scholarly journals 9P HLA-I homozygosity as a predictive biomarker for developing immune related adverse events (irAE) among non-small cell lung cancer (NSCLC) patients treated with single agent immunotherapy

2021 ◽  
Vol 32 ◽  
pp. S1378
Author(s):  
A. Abed ◽  
N. Law ◽  
L. Calapre ◽  
S. Bowyer ◽  
M. Millward ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Single Agent ◽  
Predictive Biomarker ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

scholarly journals 25 Potential role of serum proteome in predicting immune-related adverse events from immunotherapy in non-small cell lung cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A29-A29
Author(s):  
Leeseul Kim ◽  
Young Kwang Chae ◽  
Dong-Uk Lee
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Primary Immune Response ◽  
Small Cell Lung ◽  
Serum Proteome ◽  
Proteome Level ◽  
Nsclc Patients

BackgroundPredicting immune-related adverse events (irAEs) in early stage is being emphasized even more. Host response to disease is reflected in serum proteome level and that allows serum proteome level as a new marker to explore response to immunotherapy. With the help of a serum-based proteomics test, Primary Immune Response (PIR), we are accessing the correlations between developing irAEs and immunotherapy in non-small cell lung cancer (NSCLC) patients.MethodsData of 48 consented NSCLC patients with baseline PIR test done within one week prior to the start of immunotherapy were collected. Samples were grouped into either sensitive or intermediate/resistant (not sensitive) by PIR classification. We analyzed the durations from the immunotherapy initiation to the first episode of irAE. IrAEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.ResultsAmong the 48 NSCLC patients, 19 patients (39%) experienced one or more irAEs with the majority classified as either grade 1 (n=7, 36%) or grade 2 (n=10, 52%). PIR-sensitive group showed no difference in irAE free period compared to PIR-not sensitive (p=0.92, HR=0.95, 95% CI=00.3212 to 2.834). The median ‘Time to first irAE’ were undefined and 24 in PIR-sensitive and PIR-not sensitive, respectively.ConclusionsOur results demonstrated PIR-sensitive patients are not likely to tolerate immunotherapy longer without developing irAEs.

scholarly journals Therapeutic and Prognostic Implications of Immune-Related Adverse Events in Advanced Non-Small-Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Lea Daniello ◽  
Mariam Elshiaty ◽  
Farastuk Bozorgmehr ◽  
Jonas Kuon ◽  
Daniel Kazdal ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Palliative Radiotherapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Treatment Type ◽  
Nsclc Patients

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%.

scholarly journals Vinorelbine in Non-Small Cell Lung Cancer: Real-World Data From a Single-Institution Experience

2020 ◽  
Vol 28 (3) ◽  
pp. 237-248
Author(s):  
Stefania Nobili ◽  
Daniele Lavacchi ◽  
Gabriele Perrone ◽  
Giulio Vicini ◽  
Renato Tassi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Real World ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Single Institution ◽  
Nsclc Patients ◽  
Combination Regimens

The use of vinorelbine as a single agent or in combination regimens in non-small cell lung cancer (NSCLC) is associated with satisfactory clinical activity. However, the role of vinorelbine-based chemotherapy in chemonaive locally advanced unresectable or metastatic NSCLC patients, according to real-world treatment patterns, has still not been widely explored. Eighty-one patients treated at a single institution were retrospectively analyzed. Thirty-seven received standard first-line single-agent vinorelbine, and 44 received vinorelbine plus platinum drugs, based on physician’s choice; 61.7% were older than 70 years, and 60.5% were affected by ≥2 comorbidities. Sixty-three patients were evaluable for objective response: 22% achieved partial response and 41% stable disease. Median progression-free survival (PFS) was 5.4 months. A benefit in PFS was observed in patients treated with combinations vs. single-agent vinorelbine (6.7 vs. 3.5 months, p = 0.043). Median overall survival (OS) was 10.4 months without a statistically significant difference between treatments (12.4 vs. 7.5 months). In 55 stage IV patients, OS was positively correlated with combination regimens, M1a stage, or ≤2 metastatic lesions. Grade 3‐4 toxicity occurred in 33% of patients, and dose reduction in 11%. A statistically significant higher incidence of toxicity was observed in patients receiving combinations, in women, in patients younger than 75 years, or patients with metastases. In this real-word analysis, we confirmed the efficacy and tolerability of vinorelbine as a single agent or combined with platinums in patients usually underrepresented in controlled clinical trials. Single-agent vinorelbine may represent a suitable option in elderly or unfit NSCLC patients and warrants investigation as a potential drug candidate for immunochemotherapy combination regimens.

