Assessment of neuronal autoantibodies in patients with small cell lung cancer treated with chemotherapy with or without ipilimumab

Hardy-Werbin, Max; Arpí, Oriol; Taus, Álvaro; Rocha, Pedro; Joseph-Pietras, Débora; Nolan, Luke; Danson, Sarah; Griffiths, Richard W.; López‐Botet, Miguel; Rovira, Ana; Albanell, Joan; Ottensmeier, Christian; Arriola, Edurne

doi:10.1080/2162402x.2017.1395125

Cited by 28 publications

(29 citation statements)

References 67 publications

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“…We retrospectively evaluated two independent cohorts of SCLC patients whose outcomes we have previously reported. 43 Patients from cohort 1 were recruited between November of 2009 and January of 2014 at the Hospital del Mar, Barcelona and treated with platinum plus etoposide. 44,45 Cohort 2 included patients recruited to a phase II trial of ipilimumab at 10mg/kg, platinum and etoposide (ICE-trial).…”

Section: Patients and Study Designmentioning

confidence: 99%

Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer

et al. 2019

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Background. Immunotherapy has shown efficacy in small cell lung cancer (SCLC), but only a subset of patients benefits. Surrogate biomarkers are urgently needed. Our aim was to evaluate serum Th1, Th2, and proinflammatory cytokines in two cohorts of SCLC patients before and during treatment with chemotherapy with or without ipilimumab and to correlate them with survival. Patients and methods. Two cohorts of SCLC patients were studied: patients treated with chemotherapy (n = 47), and patients treated with chemotherapy plus ipilimumab (n = 37). Baseline, on-treatment and after-treatment serum samples were evaluated for the presence of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, GM-CSF, and Mip-1alpha using a Luminex assay. Differential changes in cytokines between cohorts were analyzed. Associations between cytokine levels and their changes with overall survival were evaluated. Results. Patients treated with ipilimumab showed a global increase of all cytokines after treatment initiation. A high level of IL-8 at baseline was associated with worse prognosis regardless of treatment. Baseline increased IL-2 levels predicted sensitivity to ipilimumab, while high IL-6 and TNF-alpha predicted resistance. An on-treatment increase in IL-4 levels in patients treated with immune-chemotherapy was associated with a better overall survival.Conclusions. The addition of ipilimumab to standard chemotherapy in SCLC modulates the serum levels of cytokines. Baseline levels and their change over time relate to overall survival. Blood-based biomarkers are convenient for patients, and our results support prospective validation of cytokines as predictive biomarkers for ipilimumab in SCLC. ARTICLE HISTORY

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Section: Patients and Study Designmentioning

confidence: 99%

Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer

et al. 2019

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“…This meta-analysis suggests that chemotherapy combined with ipilimumab immunotherapy may improve the 6-month PFS/irPFS and the 1-year PFS compared with chemotherapy alone in patients with advanced or recurrent NSCLC and ED-SCLC. This improvement should be closely connected with the effect of ipilimumab's, and many studies have reported similar results 40 , 41 . Arriola E et al suggested that the median PFS was 6.9 months (95% CI: 5.5 7.9), that the median irPFS was 7.3 months (95% CI: 5.5 8.8) and that the median OS was 17.0 months (95% CI: 7.9 24.3) in patients with ED-SCLC after they were treated with ipilimumab immunotherapy.…”

Section: Discussionmentioning

confidence: 53%

Efficacy and Safety of Ipilimumab plus Chemotherapy for Advanced Lung Cancer: A Systematic Review and Meta-Analysis

Zhang

Shen

et al. 2018

J. Cancer

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Lung cancer is the leading cause of cancer-related deaths worldwide, with poor prognosis in advanced lung cancer patients. Platinum-based chemotherapy has always been a first-line treatment for the majority of advanced lung cancer patients, but its long-term survival benefit is limited. Ipilimumab is an immune drug that targets the CTLA-4 protein in T cells. Therefore, we evaluated the efficacy and safety of adding ipilimumab to simple chemotherapy for patients with advanced lung cancer. We searched literatures in PubMed, Web of Science, EMBASE, the Cochrane Library and cliniclatrials.gov. The primary end points of this assessment were overall survival (OS), progression-free survival (PFS) and immune-related PFS(irPFS) of lung cancer patients. Other end points were objective response rate (ORR), disease control rate (DCR) and safety. The results of this study will be presented by the risk ratio (RR) of the endpoints and the 95% confidence interval (CI) of the various effect sizes. And when the p value is less than 0.05, we think there is a statistical difference. Finally, 6 RCTs and 2,037 patients including 953 with advanced or recurrent non-small cell lung cancer (NSCLC) and 1084 with extensive-disease small-cell lung cancer (ED-SCLC) were identified. Among them, 1089 received immunochemotherapy, and 948 patients received chemotherapy alone. Immunochemotherapy can't improve OS (6months: risk ratio (RR)=0.97 P=0.11; 1year: RR=1.05 P=0.36), ORR (RR=1.00 P=0.95) and DCR (RR=0.92, 95%CI 0.85-1.00, P=0.04) of patients with lung cancer compared to pure chemotherapy, but it can improve the PFS (6months: RR=1.16 P=0.02; 1year: RR=1.39 P=0.02) and 6months-irPFS(RR=1.60 P=0.004). However, due to the addition of ipilimumab, the immune-related toxicities are more apparent in immunochemotherapy group.

