One-time 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 nonmucosal 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 TIL (tumor infiltrating lymphocyte) cell therapy that uses TILs recovered from a patient’s tumor tissue to produce billions of polyclonal patient-specific TILs during a 22-day centralized manufacturing process. Recently, results of the phase 2 trial C-144-01 (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 of the Masonic Cancer Center, Minneapolis, reported results from a subgroup of participants with advanced mucosal melanoma (n=12).4 The median age of patients was 61 years, the median number of prior therapies was 2 (range, 1-6), and all participants were BRAFV600 wildtype. The median dose of lifileucel was 26.1×109 cells. All patients had a high disease burden.
After a median follow-up of 35.7 months, ORR was 50% (95% CI, 21.1%-78.9%), 1 patient had a complete response, and 5 patients 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, participants with mucosal melanoma had a low tumor 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-hematological adverse events in grades 3-4 were febrile neutropenia (58.3%) and hypotension (33.3%). All participants presented with hematological adverse events in grades 3-4, as was to be expected after the non-myeloablative lymphodepletion required for TIL harvest for lifileucel manufacturing.
Dr. Domingo-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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