Abstract 1055P
Background
The use of immune checkpoint therapies is being investigated in early-stage melanoma patients (pts). So far there is no definitive prognostic and/or predictive biomarker. The presence of tumor-infiltrating lymphocytes (TILs) has been associated with a better prognosis in several malignancies, including melanoma. Using a digital pathology approach, we intended to identify a cut-off based on the percentage of TILs (%TILs) as a prognostic factor in this setting.
Methods
We analyzed 655 H&E stainings of primary melanomas of pts diagnosed with stage I/II melanoma between January 2000 and December 2018 in the Center for Dermato-Oncology at the University of Tuebingen. We used the software QuPathv1.2 to perform semi-automated determination of %TILs and the R package Evaluate Cutpoints to identify the best cut-off for stratification. Our primary endpoint was relapse-free survival (RFS) defined as the time from the initial diagnosis to first local or distant metastasis.
Results
We identified 381 pts in stage I and 274 in stage II (n=655). The median follow-up time was 70 months [IQR 39-112]. The optimized TIL% cut-off of 11.37 defined two groups: low and high %TILs, respectively below and above 11.37. The 10-years RFS rate was 53% and 75% for the low and high %TILs groups, respectively (95%CI: 40-66 and 71-79). There was a statistically significant difference for RFS in the univariate (UV) Cox analysis between the two groups (p<0.0001; HR: 2.51 (95%CI: 1.67-3.78), favoring pts with high %TILs). This RFS difference was also statistically significant in the UV Cox analysis in stage II alone (p<0.0001; HR:2.45; 95%CI: 1.55-3.88), but not in stage I. In the multivariate Cox analysis including tumor thickness (pT), ulceration and %TILs, pT and ulceration remained significant, with a trend for significance in %TILs, (p<0.0001; HR: 1.26 (95%CI: 1.19-1.34); p=0.003; HR: 1.77; (95%CI: 1.22-2.58) and p=0.148; HR: 1.39 (95%CI: 0.89-2.18), respectively).
Conclusions
Stage I/II melanoma pts with high %TILs had a statistically significant improved RFS compared to pts with low %TILs. %TILs is an easily determinable and semi-automated parameter that could be used to identify pts who would benefit from adjuvant treatment or a more personalized follow-up.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
H. Niessner: Financial Interests, Institutional, Research Grant: Novartis. S. Forchhammer: Financial Interests, , Invited Speaker: Takeda Pharmaceuticals . I. Bonzheim: Financial Interests, Personal, Invited Speaker: Novartis, Bayer, Pfizer, Takeda, AstraZeneca ; Financial Interests, Personal, Advisory Board: BMS, Novartis. C. Garbe: Financial Interests, Personal, Advisory Board: Pierre Fabre, Pfizer, Amgen, MSD, Philogen; Financial Interests, Personal and Institutional, Advisory Board: BMS, Neracare, Novartis, Roche, Sanofi. L. Flatz: Financial Interests, , Research Grant: Swiss National Science Foundation, Swiss Cancer League, Hookipa Pharma, and Novartis Foundation ; Financial Interests, , Advisory Role: Novartis, Sanofi and Bristol-Myers Squibb. T. Eigentler: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Principal Investigator: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Principal Investigator: Novartis; Financial Interests, Personal, Advisory Board: Philogen; Financial Interests, Personal, Principal Investigator: Philogen; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Principal Investigator: BMS; Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Speaker’s Bureau: Amirall. D. Rimm: Financial Interests, , Advisory Role: AstraZeneca, Agendia, Amgen, BMS, Cell Signaling Technology, Cepheid, Danaher, Daiichi Sankyo, Navigate BP/Novartis, GSK, Konica Minolta, Merck, NanoString, PAIGE.AI, Perkin Elmer, Roche, Sanofi, Ventana, Ultivue; Financial Interests, , Funding, Fund research in David L. Rimm’s lab: Amgen, Cepheid, NavigateBP, NextCure, and Konica Minolta. T. Sinnberg: Financial Interests, Institutional, Research Grant: Novartis. T.M.S. Amaral: Financial Interests, Personal, Invited Speaker: CeCaVa; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Neracare; Financial Interests, Institutional, Funding: Sanofi; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Funding: Skyline-Dx; Non-Financial Interests, Member: Portuguese Society for Medical Oncology; Non-Financial Interests, Member: Portuguese Society of Medical Oncology - Young Oncologists Group. All other authors have declared no conflicts of interest.