scholarly journals Neutrophil to lymphocyte ratio influences impact of steroids on efficacy of immune checkpoint inhibitors in lung cancer brain metastases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adam Lauko ◽  
Bicky Thapa ◽  
Mayur Sharma ◽  
Baha’eddin Muhsen ◽  
Addison Barnett ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Neutrophil To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Significant Difference ◽  
The Impact

AbstractSteroids are often utilized to manage patients with non-small cell lung cancer brain metastases (NSCLCBM). Steroids and elevated neutrophil-to-lymphocyte ratio (NLR) have been associated with decreased overall survival (OS) in patients treated with immune checkpoint inhibitors (ICI). We retrospectively investigated patients treated with ICI after the diagnosis of NSCLCBM at a single tertiary care institution examing the impact of steroids and NLR. Overall survival (OS) and intracranial progression-free survival (PFS) were analyzed. 171 patients treated with ICI for NSCLCBM were included. Thirty-six received steroids within 30 days of the start of ICI, and 53 patients had an NLR ≥ 5 before the start of ICI. Upfront steroids was associated with decreased OS on multivariable analysis (median OS 10.5 vs. 17.9 months, p = .03) and intracranial PFS (5.0 vs. 8.7 months, p = .045). NLR ≥ 5 was indicative of worse OS (10.5 vs. 18.4 months, p = .04) but not intracranial PFS (7.2 vs. 7.7 months, p = .61). When NLR and upfront steroids are modeled together, there is a strong interaction (p = .0008) indicating that the impact of steroids depended on the patient’s NLR. In a subgroup analysis, only in patients with NLR < 4 was there a significant difference in OS with upfront steroids (26.1 vs. 15.6 months, p = .032). The impact of steroids on the efficacy of ICI in patients with NSCLCBM is dependent on the patient's NLR underscoring its importance in these patients. Patients with a low NLR, steroid use decreases the efficacy of ICI. These results can inform clinicians about the impact of steroids in patients treated with ICI.

scholarly journals 1769. The Impact of Checkpoint Inhibitor Immunotherapy on Infections in Lung Cancer Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S652-S652
Author(s):  
Alexandre Malek ◽  
Johny Fares ◽  
Melissa Khalil ◽  
Ray Y Hachem ◽  
Anne-Marie Chaftari ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Infectious Complications ◽  
Control Group ◽  
Conventional Chemotherapy ◽  
Significant Difference ◽  
Tract Infections ◽  
The Impact

Abstract Background Immune checkpoint inhibitors (ICI) therapy has ushered cancer treatment into a potentially curative era. However, infectious complications remain largely unknown and the few studies that described infectious complications associated with ICI had no comparative control groups. We assessed the rate of infections in patients with non-small cell lung cancer (NSCLC) treated with ICI plus conventional chemotherapy (CC) vs. CC alone. Methods We performed a comparative single-center retrospective cohort study of patients with NSCLC who received de novo treatment with either Pembrolizumab or Nivolumab, and/or Ipilimumab combined with CC including Pemetrexed and Carboplatin vs. patients treated with CC alone between August 2016 and January 2019. We excluded all patients who were switched from CC to ICI or vice-versa. We evaluated patients’ characteristics, treatment modality, immune-related adverse events (irAEs), and outcome. Infections were defined by clinical signs and symptoms, microbiologic documentation, and/or imaging studies. Results A group of 126 patients who received ICI concurrently with CC were compared with 126 patients who received CC alone (control group). Patients in the ICI group were more likely to have stage IV NSCLC compared with the control group (P < 0.0001). Pembrolizumab was most commonly used as a single ICI agent in 107 patients (85%), followed by Ipilimumab and Nivolumab as dual therapy (9%). Confirmed infections were identified in 20 (16%) patients in the ICI group and 18 (14%) in the control group (P = 0.7). The control group had a higher rate of multiple infections at different times compared with the ICI group (P = 0.014). However, there was no significant difference in the types of infections (bacterial, fungal or viral) that occurred between the two groups. The irAEs were reported in 14 (11%) patients, 13 of them received corticosteroids with a median duration of 32 days (range, 15–64 days). Out of these patients, three (21%) developed confirmed infections of which two were viral upper respiratory tract infections and one was a bacterial urinary tract infection. Conclusion Patients with NSCLC treated with the combination of Immune Checkpoint Inhibitors plus Conventional Chemotherapy have comparable risk of developing infections compared with those on Conventional Chemotherapy alone. Disclosures All authors: No reported disclosures.

