Lifileucel induces a durable response in heavily pretreated mucosal melanoma

In a subgroup analysis of the phase 2 C-144-01 study, the one-time treatment with lifileucel induces a strong and durable response in patients with advanced mucosal melanoma.

Advanced mucosal melanoma is rare and difficult to treat, with worse outcomes after anti-PD-1 therapy than non-mucosal melanoma [1,2]. In pooled analyses, the objective response rate (ORR) is about 20%, and the median overall survival (OS) is 11–16 months. Lifileucel is a one-time, autologous tumour infiltrating lymphocyte (TIL) cell therapy that uses TILs recovered from a patient’s tumour tissue to produce polyclonal patient-specific TILs during a 22-day centralised manufacturing process. Recently, results of the phase 2 C-144-01 trial (NCT02360579) showed an ORR of 31.4% in 153 heavily pretreated patients with advanced melanoma (all subtypes but uveal melanoma) after a single infusion of lifileucel [3]. Dr Evidio Domingo-Musibay (Masonic Cancer Center, MN, USA) reported results from a subgroup of 12 participants with advanced mucosal melanoma [4].

The median age of the participants was 61 years, the number of prior therapies ranged from 1–6, and all participants were BRAF^V600 wildtype. The median applied dose of lifileucel was 26.1 x 10⁹ cells. All participants had a high disease burden.

After a median follow-up of 35.7 months, ORR was 50% (95% CI 21.1–78.9), 1 participant had a complete response, and 5 participants presented with a partial response. The median duration of response was not yet reached. “The duration of response was more than 6 months in all responders, more than 12 months in 5 responders, and more than 24 months in 4 responders,” highlighted Dr Domingo-Musibay.

In contrast to the participants with cutaneous melanoma, the participants with mucosal melanoma had a low tumour mutational burden (2.145 mutations/Mb vs 10.47 mutations/Mb). TIL persistence was comparable in mucosal and cutaneous melanoma beyond month 12. The most common non-haematological adverse events of grade 3–4 were febrile neutropenia (58.3%) and hypotension (33.3%). All participants presented with haematological adverse events of grades 3–4, which was expected because of the non-myeloablative lymphodepletion required for TIL harvest for lifileucel manufacturing.

Dr Doming-Musibay explained: “These results further support the potential benefit of lifileucel as a one-time treatment, a feature that makes it different from other immunotherapies.”

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   1. D'Angelo SP, et al. J Clin Oncol. 2017;35(2):226–235.
   2. Hamid O, et al. Br J Cancer. 2018;119:670–674.
   3. Chesney J, et al. J Immunother Cancer. 2022;10(12):e005755.
   4. Domingo-Musibay E, et al. Lifileucel tumour-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with advanced mucosal melanoma after progression on immune checkpoint inhibitors (ICI): Results from the phase II C-144-01 study. Abstract 1086O, ESMO 2023, 20–24 October, Madrid, Spain.

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Posted on 19 December, 202319 December, 2023