Previous studies have shown that reaching a pathologic complete response (pCR) using neoadjuvant therapy in patients with clinical stage III melanoma has correlated with improved relapse-free survival (RFS) and overall survival (OS). Balancing a favorable pCR with rates of toxicity has been a challenge with these therapies. Neoadjuvant therapy with high- or low-dose ipilimumab plus nivolumab (NIVO) has led to a pCR of 30% to 40%; however, the grade 3/4 toxicity rate for this combination is 20% to 90%. Based on data and experience with treating metastatic melanoma with NIVO plus relatlimab (RELA), which demonstrated low toxicity rates and high response rates in checkpoint inhibitor-naïve and refractory metastatic melanoma, the investigators hypothesized that neoadjuvant NIVO plus RELA would produce high pCRs with acceptable toxicity in patients with stage III melanoma.1
Patients (N = 30) with either measurable resectable clinical stage III or oligometastatic stage IV melanoma were administered NIVO 480 mg intravenously (IV) plus RELA 160 mg IV on weeks 1 and 5. After completion of neoadjuvant NIVO plus RELA, radiographic response was assessed. The patients then underwent surgery and resected specimens were assessed for pathologic response. Following surgery, they were administered up to 10 doses of NIVO plus RELA; scans were performed every 3 months to monitor for recurrence. The primary objective was the pCR rate. Secondary objectives were safety, radiographic response, event-free survival (EFS), RFS, and OS.1
Patients treated with NIVO plus RELA demonstrated a pCR rate of 59%; near pCR (<10% viable tumor) was 7% for a major pathologic response (MPR). A partial pathologic response (10%-50% viable tumor) was reached in 7% of patients and pathologic near response (≥50% viable tumor) was reached in 27%. The objective response rate was 57%. The 1-year EFS was 90%; the RFS was 93%; and the OS was 95% with a median follow-up of 16.2 months. In addition, the 1-year RFS for MPR was 100% and 80% for non-MPR. Grade 3/4 treatment-related adverse events occurred in 26% of patients during adjuvant therapy, but none occurred during neoadjuvant treatment.1
The researchers concluded that high pCR and MPR were achieved with neoadjuvant and adjuvant therapy with NIVO plus RELA with a favorable toxicity profile in both the neoadjuvant and adjuvant periods. In addition, patients with an MPR had better outcomes compared with patients with non-MPRs.1
- Amaria RN, Postow M, Tetzlaff MT, et al. Neoadjuvant and adjuvant nivolumab (nivo) with anti-LAG3 antibody relatlimab (rela) for patients (pts) with resectable clinical stage III melanoma. J Clin Oncol. 2021;39(suppl_15):9502-9502.