Abstract 1357: Serum levels of programmed cell death molecule-1 (PD-1) as a biomarker in metastatic melanoma patients randomized for treatment with autologous dendritic cell or tumor cell vaccines
Authors: Dillman Robert O. , Nistor Gabriel I. , Poole Aleksandra J. , Cornforth Andrew N. 
Published: August 2019

Abstract
The purpose of this study was to analyze PD-1 serum levels, in patients with metastatic melanoma who were enrolled in a randomized phase 2 trial, to determine: [1] if baseline PD-1 serum levels were prognostic for overall survival (OS), [2] if baseline PD-1 levels were predictive for survival benefit in the specific treatment arms, [3] if PD-1 levels changed between week-0 and week-4 by treatment, and [4] if changes in PD-1 levels were predictive of survival benefit overall and by treatment. Patients with metastatic melanoma were enrolled in a randomized phase 2 clinical trial comparing treatment with autologous dendritic cell vaccines (DCV) presenting autologous tumor antigens (ATA) derived from irradiated cancer cells from short-term autologous cell lines, compared to tumor cell vaccines (TCV) consisting of irradiated tumor cells [Dillman et al. J ImmunoTher Cancer 2018]. Vaccines were injected s.c. weekly for three weeks, then at weeks 8, 12, 16, 20, and 24. OS was longer for patients treated with DCV (median 43 vs 20 months; 70% reduction in risk of death). Cryopreserved serum samples from week-0 and week-4 for 39/42 patients were analyzed using a quantitative, multiplex enzyme-linked immunosorbent assay (Raybiotech, Inc., Norcross, GA). The patients for whom PD-1 levels were missing were two TCV-treated subjects who had rapidly progressive disease and had no week-4 samples, and one DCV-treated subject who survived more than 5-years, but rescinded permission to test his blood. Baseline serum PD-1 levels ranged from 0 to 511 ng/ml. After three weekly vaccinations, median serum levels of PD-1 did not change between week-0 and week-4 (1.51 and 1.58 ng/ml), nor did mean serum levels change (52.5 and 52.6 ng/ml). For all 39 patients, baseline PD1 levels were not prognostic for OS. DCV was associated with longer OS than TCV both in patients whose baseline PD1 was &lt;1.2 ng/ml and &gt; 1.2 ng/ml. Among DCV-treated subjects, baseline levels &lt;50 ng/ml were associated with OS &gt; 3.5 years in 9/13 compared to 0/4 for those with levels &gt; 50 ng/ml (p=0.029), but there was no difference in the TCV arm (5/19 vs 1/3, p=1.00). Overall, PD1 levels decreased after 3 DCV injections, but increased after 3 TCV injections. DCV-treated subjects who had a decrease in PD-1 were more likely to survive 4 years (6/9 vs 1/8, p=0.05) but this difference was not seen in patients treated with TCV (0/6 vs 6/16, p=0.289). CONCLUSONS: In these metastatic melanoma patients, baseline serum PD1 levels were not prognostic for survival, but were predictive of survival benefit in patients treated with DCV, as was a decrease in PD1 level after 3 weekly DCV vaccinations. PD1 levels should be prospectively evaluated in larger studies to see if they may be useful as a companion diagnostic and/or surrogate marker for efficacy.
Citation Format: Robert O. Dillman, Gabriel I. Nistor, Aleksandra J. Poole, Andrew N. Cornforth. Serum levels of programmed cell death molecule-1 (PD-1) as a biomarker in metastatic melanoma patients randomized for treatment with autologous dendritic cell or tumor cell vaccines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1357.