Effective TIL Therapy for Patients with Checkpoint-Resistant Melanoma without Lymphodepleting Regimens Requires IFNα.

Abstract

Patients with melanoma progressing on immune checkpoint blockade may benefit from adoptive transfer of tumor-infiltrating lymphocytes (TIL). We investigated the impact of a pegylated IFNα conditioning and support regimen on the safety and efficacy of TIL plus nivolumab (NCT03638375). Patients with immune checkpoint blockade-resistant stage III/IV melanoma were treated with TIL plus nivolumab without (n = 9) or with (n = 25) IFNα. The treatment was safe, and side effects included IFNα-induced lymphopenia (16%) and neutropenia (12%). No febrile neutropenia or >grade 4 adverse events were observed. Disease control was obtained in 11.1% (95% confidence interval, -14.5%-36.7%) of the patients treated without and in 41.7% (95% confidence interval, 20.4%-62.9%) of the patients treated with IFNα, clearly suggesting the need for IFNα support. IFNα treatment strongly reduced the numbers of circulating leukocytes and neutrophils, more consistently in therapy responders. No differences were observed in the phenotype and dose of TIL administered. Taken together, our low-toxicity therapy comprising TIL, nivolumab, and IFNα is safe, shows evidence of clinical activity, and may be particularly suitable for more frail patients who are less able to tolerate lymphodepletion and high-dose IL-2 regimens.