Assessment of neuronal autoantibodies in patients with Small Cell Lung Cancer treated with chemotherapy with or without Ipilimumab
Assessment of neuronal autoantibodies in patients with Small Cell Lung Cancer treated with chemotherapy with or without Ipilimumab
Small-cell lung cancer (SCLC) is often associated with paraneoplastic syndromes. To assess the role of anti-neuronal autoantibodies (NAAs) as biomarkers of treatment outcome, we assessed NAAs in serial samples from SCLC patients treated with chemoimmunotherapy compared to chemotherapy alone. We evaluated 2 cohorts: in cohort 1 (C1), 47 patients received standard platinum/etoposide, and in cohort 2 (C2), 38 patients received ipilimumab, carboplatin and etoposide. Serum samples at baseline and subsequent time points were analyzed for the presence of NAAs. NAAs were detected at baseline in 25 patients (53.2%) in C1 and in 20 patients (52.6%) in C2 (most frequently anti-Sox1). NAA at baseline was associated with limited disease (75% vs 50%; p: 0.096) and better overall survival (15.1m vs 11.7m; p: 0.032) in C1. Thirteen patients (28.9%) showed 2or more reactivities before treatment; this was associated with worse PFS (5.5m vs 7.3m; p: 0.005) in patients treated with chemoimmunotherapy. NAA titers decreased after therapy in 68.9% patients, with no differential patterns of change between cohorts. Patients whose NAA titer decreased after treatment, showed longer OS [18.5m (95% CI: 15.8 – 21.2)] compared with those whose NAA increased [12.3m (95% CI: 8.1 – 16.5; p 0.049)], suggesting that antibody levels correlate to tumor load. Our findings reinforce the role of NAAs as prognostic markers and tumor activity/burden in SCLC, warrant further investigation in their predictive role for immunotherapy and raise concern over the use of immunotherapy in patients with more than one anti-NAA reactivity.
Hardy-Werbin, M.
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Arpi, O.
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Taus, A.
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Rocha, P.
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Joseph-Pietras, D.
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Nolan, L.
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Danson, S.
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Griffiths, R.
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Lopez-Botet, M.
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Rovira, A.
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Albanell, J.
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Ottensmeier, C.
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Arriola, E.
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Hardy-Werbin, M.
ebbd102f-c7fa-4457-b20d-966e44daa8fc
Arpi, O.
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Taus, A.
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Rocha, P.
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Joseph-Pietras, D.
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Nolan, L.
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Danson, S.
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Griffiths, R.
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Lopez-Botet, M.
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Rovira, A.
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Albanell, J.
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Ottensmeier, C.
42b8a398-baac-4843-a3d6-056225675797
Arriola, E.
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Hardy-Werbin, M., Arpi, O., Taus, A., Rocha, P., Joseph-Pietras, D., Nolan, L., Danson, S., Griffiths, R., Lopez-Botet, M., Rovira, A., Albanell, J., Ottensmeier, C. and Arriola, E.
(2017)
Assessment of neuronal autoantibodies in patients with Small Cell Lung Cancer treated with chemotherapy with or without Ipilimumab.
OncoImmunology, 7 (2), [e1395125].
(doi:10.1080/2162402X.2017.1395125).
Abstract
Small-cell lung cancer (SCLC) is often associated with paraneoplastic syndromes. To assess the role of anti-neuronal autoantibodies (NAAs) as biomarkers of treatment outcome, we assessed NAAs in serial samples from SCLC patients treated with chemoimmunotherapy compared to chemotherapy alone. We evaluated 2 cohorts: in cohort 1 (C1), 47 patients received standard platinum/etoposide, and in cohort 2 (C2), 38 patients received ipilimumab, carboplatin and etoposide. Serum samples at baseline and subsequent time points were analyzed for the presence of NAAs. NAAs were detected at baseline in 25 patients (53.2%) in C1 and in 20 patients (52.6%) in C2 (most frequently anti-Sox1). NAA at baseline was associated with limited disease (75% vs 50%; p: 0.096) and better overall survival (15.1m vs 11.7m; p: 0.032) in C1. Thirteen patients (28.9%) showed 2or more reactivities before treatment; this was associated with worse PFS (5.5m vs 7.3m; p: 0.005) in patients treated with chemoimmunotherapy. NAA titers decreased after therapy in 68.9% patients, with no differential patterns of change between cohorts. Patients whose NAA titer decreased after treatment, showed longer OS [18.5m (95% CI: 15.8 – 21.2)] compared with those whose NAA increased [12.3m (95% CI: 8.1 – 16.5; p 0.049)], suggesting that antibody levels correlate to tumor load. Our findings reinforce the role of NAAs as prognostic markers and tumor activity/burden in SCLC, warrant further investigation in their predictive role for immunotherapy and raise concern over the use of immunotherapy in patients with more than one anti-NAA reactivity.
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Manuscript Hardy-Werbin et al (with figures)
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Accepted/In Press date: 17 October 2017
e-pub ahead of print date: 27 November 2017
Identifiers
Local EPrints ID: 415462
URI: http://eprints.soton.ac.uk/id/eprint/415462
ISSN: 2162-402X
PURE UUID: 8bd72b28-11b0-44d9-9540-d2065493a0c0
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Date deposited: 10 Nov 2017 17:30
Last modified: 16 Mar 2024 05:54
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Contributors
Author:
M. Hardy-Werbin
Author:
O. Arpi
Author:
A. Taus
Author:
P. Rocha
Author:
D. Joseph-Pietras
Author:
L. Nolan
Author:
S. Danson
Author:
R. Griffiths
Author:
M. Lopez-Botet
Author:
A. Rovira
Author:
J. Albanell
Author:
E. Arriola
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