Comparable responses of melanoma at primary site and synchronous lymph node metastases upon neoadjuvant ipilimumab (IPI) and nivolumab (NIVO)

Background In stage III melanoma patients, adjuvant immune checkpoint inhibition (ICI) has shown to improve relapse free survival. However, preclinical and translational data suggest that neoadjuvant (neoadj) ICI might be more beneficial due to broader immune activation. In the OpACIN and OpACIN-neo trials with neoadj IPI+NIVO, high pathologic (path) response rates (pRR) were observed (78% and 77%, respectively). Furthermore, neoadj ICI could reduce tumor burden, making surgery less mutilating. In patients presenting with synchronous lymph node (LN) metastases, neoadj ICI might improve surgical resectability of both sites. To date, response of these primary melanoma lesions upon neoadj IPI+NIVO is not reported. Methods Here we report on four stage III melanoma patients with melanoma at the primary site and synchronous LN metastases that were treated with neoadj IP+NIVO. Results Four stage III melanoma patients were identified. In the OpACIN-neo trial, one patient treated with 2 courses IPI 1 mg/kg + NIVO 3 mg/kg showed a path partial response (33% viable tumor cells) in the in-scar recurrence and a complete response (CR) in the LN metastasis, and one patient treated with 2 courses IPI 3 mg/kg followed by 2 courses NIVO 3 mg/kg showed no pathological response in both the in-scar recurrence (60% viable tumor cells) and LN metastasis (59% vital tumor). In the PRADO extension cohort, one patient treated with 2 courses IPI 1 mg/kg + NIVO 3 mg/kg demonstrated a path CR in both the axillar LN metastases and the primary melanoma on digit 4 of his right hand, preventing finger amputation. The results of another PRADO patient with a large primary on the shoulder and axillar LN metastases are pending (expected June 2019). Conclusions Neoadjuvant IPI+NIVO induces comparable responses in LN metastases and at the primary melanoma location. In the light of the high LN response upon neoadj IPI+NIVO, postponing the resection of the primary or recurrent melanoma should be considered, improving surgical resectability and reducing morbidity. Clinical trial identification NCT02977052. Legal entity responsible for the study Netherlands Cancer Institute. Funding BMS. Disclosure E.A. Rozeman: Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: NanoString. A.C.J. van Akkooi: Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: MSD Merck; Advisory / Consultancy: Merck-Pfizer; Advisory / Consultancy: 4SC. G.V. Long: Advisory / Consultancy: Aduro; Advisory / Consultancy: Amgen; Advisory / Consultancy: BMS; Advisory / Consultancy: Merck MSD; Advisory / Consultancy: Mass-Array; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche. C.U. Blank: Advisory / Consultancy: MSD; Advisory / Consultancy, Research grant / Funding (self): BMS; Advisory / Consultancy: Roche; Advisory / Consultancy: GSK; Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: GenMab; Advisory / Consultancy: Lilly; Research grant / Funding (self): NanoString; Advisory / Consultancy: Pierre Fabre. All other authors have declared no conflicts of interest.