scholarly journals THER-14. INFLUENCE OF CLINICAL PARAMETERS ON THE EFFICACY OF IMMUNE CHECKPOINT INHIBITORS IN PATIENTS WITH NON-SMALL CELL LUNG CANCER BRAIN METASTASES (NSCLCBM)

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i13-i13
Author(s):  
Adam Lauko ◽  
Bicky Thapa ◽  
Baha’eddin Muhsen ◽  
Hamid Borghei-Razavi ◽  
Wei Wei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
P Value ◽  
Small Cell Lung

Abstract INTRODUCTION: Non-small cell lung cancer brain metastases (NSCLCBM) patients have a dismal prognosis. Immune checkpoint inhibitors (ICI) have resulted in improved outcomes in a subset of patients, although limited information exists on the impact of ICI in patients with NSCLCBM. METHODS: We reviewed 121 NSCLCBM (2012–2018) patients treated at our tertiary care center. All patients received at least 2 cycles of ICI therapy after diagnosis of NSCLCBM. Overall survival (OS) and progression-free survival (PFS) were calculated from the start of ICI therapy to date of death, progression or last follow up. Kaplan-Meier curves were used to estimate survival and were analyzed using the Wilcoxon test. RESULTS: Median age was 62 years (39–81) and median KPS was 90. Eighty-six patient received Nivolumab, 7 Atezolizumab, 25 Pembrolizumab, and 3 patients received multiple ICI over the course of their treatment for NSCLCBM. One hundred and twelve patients underwent stereotactic radiosurgery. Nine patients were treated with ICI alone and 25 patients underwent surgical resection. Median OS for the entire cohort was 558 (303–1159) days and median PFS was 220 (114–512) days. Twenty-four patients received oral steroids within the first 28 days of ICI (median prednisone equivalent dose of 27 mg). Patients on upfront steroid therapy had a median PFS of 148 days vs 301 days in patients not on upfront steroids (p-value .0095). Complete blood count at the start of ICI was available for 87 patients and neutrophil to lymphocyte ratios (NLR) were calculated. Patients with NLR at the start of ICI above 5 (n=33) had a median overall survival of 337 days compared to 558 days when NLR was below 5 (p-value .038). CONCLUSION: Use of steroids at initiation or within first 28 days of ICI therapy and NLR of greater than 5 are associated with worse outcomes in NSCLCBM treated with ICI.

Neutrophil to Lymphocyte ratio (NLR): A prognostic marker in melanoma patients receiving immunotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9573-9573
Author(s):  
Richard Thomas O'Dwyer ◽  
Colum Dennehy ◽  
Jane Sze Yin Sui ◽  
Catherine Margaret Kelly ◽  
Paula Calvert ◽  
...  
Keyword(s):  
Prognostic Marker ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Neutrophil To Lymphocyte Ratio ◽  
Rank Test ◽  
Continuous Variables ◽  
Lymphocyte Ratio ◽  
Significant Difference

