Long-Term Efficacy and Safety of Lifileucel Tumor-Infiltrating Lymphocyte Cell Therapy in Patients With Advanced Melanoma: A 5-Year Analysis of the C-144-01 Study

Abstract

Patients with advanced melanoma resistant to immune checkpoint or BRAF/MEK inhibitors have treatment options with relatively low efficacy. Lifileucel, a one-time autologous tumor-infiltrating lymphocyte cell therapy, was approved in the United States on the basis of the pivotal C-144-01 study. A 5-year follow-up of the C-144-01 trial assessed the long-term efficacy and safety of lifileucel. At the cutoff date (November 20, 2024), the objective response rate was 31.4% (complete response [CR], 5.9%; partial response [PR], 25.5%). Overall, 79.3% of patients had tumor burden reduction; 16 had deepened responses with four converting from PR to CR > 1 year after lifileucel infusion; 31.3% of responders completed the 5-year assessment with ongoing responses. The median duration of response was 36.5 months. Responders (n = 48) had lower tumor burden and fewer liver or brain metastases than the overall population. The median overall survival (OS) was 13.9 months, with a 5-year OS of 19.7%. Adverse events were consistent with nonmyeloablative lymphodepletion and interleukin-2 safety profiles and declined rapidly within 2 weeks after lifileucel infusion. Most grade 3/4 cytopenias resolved to grade ≤2 by day 30. This 5-year analysis demonstrated long-term benefit and meaningful OS with one-time lifileucel therapy, with no additional long-term safety concerns.

FIG 1.

Patient disposition. Four patients underwent tumor harvest but NMA-LD was not administered because of death (cohort 2, n = 1; cohort 4, n = 3). One patient in cohort 2 was administered NMA-LD but lifileucel was not infused because of death. ^aPatients subsequently died due to progressive disease. ^bDeaths due to adverse events unrelated to any component of the lifileucel regimen include septic shock (n = 1), failure to thrive (n = 2), cerebral hemorrhage (n = 1), multiple organ dysfunction syndrome (n = 1), pulmonary embolism (n = 1), and intracranial hemorrhage (n = 1); death due to treatment-related adverse events include pneumonia related to NMA-LD and IL-2 administration (n = 1), arrhythmia related to cyclophosphamide (n = 1), acute respiratory failure related to NMA-LD (n = 1), intra-abdominal hemorrhage related to all components of the lifileucel regimen (n = 1), and bone marrow failure related to all components of the lifileucel treatment regimen (n = 1). ^cOther causes of death were disease progression or metastatic melanoma (n = 5), death during sleep (n = 1), and unknown causes (n = 4). IL-2, interleukin-2; NMA-LD, nonmyeloablative lymphodepletion.

FIG 2.

Kaplan-Meier estimated DOR in patients who achieved CR or PR. Tick marks indicate censored patients. CR, complete response; DOR, duration of response; NR, not reached; PR, partial response.

FIG 3.

Time to response and time on efficacy assessment for confirmed responders. CR, complete response; PD, progressive disease; PR, partial response.