Real world outcomes of neoadjuvant immune checkpoint blockade (ICB) for resectable stage III melanoma: Pathologic response and FDG PET/CT correlates.

Abstract

9569 Background: Neoadjuvant (NA) ICB is standard of care for resectable stage III melanoma, with major pathological (p) response (R) (MPR, ≤10% viable tumor) strongly predicting relapse free survival (RFS). Imaging biomarkers to predict MPR are lacking. We evaluated the outcomes of patients (pts) treated with NA pembrolizumab (Pem) or nivolumab (NIVO) + ipilimumab (IPI) therapy, focusing on pR and FDG PET/CT metabolic changes. Methods: We retrospectively analyzed pts with resectable stage IIIB-D melanoma treated with NA Pem or NIVO + IPI at Peter Mac from March 2022 to Dec 2025. Clinical characteristics, pR, RFS, and treatment-related adverse events (TRAEs) were analyzed. RFS was calculated from date of surgery until day of death, recurrence or last follow up. Maximum standardized uptake value (SUVmax) of the most avid lesion (lymph node (LN) or in-transit metastases (ITM)) at baseline and post NA ICB on FDG PET/CT scans were recorded. Results: Of the 130 pts, 100 had LN metastasis only, 19 ITM only and 11 LN + ITM. 77 (59.2%) received Pem and 53 (40.8%) received NIVO + IPI. 117 pts (90.0%) underwent surgery: LN dissection in 40, index LN (ILN) excision in 58, ITM excision in 18 and excision of ITM + ILN in 1. 13 pts did not have surgery, 10 due to progressive disease on FDG PET/CT, complete resolution of ITM in 2, and toxicity in 1. MPR was seen in 74 (63.2%), partial response (pPR) in 7 (6.0%) and pathological non-response (pNR) in 36 (30.8%) pts. A ∆SUVmax decline ≥50% post NA ICB was strongly predictive of MPR, whereas pts without significant metabolic response were more likely to have pNR (sensitivity 93.2%, specificity 60.0%, positive predictive value 71.9%, negative predictive value 88.9% and accuracy 77.4% p =0.005). In ILN disease, 40/43 pts (93.0%) with ≥50% drop in ∆SUVmax achieved MPR (p<0.0001). In ITMs, a decline in ∆SUVmax ≥50% resulted in MPR in all 10 pts (table 1). At 12 months (m) median follow up, 14 pts recurred including 4 after MPR. The estimated 12m RFS was 89.0% for Pem and 79.3% for NIVO + IPI. 12m RFS in pts with ∆SUVmax decline ≥50% for Pem was 97% and 82% for NIVO + IPI ( p =0.045). Grade ≥3 TRAEs occurred in 12 pts (7.5%), more frequently with NIVO + IPI. Conclusions: NA ICB yields high MPR rates in stage III melanoma. Early metabolic response on FDG PET/CT, defined as a ΔSUVmax ≥50% decline is a strong, readily implementable imaging biomarker for predicting MPR following NA ICB, enabling early treatment adaptation and personalized surgical decision-making. Pem (n=77) NIVO + IPI (n=53) Median age [range] 67 [41-92] 67 [20-82] BRAF mutant, n (%) 23 (29.9) 27 (50.9) Stage III B/C/D, n 26/50/1 20/33/0 Site of disease, neck/axilla/groin/ITM, n 23/28/13/13 18/20/12/6 MPR, n (%) 45 (65.2) 29 (60.4) MPR ∆SUVmax decline ≥50% 33/35 13/14 MPR ∆SUVmax decline <50% 12/34 7/22 12m RFS ∆SUVmax decline ≥50% (95% CI) 96% (89%-100%) 100% 12m RFS ∆SUVmax decline <50% (95% CI) 82% (67%-100%) 80% (59%-100%)