The outcome of high risk stage III melanoma patients (pts) is poor, with a 5-year overall survival (OS) rate of < 50%. Adjuvant (adj) high dose IPI , adj NIVO and pembrolizumab improved RFS. Neo-adjuvant (neoadj) treatment may be an even more favorable approach as immune checkpoint inhibition is of greatest value at the moment of TCR triggering and therefore dependent on the amount of antigen present. In our previous phase Ib OpACIN study the pathological RR (pRR) was 78% in the neoadj arm, and to date after 25 months of median follow-up none of the responders has relapsed. This raises the question whether such pts need to undergo complete lymph node dissection (CLND). A prerequisite for such an approach would be an analysis method that reliably indicates pathological response within the whole lymph node bed, without the need for CLND.
To address this question an in-house developed magnetic marker was placed ultrasound-guided at baseline into the largest regional lymph node metastasis of pts participating in OpACIN-neo, (NCT02977052), a phase 2 trial aiming at identification of the optimal neoadj combination scheme of IPI and NIVO in stage IIIB/C melanoma pts followed by CLND.
So far, 11 pts participated in this side trial of OpACIN-neo. No complications from marker placing were observed, and all magnetic markers were retrieved during the CLND after 6 weeks of neoadj IPI+NIVO. 10/11 marked lymph-nodes (LN were representative in their response for the whole CLND specimen, i.e. index node showed a complete or partial response (PR), all others on CLND showed the same or better responses. Only 1 case was incongruent, as the index LN had 60% vital tumor (no response) compared to another LN (40% vital tumor, PR).
Our early exploratory data from this pilot study indicate that marked LN in stage III melanoma could serve as response indicators for the outcome of the whole CLND after neoadj IPI+NIVO. If confirmed, our data can open the path towards response-driven extent of lymph-node dissection in macroscopic stage III melanoma.
Clinical trial identification
Legal entity responsible for the study
Alexander C.J. van Akkooi.
Has not received any funding.
A.C.J. van Akkooi: Consulting or advisory: Amgen, Novartis, MSD Oncology, Merck; Travel, accommodations, expenses: Amgen, Roche, Novartis; Research funding: Amgen, Novartis. C.U. Blank: Personal fees, Advisory role: MSD, BMS, Roche, GSK, Novartis, Pfizer, Lilly; Grants: BMS, Novartis, outside the submitted work. All other authors have declared no conflicts of interest.