Neoadjuvant immunotherapy in clinical stage III melanoma: Real life experience in the community setting.

Abstract

e21556 Background: There is a paradigm shift in the management of clinical stages IIIB-IIID melanoma. Results from phase II clinical trials revealed higher pathologic response rates in the neoadjuvant versus adjuvant setting. Methods: We conducted a retrospective study of patients with clinical stages IIIB-IIID melanoma who were deemed suitable for surgical resection and treated with neoadjuvant immunotherapy between January 2019 and December 2023. Patients must have had at least one cycle of neoadjuvant immunotherapy with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). The primary objective was to assess pathologic and radiologic response rates and to determine the association of pathologic response with event free survival (EFS). Results: Thirty-one patients were enrolled with a median age of 60 (range: 31-84) years. 61% of patients received two cycles, 3 weeks apart, of intravenous (IV) ipilimumab 1mg/kg and nivolumab 3mg/kg, while 23% received one cycle of IV ipilimumab 1mg/kg and nivolumab 3mg/kg followed by two cycles, 2 weeks apart, of IV nivolumab 240 mg. Twenty-nine patients underwent therapeutic lymph node dissection; of those 66% had a pathologic complete response (pCR) and 79% had an overall pathologic response. Complete radiologic response using RECIST 1.1 was detected in 28% and radiologic partial response in 56%. Next gene sequencing revealed a total of 47 mutations with BRAF V600 mutation being the most frequently encountered (28%) followed by mutations in TERT promoter (21%) and CDKN2A loss (13%). Two patients died during follow up. One patient refused surgery after neoadjuvant immunotherapy and passed away 4 years later due to stage IV melanoma. The second patient died two years after his surgery due to brain metastases despite achieving a complete pathologic response to neoadjuvant immunotherapy. Any grade adverse events (AE) were detected in 76% of patients; 64% grades 1-2 and 12% grades 3-4. Colitis was the most encountered grade 3 and 4 AE. Three-year event-free survival among 23 evaluable patients who had at least 6 months of follow up after surgery was 95%. Conclusions: Neoadjuvant immunotherapy with ipilimumab and nivolumab resulted in a high pathologic response rate of 79%. A discrepancy was detected between pathologic and radiologic responses. Colitis was the most common grade 3 and 4 toxicity. Three-year event free survival was 95%. Two patients died due to development of stage IV melanoma.