scholarly journals Commentary: Breaking down non–small cell lung cancer tumor microenvironment heterogeneity and predicting response to immune checkpoint inhibitors

2020 ◽  
Vol 159 (4) ◽  
pp. 1612-1613
Author(s):  
Joshua Boys ◽  
Mark Onaitis
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cancer Tumor

Myocarditis as a rare, yet serious adverse event associated with immune checkpoint inhibitors in patients with non-small cell lung cancer: Case series from a large community-based cancer center.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21047-e21047
Author(s):  
Mohamed Hendawi ◽  
Luke Peterson ◽  
Eyob ale Tadesse ◽  
Frank M. Wolf ◽  
Thomas D. Brown ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Event ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Serious Adverse Event

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.

Immune checkpoint inhibitors: Significant advancements in non–small cell lung cancer treatment

2021 ◽  
Author(s):  
Ashley E Glode ◽  
Megan B May
Keyword(s):  
Lung Cancer ◽  
Cancer Treatment ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Novel Therapies ◽  
Small Cell Lung

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.

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

scholarly journals 237 Infectious complications in patients with non-small cell lung cancer treated with anti-PD(L)1 immune checkpoint inhibitors

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A253-A253
Author(s):  
Matthew Guo ◽  
Aanika Balaji ◽  
Joseph Murray ◽  
Joshua Reuss ◽  
Seema Mehta Steinke ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Infectious Complications ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

BackgroundImmune checkpoint inhibitors (ICI) are standard treatment for stage III/IV non-small cell lung cancer (NSCLC). ICIs may cause immune-related adverse events (irAEs) often requiring corticosteroids or other immunosuppressive therapy and are associated with increased risk of opportunistic infections.1 2 The burden of infectious complications in NSCLC patients (pts) treated with ICIs is poorly described.MethodsWe retrospectively reviewed NSCLC pts treated with ICIs between 2016–2020 at a large tertiary academic center. An infectious complication related to ICIs was defined as a pathogen-confirmed or clinically diagnosed infection requiring antimicrobials during or within 3 months of ICI discontinuation. High-grade infections were defined as those requiring IV antibiotics (grade 3), life-threatening or requiring ICU stay (grade 4), or resulting in death (grade 5). irAEs were defined by the treating provider and treated according to standard guidelines. Patient demographics, treatment data, cancer outcomes, infectious complications, and irAE details were annotated in an IRB-approved database. An AE treated as both an infection and/or irAE with antibiotics and immunosuppression was coded as a concomitant irAE/infection event. The association between patient features and infectious complications was examined using logistic regression. Treatment and disease characteristics for concomitant irAE with infection were also described.Results302 ICI-treated NSCLC pts were included. 211 pts received PD-1 monotherapy and 91 received PD-1 therapy with CTLA-4 therapy, chemotherapy, or other investigational therapy. The majority (175/302, 57.9%) had a documented infection (bacterial=138, viral=17, fungal=19, mycobacterial=1) during or within 3 months of ICI discontinuation. Grade ≥3 infections occurred in 33.4% of pts (101/302). Pulmonary infections were most common (35.4%), followed by gastrointestinal, urinary, and skin (<10%, each). A subset of pts were treated as having concomitant irAE/infection events (63/302, 20.9%). Among 63 pts who experienced irAEs, pneumonitis occurred most commonly (47/63, 74.6%) followed by colitis (7/63, 11.1%); other irAEs (hepatitis, myocarditis, thyroiditis) occurred in <3 patients each. A concomitant event was associated with a trend toward higher odds of hospitalization (OR 3.91, CI 0.5–30.76) when adjusted for grade ≥3 infection. Similarly, steroid use within one month prior to infection, was also associated with a trend toward higher odds of hospitalization (OR 8.88, CI 0.81–97.15), adjusted for grade ≥3 infection.ConclusionsIn this retrospective study of NSCLC pts treated with ICIs, the majority experienced infections during or within 3 months of ICI discontinuation. The most common infections were bacterial pulmonary in origin. Concomitant irAE/infection was associated with trend toward higher odds of hospitalization.ReferencesHamashima R, Uchino J, Morimoto Y, et al. Association of immune checkpoint inhibitors with respiratory infections: a review. Cancer Treatment Reviews 2020;90:102109. doi:10.1016/j.ctrv.2020.102109Lu M, Zhang L, Li Y, et al. Recommendation for the diagnosis and management of immune checkpoint inhibitor related infections. Thorac Cancer 2020;11(3):805–809. doi:10.1111/1759-7714.13313Ethics ApprovalThis retrospective chart review study has obtained ethics approval from the Institutional Review Board at the Johns Hopkins School of Medicine (number: IRB00129424).

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