scholarly journals A case report of immune-related pneumonitis after combined treatment of non small cell lung cancer

2020 ◽  
pp. 258-264
Author(s):  
E. S. Denisova ◽  
M. S. Ardzinba ◽  
K. K. Laktionov ◽  
D. I. Yudin ◽  
K. A. Sarantseva ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Combined Treatment ◽  
Left Lung ◽  
Immune Checkpoints ◽  
Results Of Treatment ◽  
Predictors Of Response ◽  
High Doses

Immunotherapy is the most promising method in the treatment of lung cancer, especially in connection with the rapidly growing development of monoclonal antibodies aimed at inhibiting immune checkpoints: anti-CTLA-4, anti-PD-1, anti-PD-L1. Classic immuno-mediated adverse events that occur with this method of treatment can affect several organs, including the lungs. Pneumonitis is a potentially life-threatening complication and often requires rapid treatment with high doses of corticosteroids and antibacterial drugs. We present the case of a 67-year-old patient with primary multiple malignant tumors of the larynx and left lung after combined treatment and incomplete treatment with Nivolumab, complicated by immuno-mediated pneumonitis. This report highlights the importance of treating patients with contraindications to chemotherapy when specific antitumor treatment is required, as well as timely detection of a rare but dangerous adverse event: immuno-mediated pneumonitis that occurs during treatment with immune checkpoint inhibitors. Thus, knowing the frequency of adverse events when using PD-1 and PD-L1 inhibitors, as well as the possible presence of comorbidities in patients, will make it easier for doctors to make informed decisions in the treatment of patients, and understanding the interaction of the tumor and the immune system will help determine the best predictors of response and further improve the results of treatment of patients with NSCLC.

scholarly journals The use of atezolizumab in combination with chemotherapy in first-line of metastatic small cell lung cancer. Case report

2021 ◽  
Vol 23 (2) ◽  
pp. 292-298
Author(s):  
Nikolai A. Ognerubov ◽  
Tatyana S. Antipova
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Left Lung ◽  
Disease Free Survival ◽  
Small Cell ◽  
Cancer Case ◽  
Malignant Neoplasms ◽  
First Line ◽  
Therapy Regimen

Background. Lung cancer (LC) occupies a leading position among malignant tumors in the world, it accounts for 11.4% of the total malignant neoplasms. In 2020, there were 2 206 771 new cases of LC and 1 796 144 deaths worldwide. Among the histological variants, small cell LC (SCLC) has the most unfavorable outcomes. This variant is considered highly sensitive to chemotherapy. Despite some successes in the treatment of this disease, the results of treatment remain problematical. In recent years, the use of immune checkpoint inhibitors has provided significant control of the course of the disease. Aim. To show the efficacy of atezolizumab in combination with chemotherapy in patients with metastatic SCLC. Materials and methods. A 76-year-old patient with left lung cancer, IVA T4N3M1b, the right supraclavicular lymph node metastases, exudative pleuritis of the left lung was under observation. The histological investigation showed SCLC. Brain metastases were not detected. ECOG 0. Results. The patient was treated using atezolizumab 1200 mg in combination with carboplatin 5 AUC and etoposide 100 mg/m2 on days 1, 2, 3 for four cycles, followed by a maintenance therapy regimen with atezolizumab 1200 mg every 21 days. The patient received 21 injections during 14 months. The assessment of treatment effect was evaluated using combined 18F-fluorodeoxyglucose positron emission and X-ray computed tomography. As a result of the treatment, after 7 months, a complete clinical and morpho-metabolic regression of the tumor was reached, which persisted throughout the period of the treatment. Among the adverse events were detected grade 2 anemia and first-stage sensory neuropathy. No immune-related adverse events were observed. Conclusion. The addition of atezolizumab to etoposide + carboplatin as the first-line therapy for extensive-stage SCLC provides the long-term overall and disease-free survival with achieving the satisfactory quality of life in patients and acceptable drug tolerance.

scholarly journals Rheumatic Immune-Related Adverse Events—A Consequence of Immune Checkpoint Inhibitor Therapy

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 561
Author(s):  
Anca Bobircă ◽  
Florin Bobircă ◽  
Ioan Ancuta ◽  
Alesandra Florescu ◽  
Vlad Pădureanu ◽  
...  
Keyword(s):  
Immune System ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Multidisciplinary Approach ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Cancer Cell Growth ◽  
Inhibitory Mechanisms ◽  
Checkpoint Inhibitor Therapy

