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Autoimmunity Correlates With Tumor Regression in Patients With Metastatic Melanoma Treated With Anti–Cytotoxic T-Lymphocyte Antigen-4
Open accessAbstract
Purpose: Previously, we reported our experience treating 14 patients with metastatic melanoma using a fully human antibody to cytotoxic T-lymphocyte antigen-4 (anti–CTLA-4) in conjunction with peptide vaccination. We have now treated 56 patients to evaluate two different dose schedules of anti–CTLA-4 and to explore the relationship between autoimmunity and tumor regression. Patients and Methods: A total of 56 patients with progressive stage IV melanoma were enrolled onto the study. All had Karnofsky performance status ≥ 60% with no prior history of autoimmunity. Twenty-nine patients received 3 mg/kg anti–CTLA-4 every 3 weeks, whereas 27 received 3 mg/kg as their initial dose with subsequent doses reduced to 1 mg/kg every 3 weeks. In both cohorts patients received concomitant vaccination with two modified HLA-A*0201-restricted peptides from the gp100 melanoma-associated antigen, gp100:209-217(210M) and gp100:280-288(288V). Results: Two patients achieved a complete response (ongoing at 30 and 31 months, respectively) and five patients achieved a partial response (durations of 4, 6, 25+, 26+, and 34+ months, respectively), for an overall objective response rate of 13%. Tumor regression was seen in lung, liver, brain, lymph nodes, and subcutaneous sites. Of 14 patients with grade 3/4 autoimmune toxicity, five (36%) experienced a clinical response compared with only two responses in the 42 patients (5%) with no autoimmune toxicity (P = .008). There were no significant differences in response rate or toxicity between the two dose schedules. Conclusion: Administration of anti–CTLA-4 monoclonal antibody plus peptide vaccination can cause durable objective responses, which correlate with the induction of autoimmunity, in patients with metastatic melanoma.
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“patients who experienced grade 3/4 IRAEs had an improved ORR compared to those who did not experience grade 3/4 IRAEs (36% vs 5%, p = .008) [45].”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [45]
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Metadata
- Authors
- Attia, P., Phan, G. Q., Maker, A. V., Robinson, M. R., Quezado, M. M., Yang, J. C., Sherry, R. M., Topalian, S. L., Kammula, U. S., Royal, R. E., Restifo, N. P., Haworth, L. R., Levy, C., Mavroukakis, S. A., Nichol, G., Yellin, M. J., & Rosenberg, S. A.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2005-09-01
- Volume
- 23
- Issue
- 25
- Pages
- 6043-6053
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC1473965
- OpenAlex
- W2151507811
- Cited by
- 1,012
- References
- 44
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 18 · 2023: 17 · 2022: 31 · 2021: 45 · 2020: 81 · 2019: 46 · 2018: 45 · 2017: 55 · 2016: 60 · 2015: 64 · 2014: 49 · 2013: 63 · 2012: 43
- FWCI
- 30.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 CA999999)
- National Cancer Institute (Z01BC010763)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Keywords
- metastatic melanoma, anti-CTLA-4 monoclonal antibody, CTLA-4 blockade, autoimmunity, autoimmune toxicity, tumor regression, peptide vaccination, gp100, dosing regimen, immune checkpoint inhibitors, objective response rate
- MeSH terms
- Adult, Aged, Antigens, Differentiation, Drug Administration Schedule, Female, Humans, Immunosuppressive Agents, Injections, Intravenous, Male, Melanoma, Middle Aged, Prognosis, Skin Neoplasms, Autoimmunity, Antigens, CD, Treatment Outcome, Cancer Vaccines, CTLA-4 Antigen
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