Tumor mutational burden (TMB) in immune checkpoint inhibitor (ICI)-naïve and -experienced patients with metastatic melanoma treated with lifileucel, a tumor-infiltrating lymphocyte (TIL) cell therapy
Abstract
9524 Background: Cutaneous melanoma is characterized by high TMB, which is associated with increased tumor-specific neoantigen expression (Schumacher Science 2015) and an increased response rate to ICI (Yarchoan NEJM 2019). The TMB in tumors that recur/progress after ICI is not well defined. Lifileucel is a one-time, autologous TIL cell therapy under investigation for treatment of patients (pts) with advanced melanoma. We conducted a matched case-control study of prospectively enrolled pts with advanced melanoma treated with lifileucel in the ICI-naïve (IOV-COM-202 trial, Cohort 1A [C1A]) and post-ICI (C-144-01 trial, Cohort 2 [C2]) setting to investigate the potential association between prior ICI therapy, TMB, and response to lifileucel. Methods: All pts had unresectable or metastatic melanoma. Available cases from C1A (ICI-naïve pts receiving lifileucel + pembrolizumab [pembro]) were matched to controls from C2 (pts receiving lifileucel alone after progression on antiPD-1/PD-L1 therapy); 3 controls per case were matched at least for BRAF status and disease stage at study entry, and if possible, for anatomic site of tumor harvest. Lifileucel regimen was similar in C1A and C2. In C1A, 1 dose of pembro was given after tumor harvest and before nonmyeloablative lymphodepletion and resumed after lifileucel per standard treatment, for up to 2 y. Objective response rate (ORR) was assessed by investigators per RECIST v1.1. TMB of the resected tumor was measured using the ImmunoID…
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Evidence Hub reads this as a case-control, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause.
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