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

Abstract

e14024 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.