scholarly journals Peripheral Blood Markers Identify Risk of Immune‐Related Toxicity in Advanced Non‐Small Cell Lung Cancer Treated with Immune‐Checkpoint Inhibitors

2019 ◽  
Vol 24 (8) ◽  
pp. 1128-1136 ◽  
Author(s):  
Alberto Pavan ◽  
Lorenzo Calvetti ◽  
Alessandro Dal Maso ◽  
Ilaria Attili ◽  
Paola Del Bianco ◽  
...  
2021 ◽  
Vol 8 (3) ◽  
pp. 34-43
Author(s):  
A. A. Musaelyan ◽  
A. L. Akopov ◽  
S. V. Lapin ◽  
V. D. Nazarov ◽  
D. I. Fillipov ◽  
...  

Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy have become one of the key approaches in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Evaluation of level of PD-L1 (ligand of the programmed cell death receptor 1) expression on tumor cells using immunohistochemistry is the only approved option for determining the indications of ICIs in this group of patients. However, despite high level of PD-L1 expression, up to 80 % of patients do not respond to therapy due to the presence of primary or acquired resistance, which determines the limited effectiveness of ICI. In addition, 8–17 % of PD-L1-negative patients with NSCLC are also able to respond to ICIs. The limitation of this marker is that it does not allow assessing both intratumoral and systemic immune status. It is necessary to search for additional predictive markers to improve the accuracy of the selection of candidates for immunotherapy, which will avoid costs, wasted time, and a high risk of immune-related adverse events in potentially unresponsive patients. The attention of researchers is devoted to circulating markers in peripheral blood, as a non-invasive alternative to biopsy for predicting and monitoring the response. This review focuses on the most promising immunological markers in peripheral blood as potential predictors of response to ICIs in patients with advanced NSCLC.


2021 ◽  
Vol 16 (3) ◽  
pp. S300-S301
Author(s):  
M. Peravali ◽  
C. Gomes-Lima ◽  
E. Tefera ◽  
M. Baker ◽  
M. Sherchan ◽  
...  

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21047-e21047
Author(s):  
Mohamed Hendawi ◽  
Luke Peterson ◽  
Eyob ale Tadesse ◽  
Frank M. Wolf ◽  
Thomas D. Brown ◽  
...  

e21047 Background: Patients (pts) with lung cancer and other cancers treated with immune checkpoint inhibitors (ICI) may experience immune related adverse events (irAE). These can present with variable severity and with single- or multi-organ involvement including pneumonitis, colitis, hepatitis, and myocarditis/pericarditis. The incidence of myocarditis has been reported between 0.06% and 2.4% and is associated with a high mortality (25% to 50%). This retrospective review of real-world data (RWD) investigates myocarditis as a high-grade adverse event in pts with lung cancer treated with ICIs. Methods: Pts were identified and characterized using RWD in the Syapse Learning Health Network platform from 2010 to 2020 at Advocate Aurora Health Care. Eligible pts included: ≥18 years old; histologically confirmed NSCLC; and myocarditis diagnosis by ICD codes. Additional chart review was performed to confirm timing of ICI treatment and myocarditis. All pts identification and review were performed after IRB review. Results: 12,686 pts with non-small cell lung cancer were eligible for review. The median age at diagnosis was 70; 54% were female; 86% were White and 12% were Black; 1,975 (15.6%) were treated with an ICI and of those 4 cases (0.2%) of myocarditis were identified. All 4 pts were White females, ages 46, 59, 65, and 74 years. Pathology included lung adenocarcinoma (3) and an undifferentiated lung carcinoma (1). All pts had metastatic disease, and none had a prior history of cardiac disease. ICIs were pembrolizumab (2), durvalumab (1), and nivolumab (1). Median time from initial dose of ICI to diagnosis of myocarditis was 62 days [range: 42-185]. All 4 pts presented with chest pain and elevated troponin T [median 0.07 ng/ml (range: 0.06-0.08)]. All pts had echocardiography at the time of diagnosis, and 2 pts had cardiac MRI that confirmed myocarditis. 3 pts were treated with a prednisone taper. 1 pt died of recurrent congestive heart failure and ventricular tachycardia despite rescue attempt with high dose corticosteroids. 2 pts had additional concomitant irAEs of hypothyroidism/colitis, and thyroiditis/pneumonitis, respectively. Conclusions: Many irAEs are reversible. This RWD analysis confirms that clinically evident myocarditis is a rare but serious adverse event of ICI therapy. Early consideration, diagnosis, and intervention may help prevent poor outcomes. Termination of ICI therapy along with initiation of corticosteroids constitute the current standard of management. Further research is warranted to better identify high risk groups, surveillance measures, and improved management of ICI associated myocarditis.


Author(s):  
Ashley E Glode ◽  
Megan B May

Abstract Purpose This article explores the efficacy, toxicity, place in therapy, and considerations for use of recently approved immune checkpoint inhibitors (ICIs) in the treatment of non–small cell lung cancer (NSCLC). Summary Lung cancer is the leading cause of cancer mortality in the United States and is responsible for more cancer-related deaths than breast, prostate, and colorectal cancer combined. The landscape for lung cancer treatment is evolving with the approval of new and exciting novel therapies. Within the last decade numerous ICIs have been approved for use in the management of the most common subtype of lung cancer, NSCLC. The ICI agents currently approved by the Food and Drug Administration (FDA) for use in NSCLC include ipilimumab, pembrolizumab, nivolumab, durvalumab, and atezolizumab. These agents are approved for specific indications; therefore, they are not interchangeable. This review focuses on the landmark trials that led to each FDA-approved indication, as well as common toxicities seen with use of these agents. It also discusses the use of ICIs in special populations and unique considerations prior to initiation of treatment with these novel therapies in a patient with NSCLC. Conclusion ICIs can provide a breakthrough treatment option for the management of NSCLC and are rapidly being adopted into clinical practice. It is important to be familiar with appropriate selection of an ICI therapy option for each patient based on approved indication, unique considerations, and anticipated toxicities.


2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A840-A840
Author(s):  
Lindsey Shantzer ◽  
Sean Dougherty ◽  
Wendy Novicoff ◽  
John Melson ◽  
Daniel Reed ◽  
...  

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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