has been shown to induce durable complete responses in patients with metastatic melanoma (MM) who are anti-PD-1 naïve. Whether progression on or after anti-PD-1 therapy affects the outcome of TIL therapy given as a subsequent treatment line is largely unknown. To elucidate this, we analyzed updated clinical data covering a decade of TIL trials carried out in Denmark. Methods: Data from three clinical trials were pooled and data from 55 treated patients were available (ClinicalTrials.gov Identifiers: NCT00937625 (n = 31), NCT02379195 (n = 12) and NCT02354690 (n = 12)). Survival curves were computed according to the Kaplan-Meier method. Clinical response rate (RR) was evaluated according to RECIST criteria. Results: Median overall survival in the pooled cohort was 15.9 months and progression-free survival (PFS) was 3.7 months. Six patients achieved a complete response (11%), of which four are ongoing. Fourteen patients achieved a partial response (26%), of which three are ongoing. Median overall survival of responders was not reached with a median follow-up time of 40 months. RR was not statistically different depending on prior anti-PD-1 therapy (42% no prior anti-PD-1 therapy vs. 32% with prior anti-PD-1 therapy). However, there was a trend towards a shorter duration of partial responses in patients previously treated with both anti-CTLA-4 monotherapy and anti-PD-1 monotherapy, compared to patients previously treated with anti-CTLA-4 but not anti-PD-1 (P = 0.06). The two groups were balanced in respect to number of prior treatment lines. Conclusions: After progression on anti-PD-1 therapy, partial responses following TIL therapy might be shorter, but durable complete responses can be induced despite progression on prior anti-PD-1 therapy. Thus, TIL therapy remains an important treatment strategy in MM. Clinical trial information: NCT00937625, NCT02379195, NCT02354690