Ultrasound-Guided Fine-Needle aspiration cytology (USFNAC) to detect melanoma cells in the sentinel node facilitates local administration of medication, here IL-21 (rIL21) in a novel neoadjuvant setting into the sentinel node of stage III Melanoma Patients

PURPOSE The clinical setting of stage IV melanoma is not optimal for testing the effects of immunotherapeutic interventions. In order to explore the therapeutic effect of recombinant interleukin 21 (rIL-21) in the earlier stages of disease, we tested local subcutaneous (sc) administration of rIL-21 in a clinical setting of early stage III malignant melanoma. EXPERIMENTAL DESIGN The pilot trial was planned to enroll 20 patients with stage III melanoma as identified by high-resolution ultrasonography and fine-needle aspiration cytology (FNAC). Patients would receive rIL-21 administered sc in the area of the primary lesion for 4 weeks in a thrice-weekly regimen prior to complete regional lymph node dissection. Subsequently, patients would receive rIL-21 administered sc systemically for 8 weeks as adjuvant therapy. RESULTS Only one patient was entered in the trial, as the sponsor withdrew the trial for company strategic reasons. The patient, a 45-year-old male, completed the 4 weeks of local neoadjuvant rIL-21 therapy and underwent complete regional lymph node dissection. A total of 28 lymph nodes were examined by extensive slicing and histological examination involving immune histochemical staining with Melan-A and HMB-45. No signs of micro- or macrometastatic disease were observed. CONCLUSION Although only one patient entered the trial, local and sc administration of rIL-21 was shown to have clear immunomodulatory effects in the tumor-draining lymph nodes and resulted in a complete response, as assessed by histological examination of the resected lymph nodes. This observation may have implications for future immunotherapeutic interventions in patients with melanoma.