G. Gauvin1, K. Liang1, K. Ruth2, C. Mayemura1, E. McGillivray1, K. Loo1, A. Olszanski3, S. Movva3, M. Lango1, J. D’Souza5, H. Wu4, S. Reddy1, J. Farma1 1Fox Chase Cancer Center,Department Of Surgical Oncology,Philadelphia, PA, USA 2Fox Chase Cancer Center,Department Of Biostatistics,Philadelphia, PA, USA 3Fox Chase Cancer Center,Department Of Hematology/Oncology,Philadelphia, PA, USA 4Fox Chase Cancer Center,Department Of Pathology,Philadelphia, PA, USA 5Fox Chase Cancer Center,Molecular Therapeutics Program,Philadelphia, PA, USA
Introduction: Advanced melanoma treatment has significantly evolved in the past decade with the development of immunotherapy-derived treatments, and the approval of the first targeted immunotherapy in 2011. The goal of this study was to investigate the impact of the presence of tumor infiltrating lymphocytes in the primary tumor on patients’ response rate to targeted immunotherapies.
Methods: A retrospective chart review was conducted on patients diagnosed with melanoma at our tertiary center between 2011 and 2018. Patients who were treated with immunotherapy and in which tumor infiltrating lymphocytes (TILs) were positive or absent on the initial biopsy were included. Demographic and clinical data were collected and response to therapy was determined by Kaplan-Meier survival and Cox regression analyses.
Results: Twenty-seven patients (67% male) were included in this study. The median age was 58 (range 24-86) and the median follow-up time was 12.9 months. Patients were staged as stage II (n=1), stage III (n=22), and stage IV (n=4). Tumor infiltrating lymphocytes (TILs) were present (brisk or non-brisk) in 12 patients and absent in 15 patients. TILs present patients received anti-CTLA4 antibody (n=6) or PD-1 inhibitor (n=6). TILs absent patients received anti-CTLA4 antibody (n=7) or PD-1 inhibitor (n=8). Recurrence occurred in 3 of TILs present and 7 of TILs absent. Disease progression did not occur in the TILs present cohort but was seen in 2 of the TILs absent (their median PFS was 6.9 months). Death due to disease did not occur in TILs present, but was seen in 4 TILs absent (stage III n=2, stage IV n=2), all of whom were treated with anti-CTLA4 antibody. Two were free of disease, subsequently recurred, and were treated with combination anti-CTLA4 and PD-1 inhibitor (n=1) or just PD-1 inhibitor (n=1). Death due to other causes was seen in one patient from each group, both stage III and received ipilimumab. When comparing the TILs present and TILs absent groups, the median disease-free survival (DFS) was 16.9 months versus 10.5 months and overall survival (OS) was 15.9 months vs 11.9 months, respectively. Kaplan-Meier survival curves demonstrated that DFS was significantly higher in patients with TIL (p=0.04), but there was no significant difference in OS (p=0.25). Multivariate analysis using Cox regression model adjusting for age confirmed that the presence of TILs is associated with an increased DFS (p=0.05) (HR=0.114, 95%CI 0.013-1.029), but not for OS (p=0.12).
Conclusion: Immunotherapy has marked the beginning of a new era in treatment of advanced melanoma. In this pilot study, TIL has the potential to be a first screening tool to orient patients to these targeted treatments while waiting for genetic testing. We will continue to investigate this marker in larger studies.
