Real-World, Evidence-Based, Retrospective Study of Patients Infused with Commercially Released Lifileucel for Advanced Melanoma.

Lifileucel is a tumor-derived autologous T-cell therapy approved by the US Food and Drug Administration for patients with advanced melanoma previously treated with an immune checkpoint inhibitor and, for BRAF V600-mutated disease, a BRAF ± MEK inhibitor. The real-world effectiveness of commercially available lifileucel has not yet been characterized. We conducted a retrospective study across four US centers of adults with metastatic melanoma treated with standard-of-care lifileucel per the US prescribing information. The primary objective was to evaluate real-world effectiveness based on treating physician-assessed objective response rate (ORR). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Preconditioning lymphodepletion was administered per institutional practice, followed by lifileucel infusion and up to six doses of interleukin-2 (IL-2; 600,000 IU/kg). Forty-three patients were included (median age 59 yr [range, 28 to 79]; 54% male); 44% had BRAF V600 mutations. Melanoma subtypes included cutaneous nonacral (70%), acral (9%), mucosal (19%), and unknown primary (2%); liver and treated brain metastases were present in 30% (n = 13) and 28% (n = 12), respectively. Patients received a median of three prior systemic anticancer therapies (range, 1 to 7). Prior to lymphodepletion, 44% received bridging therapy, which predominantly reflected continuation of prior targeted therapy. Following lifileucel infusion, patients received a median of five IL-2 doses (range, 1 to 6). Among 41 response-evaluable patients, physician-assessed ORR was 44% (n = 18), including complete response in 5% (n = 2) and partial response in 39% (n = 16). ORR was 52% among patients who received ≤2 prior lines of therapy (n = 23) and 33% among those who received ≥3 prior lines (n = 18). ORR was 58% among patients receiving ≤3 IL-2 doses (n = 12) and 38% among those receiving ≥4 doses (n = 29). With a median follow-up of 5.7 mo (95% confidence interval [CI], 1 to 15), median PFS and OS were 4.4 (95% CI, 2.8 to 8.9) and 10.2 mo (95% CI, 6.1 to NR), respectively. In this multicenter real-world cohort, commercially available lifileucel demonstrated meaningful clinical activity in patients with advanced melanoma, with outcomes comparable to pivotal trial results. Fewer prior lines of therapy and normal lactate dehydrogenase were associated with improved outcomes, supporting earlier consideration of tumor-infiltrating lymphocyte therapy in appropriate patients.