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The role of IL-6 in immunotherapy of non-small cell lung cancer (NSCLC) with immune-related adverse events (irAEs).

ABSTRACT: IL-6 is a cytokine that plays an important role in response to injury or infection and is a promising biomarker for predicting poor prognosis and therapeutic targets in non-small cell lung cancer (NSCLC). This article reviews the biochemical mechanism, function and genotype of IL-6, and summarizes the diagnostic and prognostic value of IL-6 level. Anti-IL-6 therapy does not affect the effect of immunocheckpoint inhibitors (ICIs), but enhances its anticancer function, which may be the treatment option for immune-related adverse events (irAEs) in the future. Therefore, IL-6 may be a therapeutic target for the treatment of NSCLC.

SUBMITTER: Ke W

PROVIDER: S-EPMC7113041 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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The role of IL-6 in immunotherapy of non-small cell lung cancer (NSCLC) with immune-related adverse events (irAEs).

Ke Wanhai W Zhang Li L Dai Yan Y

Thoracic cancer 20200211 4

IL-6 is a cytokine that plays an important role in response to injury or infection and is a promising biomarker for predicting poor prognosis and therapeutic targets in non-small cell lung cancer (NSCLC). This article reviews the biochemical mechanism, function and genotype of IL-6, and summarizes the diagnostic and prognostic value of IL-6 level. Anti-IL-6 therapy does not affect the effect of immunocheckpoint inhibitors (ICIs), but enhances its anticancer function, which may be the treatment o ...[more]

PMID: 32043828

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Project description:ImportanceImmune-related adverse events (irAEs) have been associated with the efficacy of PD-1 (programmed cell death protein 1) inhibitors in patients with melanoma, but whether such an association exists for non-small-cell lung cancer (NSCLC) has remained unknown.ObjectiveTo evaluate the relation of irAEs to nivolumab efficacy in NSCLC.Design, setting, and participantsIn this study based on landmark and multivariable analyses, a total of 134 patients with advanced or recurrent NSCLC who were treated with nivolumab in the second-line setting or later between December 2015 and August 2016 were identified from a review of medical records from multiple institutions, including a university hospital and community hospitals. Data were updated as of December 31, 2016.ExposuresThe absence or presence of any irAE before the landmark date.Main outcomes and measuresKaplan-Meier curves of progression-free survival (PFS) according to the development of irAEs in 6-week landmark analysis were evaluated with the log-rank test as a preplanned primary objective. Overall survival (OS) was similarly evaluated. Multivariable analysis of both PFS and OS was performed with Cox proportional hazard regression models.ResultsIn a cohort of 134 patients (median [range] age, 68 [33-85] years; 90 men [67%], 44 women [33%]), irAEs were observed in 69 of the 134 study patients (51%), including 12 patients (9%) with such events of grade 3 or 4, and 24 patients (18%) requiring systemic corticosteroid therapy. In 6-week landmark analysis, median PFS was 9.2 months (95% CI, 4.4 to not reached [NR]) and 4.8 months (95% CI, 3.0 to 7.5) (P = .04) whereas median OS was NR (95% CI, 12.3 to NR) and 11.1 months (95% CI, 9.6 to NR) (P = .01) for patients with or without irAEs, respectively. Multivariable analysis also revealed that irAEs were positively associated with survival outcome, with hazard ratios of 0.525 (95% CI, 0.287 to 0.937; P = .03) for PFS and 0.282 (95% CI, 0.101 to 0.667; P = .003) for OS.Conclusions and relevanceDevelopment of irAEs was associated with survival outcome of nivolumab treatment in patients with advanced or recurrent NSCLC. Further studies are needed to confirm our findings.

Project description:IntroductionPD-(L)1 inhibitors have improved prognosis of non-small-cell lung cancer (NSCLC), but can also cause immune-related adverse events (irAEs) that complicate management.MethodsWe analyzed NSCLC patients receiving PD-(L)1 inhibitors from 2012 to 2020 in a German academic center.ResultsIrAE showed comparable frequencies in stage IV (198/894 or 22%) vs. III (14/45 or 31%, p = 0.15), after anti-PD-(L)1 monotherapy vs. chemoimmunotherapy (139/483 vs. 58/213, p = 0.75), and across treatment lines. In stage IV, irAE occurred after 3.1 months in median, affected multiple organs (median 2) in 27/894 patients and were associated with PD-L1 positivity (25 vs. 14%, p = 0.003), lower neutrophil-to-lymphocyte ratios (29 vs. 17%, p < 0.001 for NLR dichotomized at 5), better ECOG status (26 vs. 18% for 0 vs. 1, p = 0.004), but not related to age, sex, smoking and palliative radiotherapy. Two hundred thirty two irAEs occurred mostly in endocrine glands (4.9%), lungs (4.4%), the musculoskeletal system (4.2%), colon (4.1%), liver (3.7%), and skin (2.6%), while pneumonitis was most frequent with durvalumab following definitive chemoradiation (16% or 7/45, p < 0.01). IrAE severity was grade 1 in 11%, 2 in 41%, 3 in 36%, and 4 in 11% events, while two were lethal (<1%, myocarditis and pneumonitis). Therapy was suspended in 72%, while steroids were initiated in 66% and complemented by other immunosuppressants in 6%, with longest treatment duration for rheumatic events (mean >3 months), and average cumulative prednisone doses >700 mg for all organs, except for skin. Patients developing irAE had longer progression-free (PFS) and overall survival (OS) in multivariable 12/14-week landmark analyses including ECOG status, treatment line, treatment type, PD-L1 TPS, and NLR (median PFS 17 vs. 10 months, HR = 0.68, p = 0.009; median OS 37 vs. 15 months, HR = 0.40, p < 0.001), regardless of grade. OS was longest with skin (95% at 2 years) and shortest with pneumonitis, hepatitis, neurologic, and cardiologic irAE (38, 37, 28, and 0% at 2 years, p < 0.001).ConclusionsApproximately one-fourth of immunotherapy-treated NSCLC patients develop irAEs, most of which necessitate treatment suspension and steroids. Despite more frequent occurrence with PD-L1 positive tumors, lower NLR, and better ECOG PS, irAEs are independently associated with longer survival, especially when affecting the skin. Lethality is below 1%.

Dataset Information

The role of IL-6 in immunotherapy of non-small cell lung cancer (NSCLC) with immune-related adverse events (irAEs).

Publications

The role of IL-6 in immunotherapy of non-small cell lung cancer (NSCLC) with immune-related adverse events (irAEs).

Similar Datasets

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