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Poster Display session 3

2286 - Extracellular matrix and tissue derived metabolites in a liquid biopsy identifies endotypes of metastatic melanoma patients with differential response to immune checkpoint inhibitor treatment

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Immunotherapy

Tumour Site

Melanoma

Presenters

Nicholas Willumsen

Citation

Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093/annonc/mdz253

Authors

N. Willumsen1, C.L. Bager1, C. Jensen1, M.A. Karsdal1, D.H. Madsen2, M. Hansen2, H. Schmidt3, I.M. Svane2

Author affiliations

  • 1 Biomarkers And Research, Nordic Bioscience A/S, 2730 - Herlev/DK
  • 2 Center For Cancer Immune Therapy, Department Of Haematology And Department Of Oncology, Herlev Hospital, University of Copenhagen, 2730 - Herlev/DK
  • 3 Department Of Oncology, Aarhus University Hospital, 8000 - Aarhus C/DK

Resources

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Abstract 2286

Background

The extracellular matrix (ECM) is a major component of tumors. Several recent findings link ECM composition with outcome in cancer patients treated with immune checkpoint inhibitors (ICIs). The aim here was to explore circulating ECM- and tissue-derived metabolites to enable clustering of patients with metastatic melanoma (MM) into putative endotypes and evaluate patient characteristics and outcome when treated with Ipilimumab accordingly.

Methods

Serum was collected from MM patients prior to treatment with Ipilimumab (n = 64). Wards hierarchical clustering of patients was based on 15 ECM- and tissue-derived metabolites measured in serum by ELISA. Identified clusters (endotypes) were compared to clinical characteristics and evaluated for associations with disease control rate (DCR), progression free survival (PFS) and overall survival (OS).

Results

Three putative endotypes (cluster A, B, C) were identified including 14, 30 and 20 patients, respectively. Overall a stepwise increase in ECM metabolite median levels were detected from C-B-A with the largest absolute change seen from B-A. There was no difference between A, B, and C according to age, gender, lactate dehydrogenase levels, number of metastasized organs and whether patients were treated previously. At follow-up, the DCR was 0%, 60% and 45% in A, B, and C, respectively. Likewise, patients with endotype A had a median PFS/OS time of 69/85 days versus 174/520 and 165/589 days for endotype B and C. In support, endotype A predicted for poor survival outcomes (PFSAvsB+C:HR=3.9, 95%CI:2.0-7.6, p = 0.0001; OSAvsB+C:HR:2.5, 95%CI:1.2-4.9, p = 0.0108).

Conclusions

Hierarchical clustering of MM patients based on 15 ECM- and tissue-derived metabolites measured in a liquid biopsy identifies 3 putative endotypes. One endotype (A) seems to reflect patients with an overall high and differentiated ECM turnover profile. These patients experience poor outcome when treated with Ipilimumab. If validated, this supports a link between ECM remodeling and outcome in cancer patients treated with ICIs.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Nordic Bioscience.

Funding

Has not received any funding.

Disclosure

N. Willumsen: Full / Part-time employment: Nordic Bioscience. C.L. Bager: Full / Part-time employment: Nordic Bioscience. C. Jensen: Full / Part-time employment: Nordic Bioscience. M.A. Karsdal: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Nordic Bioscience. H. Schmidt: Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Incyte; Advisory / Consultancy: Novartis; Research grant / Funding (institution): MSD; Travel / Accommodation / Expenses: Roche. I.M. Svane: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy: Pierre Faber; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self): Roche-Genentech; Travel / Accommodation / Expenses: Pfizer. All other authors have declared no conflicts of interest.

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