无需淋巴细胞清除方案的有效 TIL 疗法治疗检查点抑制剂耐药黑色素瘤需 IFNα

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 IFN 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 .

The treatment was safe, and side effects included IFN -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 , clearly suggesting the need for IFN support. IFN 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 IFN 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.