1123P - Baseline tumor-infiltrating lymphocytes and response to immune checkpoint inhibition in advanced melanoma

Background

Although the presence of tumor-infiltrating lymphocytes (TILs) in pathological specimens has been associated with prolonged survival in melanoma, it is largely unknown whether TILs can predict response to immune checkpoint inhibition (ICI) in advanced melanoma. Therefore, we investigated the association between treatment response and TILs in the largest cohort to date.

Methods

Patients who received first-line anti-PD1 ± anti-CTLA4 for advanced cutaneous melanoma were retrospectively identified from nine hospitals in the Netherlands. TILs were scored as absent, non-brisk or brisk on hematoxylin and eosin (H&E) slides of primary melanoma and pre-treatment metastases. The primary outcome was clinical response to ICI according to RECIST 1.1. Univariable and multivariable logistic regression analyses were performed and Kaplan-Meier methods were used for survival analyses.

Results

Metastatic melanoma specimens were available for 676 patients, whereas primary melanomas were available from 436 patients. TILs were absent in 347, non-brisk in 260 and brisk in 69 metastases. Compared to patients with absent TILs, both patients with non-brisk TILs (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.25-2.43) and brisk TILs (OR 3.58, 95%CI 2.01-6.64) had a higher probability of response to ICI. This association remained in multivariable analysis, adjusted for age, sex, disease stage, lactate dehydrogenase level and World Health Organisation performance score (see table). Patients with absent TILs had a shorter median progression-free survival (PFS) compared to patients with non-brisk TILs and brisk TILs (6.2, 10.6 and 19.3 months, respectively [p=0.003]). No significant association was found between TILs in primary melanoma specimens and response. Table: 1123P

Objective response rate (ORR), odds ratio (OR) and adjusted OR for response, median progression-free survival (PFS) and overall survival (OS) in months, stratified by TIL score on 676 pre-treatment metastatic specimens of advanced melanoma patients treated with ICI

Conclusions

The presence of non-brisk and brisk TILs in pre-treatment metastatic H&E histopathology specimens is associated with better response to ICI and survival outcomes.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Hanarth Fonds.

Disclosure

M. Labots: Financial Interests, Institutional, Advisory Role: Bristol Myers Squibb, Janssen-Cilag B.V. K.P.M. Suijkerbuijk: Financial Interests, Institutional, Advisory Board: Novartis, BMS, AbbVie, Pierre Fabre, MSD; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Research Grant: Novartis, TigaTx. All other authors have declared no conflicts of interest.