Effective TIL Therapy for patients with checkpoint-resistant melanoma without lymphodepleting regimens requires IFNα

Abstract

Purpose: Patients with melanoma progressing on immune checkpoint blockade may benefit from adoptive transfer of tumor-infiltrating lymphocytes (TIL).

Patients and Methods: We investigated the impact of a pegylated IFN alpha 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) IFN alpha.

Results: The treatment was safe, and side effects included IFN alpha-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 IFN alpha, clearly suggesting the need for IFN alpha support. IFN alpha 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. Conclusions: Taken together, our low-toxicity therapy comprising TIL, nivolumab, and IFN alpha 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.