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 human leukocyte antigens. The US Food and Drug Administration (FDA) recently approved commercial TIL (lifileucel [Amtagvi]) for treatment of BRAF wild-type/resistant, checkpoint inhibitor failure, unresectable or metastatic melanoma based on a 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 for patients with melanoma referred for TIL therapy.

METHODS

A retrospective analysis of the cell therapy database of outcomes in 45 patients with unresectable or metastatic melanoma referred for TIL therapy considerations is reported.

RESULTS

The median age of the patients was 68 years (range, 27-83); 37 (82.2%) had stage IV and 38 (84.4%) had BRAF wild-type disease, and 15 (33.3%) had central nervous system disease. Twenty-three 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 lymphodepleting (LD) chemotherapy at the time of data analysis. Three patients died from disease progression, and 1 went on comfort care prior to starting LD chemotherapy. Eight (28.5%) TIL products were out of specification. Seventeen referred patients did not proceed to tumor resection: 8 (47.1%) were deemed ineligible owing to small tumor size (<1.5 cm), comorbidities, or nonresectable site/brain metastases; 3 had no definitive evidence of disease; 2 died due to rapid disease progression; and 3 deferred due to autoimmune colitis from prior checkpoint inhibitors and patient choice (n = 1). The median overall survival (mOS) for all patients who successfully pursued TIL therapy was not reached, with a 1-year OS of 79.2% (95% CI, 60.2%-100%) compared with patients who did not pursue TIL therapy, with a mOS of 10.15 months and a 1-year OS of 42% (95% CI, 23.4%-75.4%; P = 0.007; Figure 2). Workflow modifications were implemented as part of a quality improvement initiative after 6 months. Upon receipt of a TIL referral, consultation with the cellular therapy (CT) team was initiated, followed by an urgent referral to the surgical oncology team. 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 in 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 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.