Real World Clinical Outcomes in Melanoma Patients Treated at a Single-Center Tumor Infiltrating Lymphocyte (TIL) Therapy Program using commercial Lifileucel.

[BACKGROUND] Tumor infiltrating lymphocyte (TIL) therapy entails isolating, activating, expanding, and reinfusing isolated lymphocytes from tumors, presumably representing a collection of high affinity T cells that can recognize the melanoma tumor specific peptides expressed on endogenous HLA antigens. FDA recently approved Commercial TIL (Lifileucel; Amtagvi®), for treatment of BRAF wild type/resistant, checkpoint inhibitor failure, unresectable or metastatic melanoma, based on registrational trial showing an overall response rate of 31.5% in treated patients. Following FDA approval, patient outcomes beyond the originally selected clinical trial populations remain unknown.

[OBJECTIVE] We report initial real-world, single institutional observations and outcomes with melanoma referred for TIL therapy.

[METHODS] Retrospective analysis of cell therapy database of outcomes in 45 patients with unresectable or metastatic melanoma referred for TIL therapy considerations are reported.

[RESULTS] The median age was 68 years (27-83),37 (82.2%) had stage IV and 38 (84.4%) had BRAF wild-type disease, and 15 (33.3%) had CNS disease. 23 patients were male (51.1%), 28 (62.2%) patients completed surgical tumor harvest, 23(51.1%) patients completed TIL infusion, and 1 patient was just starting LD chemotherapy at the time of data analysis. 3 patients died from disease progression, and one went on comfort care prior to starting lymphodepleting chemotherapy. 8 (28.5%) TIL products were out of specification. 17 referred patients did not proceed to tumor resection: 8 (47.1%) were deemed ineligible due to small tumor size (<1.5 cm), co-morbidities or nonresectable site/brain mets,3 had not definitive evidence of disease, 2 died due to rapid disease progression, 3 deferred due to autoimmune colitis from prior CPI, and pt choice (n=1). The median overall survival for all patients who successfully pursued TIL therapy was not reached with 1-year OS of 79.2% (95% CI 60.2% to 100%) compared to patients who did not pursue TIL therapy with a mOS of 10.15 months and with 1-year OS of 42% (95% CI 23.4% to 75.4%) [p 0.007] (Fig. 2). Workflow modifications were implemented as part of a quality improvement initiative after six months. Upon receipt of a TIL referral, consultation with the Cellular Therapy (CT) team was initiated, followed by an urgent referral to Surgical Oncology. A CT nurse served as the central point of contact, coordinating all subsequent encounters, including operating room scheduling, tumor collection, CT laboratory processing, and industry partner manufacturing slot allocation. Table 2 demonstrates a reduction of the average time interval between referral and CT consult (17.6 vs 10.7 days with the new workflow), and a time interval between initial referral and receiving actual TIL infusion (128 days vs 96.3 days).

[CONCLUSIONS] Our institutional real-world data show that only about half of TIL therapy referrals will proceed with the actual TIL infusions. While TIL therapy seeks to achieve the approximately 32% response rate observed in the registrational trial, real-world outcomes in an intent-to-treat population are anticipated to be inferior. Advanced melanoma affords a narrow time window from referral to completion of TIL manufacturing and infusion, necessitating efficient workflows to enable early treatment and optimize patient outcomes.