The advent of immunotherapy has changed the management and therapeutic methods for a variety of malignant tumors in the last decade. Unlike traditional cytotoxic chemotherapy, which works by interfering with cancer cell growth via various pathways and stages of the cell cycle, cancer immunotherapy uses the immune system to reduce malignant cells’ ability to escape the immune system and combat cell proliferation. The widespread use of immune checkpoint inhibitors (ICIs) over the past 10 years has presented valuable information on the profiles of toxic adverse effects. The attenuation of T-lymphocyte inhibitory mechanisms by ICIs results in immune system hyperactivation, which, as expected, is associated with various adverse events defined by inflammation. These adverse events, known as immune-related adverse events (ir-AEs), may affect any type of tissue throughout the human body, which includes the digestive tract, endocrine glands, liver and skin, with reports of cardiovascular, pulmonary and rheumatic ir-AEs as well. The adverse events that arise from ICI therapy are both novel and unique compared to those of the conventional treatment options. Thus, they require a multidisciplinary approach and continuous updates on the diagnostic approach and management.

scholarly journals Expanded human NK cells from lung cancer patients sensitize patients’ PDL1−negative tumors to PD1-blockade therapy

2021 ◽  
Vol 9 (1) ◽  
pp. e001933
Author(s):  
Sophie M Poznanski ◽  
Tyrah M Ritchie ◽  
Isabella Y Fan ◽  
Abdullah El-Sayes ◽  
Ana L Portillo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Nk Cells ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Combined Treatment ◽  
Death Receptor ◽  
High Rate ◽  
Advanced Lung Cancer ◽  
Pd1 Blockade

Lung cancer remains the leading cause of cancer death worldwide despite the significant progress made by immune checkpoint inhibitors, including programmed death receptor-1 (PD1)/PD ligand 1 (PDL1)-blockade therapy. PD1/PDL1−blockade has achieved unprecedented tumor regression in some patients with advanced lung cancer. However, the majority of patients fail to respond to PD1/PDL1 inhibitors. The high rate of therapy non-response results from insufficient PDL1 expression on most patients’ tumors and the presence of further immunosuppressive mechanisms in the tumor microenvironment. Here, we sensitize non-responding tumors from patients with lung cancer to PD1-blockade therapy using highly cytotoxic expanded natural killer (NK) cells. We uncover that NK cells expanded from patients with lung cancer dismantle the immunosuppressive tumor microenvironment by maintaining strong antitumor activity against both PDL1+ and PDL1− patient tumors. In the process, through a contact-independent mechanism involving interferon γ, expanded NK cells rescued tumor killing by exhausted endogenous TILs and upregulated the tumor proportion score of PDL1 across patient tumors. In contrast, unexpanded NK cells, which are susceptible to tumor-induced immunosuppression, had no effect on tumor PDL1. As a result, combined treatment of expanded NK cells and PD1-blockade resulted in robust synergistic tumor destruction of initially non-responding patient tumors. Thus, expanded NK cells may overcome the critical roadblocks to extending the prodigious benefits of PD1-blockade therapy to more patients with lung cancer and other tumor types.

scholarly journals P33.14 STK11/LKB1, KRAS Mutations and Immune-Related Adverse Events as Predictors of Response to Immunotherapy in Lung Cancer

2021 ◽  
Vol 16 (3) ◽  
pp. S411
Author(s):  
L. Raez ◽  
R. Uba ◽  
A. North ◽  
K. Dumais ◽  
H. Powery ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Kras Mutations ◽  
Predictors Of Response

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 Immunotherapy for Advanced Small Cell Lung Cancer: A Case Report

2021 ◽  
Vol 6 (5) ◽  
Author(s):  
Wang J ◽  
Deng C ◽  
Zhu X ◽  
Zou X ◽  
Wang J
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Malignant Tumors ◽  
Small Cell ◽  
Immune Checkpoints ◽  
Small Cell Lung ◽  
Advanced Stages ◽  
Made In

In recent years, extraordinary achievements have been made in treating tumor immune checkpoints as targets, which significantly contributes to the research and development of novel immunologic drugs and their application in treating malignant tumors. However, few immunologic drugs can be administered to treat Small Cell Lung Cancer (SCLC). Currently, the focus of most clinical studies is placed on treating SCLC with a combination of immunotherapy and chemotherapy, which is relatively expensive and not covered by medical insurance, thus imposing a heavy economic burden on patients. Meanwhile, obvious adverse reactions occur during chemotherapy, which is still unacceptable to many patients and hence has not yet been widely adopted in clinical practice. Therefore, whether immunotherapy alone can help patients with SCLC, improve their quality of life, and prolong their survival time is a topic we will study in the future. In this case, an attempt was made to apply camrelizumab, an immunologic drug, in the treatment of SCLC in advanced stages, and a favorable efficacy was achieved.

