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
Theresa Medina, Jason Chesney, Harriet M. Kluger, Omid Hamid, Eric D. Whitman, Mike Cusnir, Sajeve Thomas, Martin Wermke, Evidio Domingo‐Musibay, Giao Q. Phan, John M. Kirkwood, James Larkin, Jeffrey S. Weber, Friedrich Graf Finckenstein, Jeffrey Chou, Brian Gastman, Xiao Wu, Rana Fiaz, Amod A. Sarnaik, for the C-144-01 Investigators, Brendan D. Curti, Kevin Kim, Gregory A. Daniels, Melissa Wilson, Sylvia Lee, Igor Puzanov, Amy Harker-Murray, Theodore F. Logan, Jan C. Simon, Ioannis Thomas, Beatrice Schuler-Thurner, Rose K. C. Moritz, Jessica C. Hassel, Gotz Ulrich Grigoliet, Ana Arance, B. Rubio, Juan C. Rodríguez, Alfonso Berrocal, Miguel F. Sanmamed, Hendrik-Tobias Arkenau, Thomas Evans, Pippa Corrie, Stéphane Dalle, Christophe Bédane, Judit Oláh, Angela Orcurto
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.