9573 Background: Cancer related inflammatory processes have been shown to have an important role in tumourigenesis, disease progression, and patient prognosis. An elevated neutrophil to lymphocyte ratio (NLR) is associated with a worse outcome in several malignancies. The relationship between NLR and immune checkpoint blockade is poorly understood. We sought to investigate the role of NLR in patients receiving immune checkpoint inhibitors for metastatic melanoma (MM). We aimed to do this by comparing outcomes of patients with MM with high ( > 3) and low ( < 3) NLRs receiving immunotherapy, and investigating whether NLR acts as a prognostic biomarker. Methods: We performed a retrospective review of electronic medical records and collected data on 40 patients with MM treated with immunotherapy from 2013 to 2018 in MMUH, Dublin. NLR was defined as absolute neutrophil count divided by absolute lymphocyte count. Continuous variables were expressed as a median. We examined NLR at baseline and at 6 weeks (+-2 weeks). We also examined percentage change in NLR. These parameters were tested for association with PFS and OS using the log rank test. Results: 40 patients received immune checkpoint inhibitors in the form of ipilimumab, nivolumab, and pembrolizumab. The median age was 61.2 ( 29.7 to 77.1). The median baseline NLR was 3.39 ( 1.05 to 26.03). The median NLR at 6 weeks (+-2 weeks) was 2.86 ( 0.83 to 19.9). The median change in NLR was -8.02% (- 80.99% to 409.38%). Median time to progression was 4.7 months (0.4 to 51.4 months). Overall survival was 12.9 months (0.4 to 67.7 months). When baseline NLR < 3 patients had a significantly longer PFS: 11.7 vs 2.8 months (p = 0.02). When NLR at approximately 6 weeks was < 3, patients also had significantly longer PFS: 10.8 vs 2.9 months (p = 0.04). When NLR decreased by > 20% from baseline, there was no significant difference in PFS (p = 0.82). When NLR < 3, patients had significantly longer OS: 18 months vs 8.2 months (p = 0.02). When NLR at approximately 6 weeks was < 3, patients had significantly longer OS: 20.3 months vs 7.4 months (p = 0.003). Conclusions: Baseline NLR < 3 and NLR < 3 approximately 6 weeks after initiation of treatment is associated with improved PFS and OS. Change in NLR after initiation of treatment is not significantly associated with improved outcomes, however our sample size was small. NLR may be used as a readily available and cheap prognostic marker in MM patients receiving immunotherapy.

scholarly journals Astragalus Polysaccharide Injection (PG2) Normalizes the Neutrophil-to-Lymphocyte Ratio in Patients with Advanced Lung Cancer Receiving Immunotherapy

2021 ◽  
Vol 20 ◽  
pp. 153473542199525
Author(s):  
Shih Ming Tsao ◽  
Tz Chin Wu ◽  
JiZhen Chen ◽  
Feichi Chang ◽  
Thomos Tsao
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Treatment Initiation ◽  
Checkpoint Inhibitors ◽  
Neutrophil To Lymphocyte Ratio ◽  
Advanced Lung Cancer ◽  
Control Group ◽  
Lymphocyte Ratio ◽  
Astragalus Polysaccharide

Objectives: The neutrophil-to-lymphocyte ratio (NLR) is a prognostic marker in patients with cancer receiving immunotherapy. Recent studies have shown that a high NLR was associated with a poor response and decreased survival. However, there is no intervention to reverse abnormally high NLR and improve clinical outcomes. Astragalus polysaccharide injection (PG2) is an immunomodulatory therapy for cancer-related fatigue. This study aimed to examine whether PG2 might normalize the NLR and affect the overall survival of patients with lung cancer treated with immunotherapy. Materials and Methods: We retrospectively examined the medical records of patients with lung cancer treated with immune checkpoint inhibitors (ICIs) between October 1, 2015 and November 30, 2019. All patients received ICI combination chemotherapies, and some similarly received PG2 (Control vs PG2). The NLR was assessed before treatment and 6 weeks after ICI initiation, and the survival data was collected at least 4 years after treatment initiation for the first enrolled patient. Results: Fifty-three patients were included. Six weeks after ICI initiation, 91.3% of the patients in the PG2 group exhibited a predefined “Decrease or no change” in the NLR, which was 28% higher than that in the Control group (63.3%) ( P = .028). The NLR significantly decreased by 31.60% from baseline in the PG2 group ( P = .012), whereas it increased by 5.80% in the Control group ( P = .572). Six weeks after ICI treatment initiation, both groups had a median NLR of 3.73, and the overall survival was also similar (PG2 vs Control, 26.1 months vs 25.4 months, respectively); however, the PG2 group had a higher median baseline NLR than the Control group (PG2 vs Control, 4.51 vs 2.81, respectively). Conclusion: This study demonstrated that PG2 could normalize the NLR in patients with lung cancer receiving ICI combination treatments.

