Effect of clinical status and previous treatment of melanoma patients on expansion of TIL for adoptive T-cell therapy

Abstract

3021 Background: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) is a promising therapy for the treatment of metastatic melanoma. Trials at the NCI have shown a 50% response rate. However, outside of the NCI, ACT has been quite limited and little is known about how patient characteristics and prior treatment affect large-scale TIL expansion needed for treatment. Methods: As part of a phase II melanoma ACT clinical trial at M. D. Anderson Cancer Center, we evaluated how clinical characteristics such as age, gender, biopsy site, melanoma type, primary tumor location, and prior treatment of patients (N=134) affected TIL expansion rates. 159 isolated metastatic melanomas (19 patients having >1 tumor harvest) were analyzed for the ability to expand a minimum of 40 million TIL, considered a minimum number for the subsequent rapid expansion protocol (REP) needed for TIL infusion. Effects of these parameters on TIL anti-tumor reactivity and TIL/tumor fragment were also analyzed. Statistical analysis was done by either Fisher's Exact test, Wilcoxon Rank Sum test, or Kruskal-Wallis Test. Results: 54.7% of the samples evaluated generated ≥ 40 million TIL, and 70% of 70 samples tested had anti-tumor reactive TIL. There was a significant relationship between age categories (p=0.0216) and gender (p=0.0164) on TIL expansion success. Younger patients did the best and females did better than males (odds 2.19, p=0.044). The site of the primary melanoma affected success of TIL expansion (p=0.0059), while no effect of tumor biopsy site and histological type was found. Prior chemotherapy (or biochemotherapy) greatly reduced TIL growth (odds 0.32, p=0.010) when compared to no prior therapy. Multivariate linear regression analyses showed that prior chemotherapy decreased TIL/tumor fragment yield by 6.19 million (p=0.0004) while immunotherapy increased it by 3.51 million (p=0.16) compared to no prior therapy. Total TIL yield or TIL/tumor fragment did not correlate with patient overall survival. Conclusions: Parameters such as age, sex, primary melanoma site, and prior therapy significantly affect TIL expansion and should be considered in selecting patients for melanoma ACT. No significant financial relationships to disclose.