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“…In the literature there are reports of 64% of patients with both LEMS and SCLC presenting with anti-SOX1 abs, 7 compared with 22-36.5% of patients with SCLC alone. 7,11,15,47 We presume that there were still some patients with LEMS and SCLC among the 30.9% of anti-SOX1 abs patients with unidentified PNS, based on most of them having SCLC. 12,48 Therefore, the actual proportion of patients with LEMS and anti-SOX1 abs should exceed 30.0%.…”

Section: Neurological Disordermentioning

confidence: 90%

“…64 Additionally, 28% of 85 SCLC patients compared with 18% of 210 NSCLC patients had more than 1 ab. 15,64 In the current review, 245 (47.1%) of the 520 patients showed the coexistence of multi- *Data may be overcounted due to overlapping patients from the same database of the Mayo Clinic 64,66 and the Dutch and Spanish databases. 6,7,11,49 , † There were 110 patients with anti-SOX1 abs alone and a total of 116 PNS patients due to coexisting PNS in some patients.…”

Section: Other Coexisting Neural Autoabsmentioning

confidence: 96%

“…ple onconeuronal and cell-surface autoabs at any time point: 213 (41.0%) patients had 2 autoabs, 6,7,11,15,16,20,21,42,[46][47][48][49][52][53][54][55]59,60,[64][65][66] 27 (5.1%) patients had 3 autoabs, 11,15,16,51,53,[56][57][58]64 4 (0.8%) patients had 4 autoabs, 15,16,21,64 and 1 (0.2%) patient had 5 autoabs. 61 In the 285 patients with additional autoabs coexisting with anti-SOX1 abs, anti-VGCCP/Q (n=157, 55.1%) 6,7,11,16,42,48,49,57,64 and anti-Hu (n=73, 25.6%) 7,11,15,16,21,…”

Section: Jcnmentioning

confidence: 99%

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Anti-SOX1 Antibodies in Paraneoplastic Neurological Syndrome

et al. 2020

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Anti-Sry-like high mobility group box (SOX) 1 antibodies (abs) are partly characterized onconeural autoantibodies (autoabs) due to their correlation with neoplastic diseases. Anti-SOX1 abs are associated with various clinical manifestations, including Lambert-Eaton myasthenic syndrome (LEMS) and paraneoplastic cerebellar degeneration (PCD). However, the clinical characteristics of patients with anti-SOX1 abs have not been described in detail. This review systematically explores the reported patients with anti-SOX1 abs and analyzes these cases for demographic characteristics, clinical features, coexisting neuronal autoabs, neuroimaging findings, treatment, and clinical outcomes. In addition, considering that PCD is the most common paraneoplastic neurological syndrome and that the association between PCD and anti-SOX1 abs remains unclear, we focus on the presence of autoabs in relation to PCD and associated tumors. PCD-associated autoabs include various intracellular autoabs (e.g., anti-Hu, anti-Yo, anti-Ri, and anti-SOX1) and cell-surface autoabs (anti-P/Q-type voltage-gated calcium channel). Commonly involved tumors in PCD are small-cell lung cancer (SCLC), gynecological, and breast tumors. LEMS is the most common clinical symptom in patients with anti-SOX1 abs, followed by PCD, and multiple neuronal autoabs coexist in 47.1% of these patients. SCLC is still the predominant tumor in patients with anti-SOX1 abs, while non-SCLC is uncommon. No consistent imaging feature is found in patients with anti-SOX1 abs, and there is no consensus on either the therapy choice or therapeutic efficacy. In conclusion, the presence of anti-SOX1 abs alone is a potential predictor of an uncommon paraneoplastic neurological disorder, usually occurring in the setting of LEMS, PCD, and SCLC. The detection of anti-SOX1 abs contributes to an early diagnosis of underlying tumors, given the diversity of clinical symptoms and the absence of characteristic neuroimaging features.

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Assessment of neuronal autoantibodies in patients with small cell lung cancer treated with chemotherapy with or without ipilimumab

Cited by 28 publications

References 67 publications

Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer

Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer

Efficacy and Safety of Ipilimumab plus Chemotherapy for Advanced Lung Cancer: A Systematic Review and Meta-Analysis

Anti-SOX1 Antibodies in Paraneoplastic Neurological Syndrome

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