scholarly journals Efficacy and toxicities of combination maintenance therapy in the treatment of advanced non-small-cell lung cancer: an up-to-date meta-analysis

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Jianming Hu ◽  
Jiawei Hu ◽  
Xiaolan Liu ◽  
Long Li ◽  
Xue Bai
Keyword(s):  
Lung Cancer ◽  
Maintenance Therapy ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3 ◽  
Nsclc Patients

Abstract Background: Single agent maintenance therapy has been approved for the treatment of advanced non-small-cell lung cancer (NSCLC) due to its potential survival benefits, but whether combined maintenance therapy would improve the survival of advanced NSCLC remains undetermined. Methods: Relevant trials were identified by searching electronic databases and conference meetings. Prospective randomized controlled trials (RCTs) assessing combination maintenance therapy in advanced NSCLC patients were included. Outcomes of interest included overall survival (OS), progression-free survival (PFS), and grade 3–4 toxicities. Results: A total of 1950 advanced NSCLC patients received combination maintenance treatment from six trials were included for analysis. The use of doublet maintenance therapy in NSCLC patients significantly improved PFS (HR 0.74, 95%CI: 0.59–0.93, P = 0.010), but not for OS (HR 0.95, 95%CI: 0.85–1.07, P = 0.40) in comparison with single agent maintenance therapy. Similar results were observed in sub-group analysis according to treatment regimens. In addition, there was no significantly risk difference between doublet and single agent maintenance therapy in terms of grade 3/4 hematologic and non-hematologic toxicities. Conclusion: The findings of the present study show that doublet combination maintenance therapy is superior to single agent maintenance therapy in terms of PFS, without increased grade 3–4 toxicities. Future prospective studies are recommended to clearly assess the long-term clinical benefit of doublet maintenance therapy and its impact on health-related quality of life.

Association of relative neutrophilia with a distinct immunoinhibitory milieu in non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14047-e14047
Author(s):  
Kyle Gregory Mitchell ◽  
Lixia Diao ◽  
Hai T. Tran ◽  
Marcelo Vailati Negrao ◽  
Tatiana Karpinets ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Complete Blood Count ◽  
Lymphocyte Activation ◽  
Predictive Biomarker ◽  
Gene Signature ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

e14047 Background: Elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with poor prognosis in non-small cell lung cancer (NSCLC); the biological underpinnings of this observation have not been fully elucidated. We examined the relationships between peripheral neutrophil counts (PMN), NLR, circulating cytokines and angiogenic factors (CAF), and tumor microenvironment (TME) features in NSCLC. Methods: 150 patients with resectable NSCLC were enrolled in an immunoprofiling project. A panel of 43 CAFs was used to analyze preoperative plasma samples. Chemotherapy-naïve patients with CAF and a complete blood count ≤30 days preoperatively were included (n = 66; Table). For a subset, transcriptional signatures (MCP-counter, n = 50) and flow cytometry (n = 19) were used to identify TME phenotypes. Results: Increased PMNs were associated with increased pro-inflammatory CAF such as IL-1b (r = 0.392) and IL-6 (r = 0.339), as well as Th17/Tc17 associated CAF IL-17A (r = 0.320) and TNF-a (r = 0.368). Elevated NLR was inversely correlated with the lymphocyte activation marker soluble CD27 (r = -0.320, p = 0.009). This negative association was mirrored in the TME, as tumor neutrophil signatures were inversely correlated with a local IFN-g gene signature (r = -0.626, p < 0.001). Interestingly, a Th17/Tc17 peripheral signature (elevated IL-17A) was associated with an enrichment of CD8+TIM3+ cells (r = 0.623, p = 0.042) in the tumor. While this requires confirmation in a larger cohort, this correlation provides a potential rationale for targeting TIM3 in this population. Upon analysis of clinical characteristics, peripheral PMNs and NLR were higher among patients with squamous histology (PMN p = 0.009; NLR p = 0.034) and positively correlated with tumor size (PMN r = 0.344, p = 0.004; NLR r = 0.363, p = 0.003). Conclusions: A relative neutrophilia in NSCLC patients is associated with an inflammatory milieu suggestive of a Th17/Tc17 presence and decreased lymphocyte activation that is reflected within the TME. Further investigation is needed to define the role of NLR as a predictive biomarker and to identify whether neutrophils or Th17/Tc17 T cells could serve as a therapeutic target to improve immunotherapy response in NSCLC.[Table: see text]

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