Single-Dose Neoadjuvant Pembrolizumab in Resectable Metastatic Melanoma

Neoadjuvant immune checkpoint blockade therapy for resectable oligometastatic melanoma has shown promising results in clinical trials; however, investigation into the optimal agent and dosing schedule is ongoing. We report on the largest case series of patients with oligometastatic melanoma treated with a single dose of neoadjuvant programmed cell death receptor 1 (PD-1) inhibition.

We identified PD-1 naive patients with resectable stage III/IV melanoma who received one dose of pembrolizumab (200 mg intravenous) prior to surgical resection at a single high-volume melanoma center. Outcomes included time to surgery, 30-day surgical complications, time to initiation of adjuvant therapy, major pathologic response (MPR) defined as < 10% viable tumor, patterns/treatment of first recurrence, and 5-year recurrence-free and overall survival.

Of 51 patients, there were no grade 3/4 immune-related adverse events prior to surgery and no delays in surgery. The majority of patients (70.6%) had no postoperative complications, and none were Clavien-Dindo grade 3 or higher. There was prompt initiation of adjuvant therapy, along with appreciable rates of MPR (19.6%). In total, 45.1% of the cohort experienced a recurrence including two patients who had an MPR. For patients who achieved MPR, 5-year overall survival was 100%.

A single dose of neoadjuvant pembrolizumab is a safe and feasible approach with potential for early pathological readout of responsiveness to neoadjuvant therapy. Late recurrences were observed in the MPR group, indicating need for follow-up but were salvageable. Further biomarker work is needed to identify patients who would benefit from neoadjuvant single agent anti-PD-1 therapy.