Abstract 100P
Background
PD-1 immune checkpoint inhibitor (ICI) therapy only induces clinical responses in a subgroup of metastatic melanoma (MM) patients. Response is associated with an increased population of M1-like macrophages that enhance T-cell responses. The stroma-derived serum biomarker VICM (citrullinated and matrix metalloproteinase-degraded vimentin) is released from activated M1 macrophages. We evaluated whether changes in VICM were associated with response to anti-PD-1 therapy in MM patients.
Methods
The cohort included MM patients (n=107) who started anti-PD-1 monotherapy between May 2016 – March 2019 by entering in a prospective observational study (nivolumab n=62, pembrolizumab n=45). Serum VICM levels were measured with ELISA at baseline and after six weeks of treatment, and the levels were compared with Wilcoxon paired t-test. Changes in VICM levels were correlated to median time-to-progression (TTP) and overall survival (OS) by Cox regression analyses after stratification of patients based on relative changes of >120% vs. <120% from baseline.
Results
Overall, VICM were significantly elevated after six weeks of anti-PD-1 therapy compared to baseline (median 21.4 vs 15.0 ng/ml; p<0.0001). Changes in VICM predicted for outcome: Patients with >120% increase in VICM had median TTP of 28.4 months vs. 8.4 months in patients with <120% increase in VICM (HR=0.59, 95%CI=0.35-1.01, p=0.056). These patients had also significantly better OS (HR=0.39, 95%CI=0.19-0.86, p=0.018) and VICM remained significant when adjusted for WHO performance status, brain metastases and lactate dehydrogenase (HR=0.28, 95%CI=0.10-0.77, p=0.014).
Conclusions
Increased levels following ICI therapy of the serum biomarker VICM that is released from activated M1 macrophages are associated with improved TTP and OS for MM patients treated with anti-PD-1 therapy. Altogether, this suggests that VICM may be used for monitoring early response to anti-PD-1 therapy. This study further highlights the importance of assessing stromal components and macrophage activity non-invasively in ICI studies.
Clinical trial identification
NTR7015.
Editorial acknowledgement
Legal entity responsible for the study
Nordic Bioscience.
Funding
The Danish Research Foundation and Erasmus Medical Center.
Disclosure
C. Jensen: Full/Part-time employment: Nordic Bioscience. S.L. Koolen: Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Cristal Therapeutics; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Pfizer. M.A. Karsdal: Shareholder/Stockholder/Stock options, Full/Part-time employment: Nordic Bioscience. R.H. Mathijssen: Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Boehringer-Ingelheim; Research grant/Funding (institution): Cristal Therapeutics; Research grant/Funding (institution): Pamgene; Research grant/Funding (institution): Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche; Advisory/Consultancy, Research grant/Funding (institution): Servier. N. Willumsen: Full/Part-time employment: Nordic Bioscience. All other authors have declared no conflicts of interest.