Efficacy of TIL therapy in advanced cutaneous melanoma in the current immuno-oncology era: updated systematic review and meta-analysis

Background: Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL-ACT) has consistently shown efficacy in advanced melanoma. New results in the field provide now the opportunity to assess overall survival (OS) after TIL-ACT and to examine the effect of prior anti-programmed cell death protein 1/programmed death-ligand 1 [anti-PD-(L)1] therapy on its efficacy. Methods: A comprehensive search was conducted in PubMed up to 29 February 2024. Iota n this meta-analysis we focused on studies including high-dose interleukin 2, doubling the patient numbers from our previous meta-analysis conducted up to December 2018 and using OS as the primary endpoint. Objective response rate (ORR), complete response rate (CRR), and duration of response were secondary endpoints. Findings are synthesized using tables, Kaplan-Meier plots, and forest plots. Pooled estimates for ORR and CRR were derived from fixed or random effects models. Results: A total of 13 high-dose interleukin 2 studies were included in this updated meta-analysis, with OS information available for 617 patients. No difference was found in median OS between studies with prior anti-PD-(L)1 treatment {n = 238; 17.5 months [95% confidence interval (CI) 13.8-20.5 months]} and without [n = 379; 16.3 months (95% CI 14.2-20.6 months)] (log-rank P = 0.53). ORR was estimated to be 34% (95% CI 16%-52%) and 44% (95% CI 37%-51%), for the studies with and without prior anti-PD-(L)1, respectively. The pooled estimate for CRR was 10% for both groups. No statistically significant difference was observed between the two groups, either for ORR (P = 0.15) or CRR (P = 0.45). Conclusions: Prior anti-PD-(L)1 treatment has no effect on the clinical response or survival benefit from TIL-ACT in advanced cutaneous melanoma. The benefit of TIL therapy in the second-line setting is also present after anti-PD-(L)1 treatment. Our data reinforce the evidence that TIL-ACT should be considered as a treatment of choice in second line for metastatic melanoma patients failing anti-PD-(L)1 therapy.