1090P High concurrent interferon gamma signature expression in the primary tumor and lymph node metastasis is associated with superior outcome upon neoadjuvant ipilimumab + nivolumab in stage III melanoma

Hoeijmakers L, Dimitriadis P, Cornelissen S, Reijers I, van de Wiel B, Scolyer RA, Saw RPM, Spillane AJ, Broeks A, Lopez-Yurda M, Grijpink-Ongering L, Hospers G, Menzies AM, van Akkooi ACJ, Van Houdt W, Long GV, Blank CU. Annals of Oncology, 35(Sep 24 2024): S721-S22, doi:10.1016/j.annonc.2024.08.1158.

Background

The interferon gamma gene signature (IFNg) has been shown to be predictive and prognostic in patients (pts) with macroscopic stage III or IV melanoma. In macroscopic stage III melanoma, IFNg from lymph node biopsies (LN-IFNg) might be used in the future for neoadjuvant treatment decisions (combination vs monotherapy). To address the question of whether the IFNg can be analyzed using primary tumor material (P-IFNg) instead of LN-IFNg or, in the case of incongruencies, has a higher predictive value when combined with LN-IFNg, we analyzed the IFNg signature in paired samples (P and LN) from stage III melanoma pts.

Methods

Paraffin primary tumor tissue from pts with stage III melanoma, treated in the OpACIN-neo, PRADO and DONIMI trials (neoadjuvant anti-PD1 +/- anti-CTLA4 +/- domatinostat), was retrospectively analyzed with the nanostring nCounter PanCancer immune profiling panel and compared to fresh frozen LN biopsies. The cut-off was calculated based on event-free survival (EFS) using maximally selected rank statistics.

Results

Forty-four pts were included: the majority had a superficial spreading melanoma (68%), with a median Breslow thickness of 1.9mm (IQR: 1.1–2.9), ulceration of 23% and 57% had a BRAF mutation. The median time from primary tumor to trial registration was 21.8 months (IQR: 8.1-48.0). P-IFNg had a low correlation with LN-IFNg (r=0.33, p=0.03). High P-IFNg showed significantly prolonged DMFS and the same trend for EFS, RFS and OS (Table). Pts with concurrent high P- and LN-IFNg had 3 year-EFS of 95% as compared to 88% for pts with LN-IFNg high only, suggesting that addition of P-IFNg could improve selection of pts with better outcomes.

Conclusions

Our results suggest that pts with concurrently high IFNg–signature expressions (high IFNg in P and LN) have a better outcome than LN-IFNg high pts only. If confirmed, these findings could inform treatment selection and prognosis.