Extended Dose Ipilimumab with a Peptide Vaccine: Immune Correlates Associated with Clinical Benefit in Patients with Resected High-Risk Stage IIIc/IV Melanoma

• Published in: Clinical cancer research Vol. 17; no. 4; pp. 896 - 906
• Main Authors: SARNAIK, Amod A, BIN YU, YELLIN, Michael, WEBER, Jeffrey S, DAOHAI YU, DAWN MORELLI, HALL, Maclean, BOGLE, Dilip, LULU YAN, TARGAN, Stephan, SOLOMON, Jolie, NICHOL, Geoff
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.02.2011
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - adverse effects; Adult; Aged; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Biological and medical sciences; Cancer Vaccines - administration & dosage; Cancer Vaccines - adverse effects; Dermatology; Female; Humans; Ipilimumab; Kaplan-Meier Estimate; Male; Medical sciences; Melanoma - immunology; Melanoma - pathology; Melanoma - therapy; Middle Aged; Monocytes - drug effects; Monocytes - immunology; Neoplasm Recurrence, Local; Neoplasm Staging; Pharmacology. Drug treatments; Treatment Outcome; Tumors of the skin and soft tissue. Premalignant lesions; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - adverse effects; Young Adult; Human; High risk; Peptides; Ipilimumab; Patient; Surgical resection; Vaccine; Monoclonal antibody; Malignant tumor; Treatment; Surgery; Malignant melanoma; Advanced stage; Dose; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-10-2463

To determine safety and feasibility of adjuvant ipilimumab following resection of high-risk melanoma and to identify surrogate markers for benefit. In this phase II trial, 75 patients with resected stage IIIc/IV melanoma received the CTLA-4 antibody ipilimumab every 6 to 8 weeks for 1 year. Eligible patients received further maintenance treatments. The first 25 patients received 3 mg/kg of ipilimumab, and an additional 50 patients received 10 mg/kg. HLA-A*0201+ patients received multipeptide immunizations in combination with ipilimumab. Leukapheresis was performed prior to and 6 months after initiation of treatment. Median overall and relapse-free survivals were not reached after a median follow-up of 29.5 months. Significant immune-related adverse events were observed in 28 of 75 patients and were positively associated with longer relapse-free survival. Antigen-specific T cell responses to vaccine were variable, and vaccine combination was not associated with additional benefit. No effects on T regulatory cells were observed. Higher changes in Th-17 inducible frequency were a surrogate marker of freedom from relapse (P = 0.047), and higher baseline C-reactive protein (CRP) levels were associated with freedom from relapse (P = 0.035). Adjuvant ipilimumab following resection of melanoma at high risk for relapse appeared to be associated with improved outcome compared to historical reports. Significant immune-related adverse events were generally reversible and appeared to be associated with improved relapse-free survival. Although vaccination failed to induce a consistent in vitro measurable response, a higher change in Th-17 inducible cells and higher baseline CRP levels were positively associated with freedom from relapse.