Journal
FRONTIERS IN ONCOLOGY
Volume 8, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2018.00044
Keywords
adoptive cell therapy; melanoma; ipilimumab; checkpoint inhibitor; immunotherapy; tumor-infiltrating lymphocytes
Categories
Funding
- Swim Across America
- Iovance Biotechnologies
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Melanoma Research Alliance Team Science grant
- Melanoma SPORE grant [P50CA168536]
- Prometheus Laboratories Inc.
- Bristol-Myers-Squibb
- American Cancer Society--Leo and Anne Albert Charitable Foundation Research Scholar Grant [RSG-16-117-01-LIB]
- [NCI-5K23CA178083]
- [R01CA184845]
- NATIONAL CANCER INSTITUTE [K23CA178083] Funding Source: NIH RePORTER
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Purpose: 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. Experimental design: 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). Results: All patients received at least two doses of ipilimumab, and 12 of the 13 (92%) received TIL. A median of 6.5 x 10(10) (2.3 x 10(10) to 1.0 x 10(11)) 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). Conclusion: 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.
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