Combination of Ipilimumab and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma

Frontiers in Oncology

卷:8

Shari Pilon-Thomas¹  James J. Mulé¹  Amod A. Sarnaik¹  Joseph Markowitz¹  Allison Richards¹  Zeynep Eroglu¹  Valerie Stark¹  Vernon K. Sondak¹  Nikhil Khushalani¹  Andrew S. Brohl¹  Jonathan S. Zager¹  Erica Royster¹  Sangeetha Prabhakaran²  John E. Mullinax³  Cheryl Cox³  Linda Kelley³  MacLean Hall³  Jeffrey Weber⁴ 

[1] Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, United States;

[2] Department of Surgery, University of New Mexico, Albuquerque, NM, United States;

[3] Immunology Department, Moffitt Cancer Center, Tampa, FL, United States;

[4] NYU Langone Medical Center, New York, NY, United States;

[5] Sarcoma Department, Moffitt Cancer Center, Tampa, FL, United States;

关键词: adoptive cell therapy;    melanoma;    ipilimumab;    checkpoint inhibitor;    immunotherapy;    tumor-infiltrating lymphocytes;   

DOI  :  10.3389/fonc.2018.00044

来源: DOAJ

【 摘 要 】

PurposeAdoptive 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 designThirteen 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).ResultsAll patients received at least two doses of ipilimumab, and 12 of the 13 (92%) received TIL. A median of 6.5 × 1010 (2.3 × 1010 to 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).ConclusionIpilimumab 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.

【 授权许可】

Unknown