Neoadjuvant Immune Therapy in Patients With Melanoma: Response and Toxicity in a Non-Clinical Trial Setting

Neoadjuvant therapy with immune checkpoint inhibitors (ICIs) is increasingly used in advanced or recurrent melanoma based on outcomes observed in clinical trials. The efficacy and toxicity of this in a real-world setting remain unclear.

We conducted a retrospective review of adults with cutaneous melanoma who received neoadjuvant ICI as first line therapy at our institution between 2019 and 2024. Patients had advanced melanoma that was surgically resectable and treated with neoadjuvant intent. The primary outcome was pathological response, with a secondary outcome of immune-related toxicity.

In total, 81 patients were identified. The median age was 64 (range: 21-86). There were 48 males. Most patients received 2 cycles (n = 53) prior to resection (range: 1-7 cycles). Dual ICI was the most common approach (n = 62). Disease stage ranged from IIC to IV, with 57% IIIC. Half were pathologic non-responders (n = 41). Pathologic complete response (pCR) was seen in 25% (n = 20), near-pCR in 2% (n = 2) and partial PR in 10% (n = 8). Ten (12%) patients had a discrepant PR between two or more resected sites. Immune related adverse events were observed in 34 (42%) patients; 21 (26%) grade 1-2, and 13 (16%) grade 3-4. Overall survival trended towards significance (p = 0.07) for those with mPR.

Non-trial use of neoadjuvant ICI therapy is associated with a less favourable pathological response than reported in clinical trials and similar risks of toxicity.