Background: Melanoma regional lymph node and in-transit metastases (stage IIIB-C) carry a high relapse and mortality risk. Neoadjuvant ipilimumab may modulate the host suppressor immune response, enhance antitumor immunity and improve the clinical outcome. Methods: Patients with clinically palpable stage IIIB-C melanoma were treated with induction ipilimumab (10 mg/kg IV q3weeks x2doses) preoperatively and had definitive lymphadenectomy (week ≥ 6), followed by 2 maintenance doses of ipilimumab (q3 weeks). Tissue samples were obtained at baseline and at definitive surgery (after 2 doses of ipilimumab) and blood (serum/PBMC) collected at baseline, 6 weeks, then at 3, 6, 9, 12 months and/or progression. Circulating T-regulatory cells (T-regs) and myeloid derived suppressor cells (MDSC) were monitored utilizing multicolor flow cytometry comparing preoperative (6 weeks) and baseline samples. Results: Twenty nine patients (20 male, 9 female), age 40-87 (median 54) have been enrolled since February/2010 (24 cutaneous primary, 1 unknown and 4 mucosal). Five had AJCC stage IIIB (N2b, N2c) and 24 had IIIC (N3) melanoma. Ninety one cycles have been delivered (median 4). Grade 3 (worst) toxicities include diarrhea/colitis (5 patients; 17%), hepatic enzyme elevations (2; 7%), rash (2; 7%), lipase (1; 3%), all manageable. Median follow-up is 9.7 months and 18 patients (62%) continue disease free. Median PFS is 15.5 months, 95% CI = (8.1, -). The probability of 6 and 12 months PFS is 84.2% (95% CI=0.63, 0.94) and 54.1% (95% CI=0.31, 0.73) respectively. There is a significant increase in the frequency of circulating T-regs (CD4+CD25hi+ Foxp3+; p=0.023 CD4+CD25hi+CD39+; p=0.001) from baseline to 6 weeks. In parallel there is a significant decrease in circulating MDSCs: (1) monocytic: HLA-DR+/low/CD14+; p=<.0001 and less significantly for (2) other monocytic: lin1neg/HLA-DRneg/CD33+/CD11b+; p=0.198 and (3) lymphoid: Lin1neg/HLA-DR-/CD33+/CD11b+; p=0.338. Conclusions: Neoadjuvant ipilimumab is clinically promising and significantly downregulates MDSCs which appear to play a significant role in the clinical activity of ipilimumab. T-regs are upregulated as part of the overall CD4+ T-cell population, and functional studies of this population are ongoing.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5375. doi:1538-7445.AM2012-5375