Title |
Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma
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Published in |
Frontiers in oncology, March 2018
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DOI | 10.3389/fonc.2018.00044 |
Pubmed ID | |
Authors |
John E. Mullinax, MacLean Hall, Sangeetha Prabhakaran, Jeffrey Weber, Nikhil Khushalani, Zeynep Eroglu, Andrew S. Brohl, Joseph Markowitz, Erica Royster, Allison Richards, Valerie Stark, Jonathan S. Zager, Linda Kelley, Cheryl Cox, Vernon K. Sondak, James J. Mulé, Shari Pilon-Thomas, Amod A. Sarnaik |
Abstract |
Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) for metastatic melanoma can be highly effective, but attrition due to progression before TIL administration (32% in prior institutional experience) remains a limitation. We hypothesized that combining ACT with cytotoxic T lymphocyte-associated antigen 4 blockade would decrease attrition and allow more patients to receive TIL. Thirteen patients with metastatic melanoma were enrolled. Patients received four doses of ipilimumab (3 mg/kg) beginning 2 weeks prior to tumor resection for TIL generation, then 1 week after resection, and 2 and 5 weeks after preconditioning chemotherapy and TIL infusion followed by interleukin-2. The primary endpoint was safety and feasibility. Secondary endpoints included of clinical response at 12 weeks and at 1 year after TIL transfer, progression free survival (PFS), and overall survival (OS). All patients received at least two doses of ipilimumab, and 12 of the 13 (92%) received TIL. A median of 6.5 × 1010(2.3 × 1010to 1.0 × 1011) TIL were infused. At 12 weeks following infusion, there were five patients who experienced objective response (38.5%), four of whom continued in objective response at 1 year and one of which became a complete response at 52 months. Median progression-free survival was 7.3 months (95% CI 6.1-29.9 months). Grade ≥ 3 immune-related adverse events included hypothyroidism (3), hepatitis (2), uveitis (1), and colitis (1). Ipilimumab plus ACT for metastatic melanoma is feasible, well tolerated, and associated with a low rate of attrition due to progression during cell expansion. This combination approach serves as a model for future efforts to improve the efficacy of ACT. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 50% |
Switzerland | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 91 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 13 | 14% |
Student > Ph. D. Student | 11 | 12% |
Student > Master | 11 | 12% |
Student > Doctoral Student | 9 | 10% |
Student > Bachelor | 8 | 9% |
Other | 15 | 16% |
Unknown | 24 | 26% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 20 | 22% |
Biochemistry, Genetics and Molecular Biology | 13 | 14% |
Immunology and Microbiology | 9 | 10% |
Agricultural and Biological Sciences | 6 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 4% |
Other | 9 | 10% |
Unknown | 30 | 33% |