Postdoctoral Research Fellow University of Pennsylvania, Perelman School of Medicine Philadelphia, Pennsylvania, United States
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Participants should be aware of the following financial/non-financial relationships:
Richard J. Straker, III, MD: Disclosure information not submitted.
Introduction: The prognostic role of tumor infiltrating lymphocytes (TILs) in melanoma has been variably reported; the impact of TILs on outcomes and treatment efficacy for patients in the contemporary era remains poorly characterized.
Methods: Consecutive patients who underwent wide excision and sentinel lymph node (SLN) biopsy for cutaneous melanoma >1.0mm thick at a single institution were identified (2006-2019). Patients were stratified based on primary tumor TIL status as brisk (bTILs), non-brisk (nbTILs) or absent (aTILs). Associations between patient factors and outcomes were analyzed using multivariable analysis, and 5-year outcomes were estimated.
Results: Of the 1,017 patients evaluated, 87 (8.6%) had bTILs and 759 (74.6%) had nbTILs. TILs presence was associated with significantly higher rates of regression (odds ratio [OR] 2.1, p=0.005), and significantly lower rates of acral lentiginous histology (OR 0.2, p=< 0.001) and SLN positivity (OR 0.6, p=0.038). Specifically, the SLN positivity rate for bTILs, nbTILs and aTILs was 8.1%, 17.0%, and 23.6%, respectively (p< 0.01). On multivariable analysis, no association was observed between disease-specific survival (DSS) and any-type TILs (hazard ratio [HR] 1.0, p=0.890), nbTILs (HR 1.0, p=0.870) or bTILs (HR 1.1, p=0.909). bTILs were associated with a significant recurrence free survival (RFS) advantage (bTILs [HR 0.5, p=0.048], nbTILs [HR 0.7, p=0.117), and with significantly improved 5-year RFS (84.0% bTILs vs. 71.8% nbTILs vs. 68.4% aTILs, log-rank p=0.048) (Figure 1). For the 110 patients immune checkpoint blockade (ICB) naïve patients who developed a melanoma recurrence that was treated with ICB therapy, no association was seen between progression-free survival and any-type TILs (HR 0.6, p=0.211), nbTILs (HR 0.6, p=0.182) or bTILs (HR 0.9, p=0.893).
Conclusions: The prognostic influence of primary TILs in the contemporary melanoma era appears complex, with association to regional metastasis and improved RFS, but not DSS. Moreover, in the setting of metastatic disease, primary TILs do not appear to confer predictive value to ICB responsiveness. Further studies characterizing TIL phenotype and their association with regional metastasis are warranted.
Learning Objectives:
Upon completion, participants will be able to list the factors associated with tumor infiltrating lymphocytes among a contemporary cohort of melanoma patients.
Upon completion, participants will be able to describe the associations between tumor infiltrating lymphocytes and disease-specific survival, recurrence-free survival, and progression-free survival among a contemporary cohort of melanoma patients.
Upon completion, participants will be able to understand the need for further studies characterizing tumor-infiltrating lymphocyte phenotype and investigating their association with regional metastases in the contemporary era.