Evaluation of Ipilimumab in Combination With Allogeneic Pancreatic Tumor Cells Transfected With a GM-CSF Gene in Previously Treated Pancreatic Cancer
| Autor: | Elizabeth A. Sugar, Daniel A. Laheru, Sara Solt, Dung T. Le, Jennifer N. Uram, Ross C. Donehower, Beth Onners, Luis A. Diaz, Lei Zheng, Elizabeth M. Jaffee, Eric R. Lutz |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Cancer Research T-Lymphocytes Immunology Antineoplastic Agents Ipilimumab GPI-Linked Proteins Transfection Cancer Vaccines Article Pancreatic tumor Pancreatic cancer medicine Humans Immunology and Allergy Cytotoxic T cell CTLA-4 Antigen Aged Pharmacology business.industry Granulocyte-Macrophage Colony-Stimulating Factor Antibodies Monoclonal Cancer Middle Aged medicine.disease Combined Modality Therapy GVAX Immune checkpoint Radiography Pancreatic Neoplasms CTLA-4 Mesothelin Female business Carcinoma Pancreatic Ductal medicine.drug |
| Zdroj: | Journal of Immunotherapy. 36:382-389 |
| ISSN: | 1524-9557 |
| Popis: | Preclinical reports support the concept of synergy between cancer vaccines and immune checkpoint blockade in nonimmunogenic tumors. In particular, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibodies have been successfully combined with GM-CSF cell-based vaccines (GVAX). Ipilimumab (anti-CTLA-4) has been tested as a single agent in patients with pancreatic ductal adenocarcinoma (PDA) resulting in a delayed response at a dose of 3 mg/kg. Our study evaluated ipilimumab 10 mg/kg (arm 1) and ipilimumab 10 mg/kg + GVAX (arm 2). A total of 30 patients with previously treated advanced PDA were randomized (1:1). Induction doses were administered every 3 weeks for a total of 4 doses followed by maintenance dosing every 12 weeks. Two patients in arm 1 showed evidence of stable disease (7 and 22 wk) but none demonstrated CA19-9 biochemical responses. In contrast, 3 patients in arm 2 had evidence of prolonged disease stabilization (31, 71, and 81 wk) and 7 patients experienced CA19-9 declines. In 2 of these patients, disease stabilization occurred after an initial period of progression. The median overall survival (OS) (3.6 vs. 5.7 mo, hazards ratio: 0.51, P = 0.072) and 1 year OS (7 vs. 27%) favored arm 2. Similar to prior ipilimumab studies, 20% of patients in each arm had grade 3/4 immune-related adverse events. Among patients with OS4.3 months, there was an increase in the peak mesothelin-specific T cells (P = 0.014) and enhancement of the T-cell repertoire (P = 0.031). In conclusion, checkpoint blockade in combination with GVAX has the potential for clinical benefit and should be evaluated in a larger study. |
| Databáze: | OpenAIRE |
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