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Baseline circulating IL-17 predicts toxicity while TGF-β1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma

Tarhini, AA and Zahoor, H and Lin, Y and Malhotra, U and Sander, C and Butterfield, LH and Kirkwood, JM (2015) Baseline circulating IL-17 predicts toxicity while TGF-β1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma. Journal for ImmunoTherapy of Cancer, 3 (1).

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Abstract

© 2015 Tarhini et al. Background: We evaluated candidate circulating serum cytokines, chemokines and growth factors in patients with locally/regionally advanced melanoma receiving neoadjuvant ipilimumab with toxicity and clinical outcome. Methods: Patients were treated with ipilimumab (10mg/kg IV every 3weeks, 2 doses) before and after surgery. xMAP multiplex serum testing for 36 functionally selected cytokines and chemokines was performed at baseline and at six weeks (following ipilimumab). Based on our prior data, the association of IL-17 and immune related colitis was tested. Serum cytokines were divided into functional groups (Th1, Th2, Regulatory, Proinflammatory) and were assessed at baseline and week 6 using sparse-group Lasso modeling to assess the association of various cytokine groups with progression free survival (PFS). The linear combination of the cytokines/chemokines in this model was then used as a risk score and a Kaplan-Meier curve was generated to examine the association of the dichotomized score and PFS. Results: Thirty-five patients were enrolled whose staging was: IIIB (3; N2b), IIIC (30; N2c, N3), IV (2). Median follow-up was 18months. Among 33 evaluable patients, median PFS was 11months (95% CI=6.2-19.2). IL-17 was found to correlate significantly with the incidence of grade 3 diarrhea/colitis when measured at baseline (p=0.02) with a trend towards significance at 6weeks (p=0.06). In the modeling analysis, at baseline, the linear combination of 2 regulatory cytokines [TGF- β1 (p=0.19) and IL-10 (p=-0.34)] was significantly associated with PFS (HR 2.66; p=0.035). No significant correlations with clinical outcomes were found in examining the week 6 cytokines. Conclusions: Baseline IL-17 level was significantly associated with the later development of severe diarrhea/colitis while the combination of baseline TGF- β1 and IL-10 levels were associated with therapeutic clinical outcome after neoadjuvant ipilimumab. These findings warrant further investigation and validation. Trial registration: ClinicalTrials.gov Identifier NCT00972933.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Tarhini, AAaat8@pitt.eduAAT8
Zahoor, Hhaz42@pitt.eduHAZ42
Lin, Yyal14@pitt.eduYAL14
Malhotra, U
Sander, Ccas32@pitt.eduCAS32
Butterfield, LHlhb3@pitt.eduLHB3
Kirkwood, JMkirkwood@pitt.eduKIRKWOOD
Centers: Other Centers, Institutes, or Units > Pittsburgh Cancer Institute
Date: 15 September 2015
Date Type: Publication
Journal or Publication Title: Journal for ImmunoTherapy of Cancer
Volume: 3
Number: 1
DOI or Unique Handle: 10.1186/s40425-015-0081-1
Refereed: Yes
Date Deposited: 09 Aug 2016 17:06
Last Modified: 02 Feb 2019 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/29200

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