Age affects the efficacy of immune checkpoint inhibitors in patients with advanced cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2638-2638
Author(s):  
Yongjie Wang ◽  
Ronghua Yang ◽  
Dong Wang ◽  
Donghua Zhao ◽  
Peng Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Older Patients ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Sign Test ◽  
Patients With Cancer ◽  
The Impact ◽  
Effect Of Age

2638 Background: Immune checkpoint inhibitors (ICIs), such as programmed death(ligand)1 (PD-(L)1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, have dramatic effects on treatment in patients with various malignancies. High tumor mutation burden (TMB) is predictive of clinical response to ICI in multiple cancer types. Although age-related immune dysfunction might induce difference on the efficacy of ICIs between younger and older patients, the potential effect of age on the efficacy of ICIs remains little known and controversial. Herein, we aimed to analysis the association between age and the efficacy of ICIs based on MSKCC cohort. Methods: We screened out 1661 patients having complete information with advanced cancer, whose tumors underwent next-generation sequencing (NGS) detection and who were treated with at least one dose of ICI in MSKCC cohort. All patients were divided into two groups according to age, the younger group (age ≤50-year old) and the older group (age > 50-year old). We further analyzed the differences in overall survival (OS) and TMB between the two groups. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated via Cox regression model for OS and P-values were calculated via the Wilcoxon sign test for TMB. We analyzed the effect of age on ICI in lung cancer using the same way. Results: In 1661 patients with cancer in our study, 312 (19%) younger and 1349 (81%) older patients were found. The pooled HRs for OS was 1.28 (95% CI: 1.09-1.52) in younger group compared with older group. In 1661 patients with cancer, there was 350 (21%) patients with lung cancer, including 30 (9%) younger and 320 (91%) older patients. The pooled HRs for OS was 1.45 (95% CI: 0.95-2.23) in younger group compared with older group in lung cancer. In addition, TMB in older group was higher than in younger group and significant difference of TMB was found via the Wilcoxon sign test (p = 2.6e-10) between the two groups, especially in lung cancer (p = 1e-4). Conclusions: Our study assessed the impact of age on the efficacy of ICIs using the threshold of 50 years old for the first time and we founded that patients in older group had higher TMB and longer OS than younger group.

The Current Role of Immunotherapy in mCRPC: A Systematic Review

2021 ◽  
Vol 8 (7) ◽  
Author(s):  
Dalibey H ◽  
◽  
Hansen TF ◽  
Zedan AH ◽  
◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Specific Antigen ◽  
Treatment Modalities ◽  
Significant Difference

Background: The development of immunotherapy has shown promising results in several malignant diseases, including prostate cancer, calling for a systematic review of the current literature. This review aims to evaluate the present data and prospects of immune checkpoint inhibitors in metastatic Castration Resistant Prostate Cancer (mCRPC). Methods: Articles were identified via a systematic search of the electronic database Pubmed, in accordance with the PICO process and following the PRISMA guidelines. Articles in English studying immune checkpoint inhibitors in patients with mCRPC published between March 2010 and March 2020 were eligible for inclusion. Endpoints of interest were Overall Survival (OS), Progression-Free Survival (PFS), clinical Overall Response Rate (ORR), and Prostate-Specific Antigen (PSA) response rate. Results: Ten articles were identified as eligible for inclusion. The studies primarily explored the use of Ipilimumab, a CTLA-4 inhibitor, and Pembrolizumab, a PD-1 inhibitor. These drugs were both used either as monotherapy or in combination with other treatment modalities. The largest trial included in the review demonstrated no significant difference in overall survival between the intervention and placebo. However, two studies presented promising data combing immunotherapy and immune vaccines. Grade 3 and 4 adverse events ranging from 10.1% to 82.3%, whit diarrhea, rash, and fatigue were the most frequently reported. Forty relevant ongoing trials were identified exploring immunotherapy with or without a parallel treatment modality. Conclusion: Overall, the current data shows that the effect of immune checkpoint inhibitors as monotherapy may have limited impact on mCRPC, and the results from ongoing combinational trials are eagerly awaited.

