Circulating tumor DNA dynamics and pathologic response to neoadjuvant immunotherapy in resectable stage III melanoma.

e21560 Background: Pathologic response to neoadjuvant immunotherapy (NAI) can help predict recurrence in resectable stage III cutaneous melanoma. We investigated change in pre-surgery circulating tumor DNA (ctDNA) and its correlation with pathologic response and recurrence. Methods: We prospectively collected ctDNA at baseline, post-NAI (every 4-6 weeks), post-surgery in 21 resectable stage III melanoma patients who received NAI using Signatera at Inova Schar Cancer Institute. Following NAI, 6/21 (29%) achieved complete or near complete pathologic response (pCR/pnCR), 5/21 (24%) partial response (pPR), 10/21 (48%) non-response (pNR). At median follow up of 9 months, 3/10 (30%) patients with pNR recurred with a median time to recurrence of 11 months. None of pCR/pnCR/pPR recurred. Results: Baseline ctDNA was detectable in 14/21 (67%); 7 pNR, 7 non-pNR. Lack of post-NAI ctDNA clearance was observed in 6/7 (86%) pNR, while ctDNA clearance is observed in 7/7 (100%) non-pNR. Among pNR, post-NAI ctDNA decreased but never became 0 before surgery in 4/7 (57%) with one recurrence; increased without subsequent decrease in 2/7 (29%); not available in 1/7 (14%). Among non-pNR, post-NAI ctDNA was 0 in 3/7 (43%); increased with subsequent decrease in 3/7 (43%); increased without subsequent decrease in 1/7 (14%). Baseline ctDNA was 0 in 7/21 (33%). ctDNA remained 0 post-NAI and post-surgery in all of them with 2pCR/pnCR, 2pPR, 3pNR. Conclusions: Among patients with detected baseline ctDNA, lack of post-NAI ctDNA clearance prior to surgery may predict pNR. Larger study is needed to confirm this finding. Circulating tumor DNA dynamics and pathologic response. Baseline Post-NAI pCR/pnCR pPR pNR Total ctDNA detected ctDNA became 0 3 0 0 3 ctDNA increase then decrease 1 2 0 3 ctDNA increase without subsequent decrease 0 1 2 3 ctDNA decrease but not 0 0 0 4 (1 recurrence) 4 ctDNA not available 0 0 1(1 recurrence) 1 ctDNA not detected ctDNA remains 0 2 2 3 (1 recurrence) 7