Real-world experience with lifleucel, tumor selection, and dead-in therapy from a single-institution series.

Abstract

9536 Background: Lifileucel is the first approved cellular therapy for persons with metastatic melanoma after upfront treatment with immune checkpoint inhibitor(s) (ICIs) and BRAF-targeted therapy (if applicable). There is not an established consortium to centralize data surrounding procurement and outcomes. Until then we report a single institution series of lifileucel used in the real-world in patients (pts) with previously treated metastatic melanoma. We evaluate whether there are differences in outcomes based on tumor procurement sites, lead-in therapy, and presence of CNS metastases prior to being treated with lifileucel. In addition, for those with progressive disease (PD) will describe the pattern of progression after lifileucel. Methods: The University of Colorado and its affiliated hospital UCHealth became an authorized treatment center for TIL in November 2024. Between November 2024 and January 2026, tumor tissue procurement was completed on 27 patients diagnosed with a variety of melanoma subtypes, stages and received bridging therapy. 24 pts have been treated with lifileucel. All pts received prior combination ICIs and, if BRAF-V600mut, most received prior treatment with BRAF/MEK inhibitors. Results: 41.7% of pts treated with lifileucel have had at least partial response (PR) as best overall response (BOR). 12% of pts have had a complete response (CR) as BOR. 16.7% had an initial PR but then had PD within 3 mos. 37.5% of pts had PD as BOR. In regard to tumor procurement site, tumor sites were subcutaneous/superficial soft tissue, lymph node, or visceral locations. The response rate from subcutaneous tumors was 16.7%, the response rate from lymph node was 33.3% and the response rate from visceral sites was 42.3%. The response rate from a single tumor used for procurement was 27%. The response rate from combining multiple tumors from different sites was 46%. The most recent therapy prior to lifileucel included: 1) ipilimumab+nivolumab, (5 pts) with 40% response rate, 2) relatlimab+nivolumab, (8 pts) with 75% response rate, 3) anti-PD-1 monotherapy, (3 pts) with 66% response rate, 4) BRAF/MEK inhibitor, (5 pts) with no response to lifileucel. 10 pts had CNS lesions treated prior to lifileucel, 6 pts had CNS lesions treated after lifileucel infusion, 5 were treated with BRAF/MEK prior to receiving lifileucel. 4 pts had PR and 2 had CR of metastatic sites present prior to lifileucel but had PD within 3 mos to new visceral sites. Conclusions: From our single-institution series, using lymph node and visceral tumors for lifileucel generation is associated with higher overall response rate. Combining more than one tumor for lifileucel generation is also associated with higher overall response rate. There were 6 patients that had CNS progression after lifileucel but the majority had used BRAF/MEK prior to receiving lifileucel which raises question of what effect this has on lifileucel efficacy.