scholarly journals 803 Immune-related adverse events correlate with improved outcomes in patients with advanced non-small cell lung cancer treated with combinations of immune-checkpoint inhibitors and chemotherapy

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A840-A840
Author(s):  
Lindsey Shantzer ◽  
Sean Dougherty ◽  
Wendy Novicoff ◽  
John Melson ◽  
Daniel Reed ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung

BackgroundImmune checkpoint inhibitors (ICIs) have become the backbone of treatment for most driver-mutation negative, advanced non-small cell lung cancers. ICIs have been approved both as monotherapy and in combination with chemotherapy for front line management. While ICIs are generally regarded as well-tolerated, an unintended activation of the immune system can result in a variety of immune-related adverse events (irAEs), which can limit their use in severe cases. In patients with NSCLC treated with ICI monotherapy, the occurrence of an irAE and the development of multisystem irAEs have been associated with improved clinical outcomes, suggesting irAE occurrence could have prognostic implications.1–4 However, in patients treated with combination immunotherapy plus chemotherapy, the correlation between irAEs and survival has not been completely elucidated.MethodsWe conducted a retrospective chart review of 94 patients with advanced NSCLC treated with a combination of ICI plus chemotherapy between 2015 and 2021 to evaluate for a correlation between irAE occurrence and overall survival (OS). Patients were divided into two groups: those who experienced at least one irAE and those who did not experience an irAE. To account for immortal time bias, we conducted landmark analyses at 12 and 24 weeks. We additionally investigated the impact of multisystem irAEs on clinical outcomes and described the profile of irAEs observed at our institution.ResultsAmong the 94 evaluable patients identified in our population, 43.6% experienced at least one irAE. Of those patients who experienced an irAE, 26 (63.4%) experienced a single irAE, 9 (22.0%) experienced 2 irAEs, and 6 (14.6%) experienced 3 or more irAEs. The most commonly observed irAEs were dermatitis followed by pneumonitis and colitis. In our cohort, patients with at least one irAE had significantly longer median OS (16.8 mos vs 9.8 mos) compared to those who did not experience an irAE (HR 0.51, 95% CI 0.43–0.76, p=0.011) (figure 1). Landmark survival analyses at 12 and 24 weeks continued to support significant differences in median OS based on presence or absence of an irAE (HR 0.49, 95% CI 0.24–0.46, and HR 0.45, 95% CI 0.21–0.60 respectively). Among patients with at least one irAE, the subset of patients who experienced multiple irAEs had further improved median OS compared to those with a single irAE.ConclusionsIn patients with advanced NSCLC treated with combination ICI plus chemotherapy, the occurrence of an irAE is associated with improved overall survival.ReferencesTeraoka S, Fujimoto D, Morimoto T, et al. Early Immune-related adverse events and association with outcome in advanced non-small cell lung cancer patients treated with Nivolumab: a prospective cohort study. Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer 2017;12(12):1798–1805. doi:10.1016/j.jtho.2017.08.022.Ricciuti B, Genova C, De Giglio A, et al. Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis. Journal of Cancer Research and Clinical Oncology 2019;145(2):479–485. doi:10.1007/s00432-018-2805-3.Toi Y, Sugawara S, Kawashima Y, et al. Association of immune-related adverse events with clinical benefit in patients with advanced non-small-cell lung cancer treated with nivolumab. The Oncologist. 2018;23(11):1358–1365. doi:10.1634/theoncologist.2017-0384.Shankar B, Zhang J, Naqash AR, et al. Multisystem immune-related adverse events associated with immune checkpoint inhibitors for treatment of non-small cell lung cancer. JAMA Oncol 2020;6(12):1952–1956. doi:10.1001/jamaoncol.2020.5012Ethics ApprovalThis research study obtained ethics approval by the institutional review board at the University of Virginia, IRB# 19083.Abstract 803 Figure 1Overall Survival by presence or absence of an irAE in patients with advanced lung cancer treated with immune checkpoint inhibitors plus chemotherapy

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