Potential role of serum proteome in predicting immune-related adverse events from immune checkpoint inhibitors in non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21218-e21218
Author(s):  
Leeseul Kim ◽  
Young Kwang Chae ◽  
Chan Mi Jung ◽  
Emma Yu ◽  
Alice Daeun Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Nsclc Patients

e21218 Background: Early recognition of immune-related adverse events (irAEs) of immune checkpoint inhibitors(ICI) is important. Circulating proteome reflects host response to diseases and is being explored as a marker for response to immunotherapy. We previously have reported that a serum-based proteomics test, Primary Immune Response (PIR) demonstrated a trend that PIR-sensitive patients are more likely to tolerate ICI treatment longer without developing irAEs in non-small cell lung cancer (NSCLC) patients. The VeriStrat test is another serum-based proteomic assay, which was reported to be predictive of survival outcomes for all treatment regimens and lines of therapy including ICI in NSCLC. We explored the associations between the VeriStrat test and developing irAEs in NSCLC patients treated with ICI. Methods: Data of 70 consented NSCLC patients treated with any regimens and lines of therapy including ICI were collected. Samples were grouped into either VeriStrat ‘Good’(VS-G) or VeriStrat ‘Poor’(VS-P). We analyzed the durations from the immunotherapy initiation to each episode of irAE and each irAE above grade 2 using log-rank test. IrAEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Among the 70 patients, 18 patients (25%) experienced one or more irAEs. There was no significant difference in ‘Time to first irAE’ between VS-G and VS-P (p = 0.72, HR = 0.82, 95% CI = 0.29-2.32). Among 48 VS-G patients, 12(25%) had one or more irAE and 5(10%)had irAE graded over 2. Among 22 VS-P patients, 6(27%) had one or more irAE and 2(9%) had irAE graded over 2. There was no significant difference between VS-G and VS-P groups in the development of irAE and irAE graded over 2. Conclusions: There was no statistically significant association between the VeriStrat test and the development of irAEs. Further studies are warranted to investigate proper serum based proteomic assay to predict the development of irAE.

Gastrointestinal Adverse Events Induced by Immune-Checkpoint Inhibitors

Digestion ◽  
2021 ◽  
pp. 1-9
Author(s):  
Shunichi Yanai ◽  
Yosuke Toya ◽  
Tamotsu Sugai ◽  
Takayuki Matsumoto
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Architectural Distortion ◽  
Management Guidelines ◽  
Crypt Abscess ◽  
Gastrointestinal Adverse Events ◽  
Histopathologic Findings

<b><i>Background:</i></b> As immune-checkpoint inhibitors (ICI) are becoming standard therapies for malignant tumors, increasing attention has been paid to their associated immune-related adverse events (irAEs). The gastrointestinal tract is the major site of irAEs, and it has recently become evident that the large bowel is the most frequently affected region. The aim of this narrative review was to clarify the endoscopic and histopathologic findings of and treatments for ICI-induced colitis. <b><i>Summary:</i></b> Endoscopic findings of ICI-induced colitis include a reddish, edematous mucosa with increased mucous exudate, loss of normal vascularity, and a granular mucosa with or without mucosal breaks. Histopathologic findings of ICI-induced colitis are expansion of the lamina propria, intraepithelial infiltration of neutrophils, crypt architectural distortion, neutrophilic crypt abscess, and prominent apoptosis. The clinical, endoscopic, and histopathologic severity of ICI-induced colitis is diverse, but colonoscopy together with biopsy is necessary for diagnosis. While a certain proportion of patients with ICI-induced colitis have an intractable clinical course, management guidelines are based on retrospective analyses. Prospective studies are needed to assess the efficacy of various medications, including immunosuppressive regimens. <b><i>Key Messages:</i></b> Colonoscopy with biopsy is the gold standard for the diagnosis of ICI-induced colitis. Endoscopists should be aware of the clinical features and pathophysiology of ICI-induced colitis for prompt diagnosis and treatment planning.

Panuveitis in patient on ipilimumab/nivolumab combination for small-cell lung cancer treated with an intravitreal dexamethasone implant

2020 ◽  
pp. 107815522096979
Author(s):  
Jade L Hefler ◽  
Lauren M Bailey ◽  
Cynthia El Rahi ◽  
Amy C Schefler ◽  
Eric H Bernicker
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Antitumor Effects ◽  
Serious Adverse Events

Background Immunotherapy with checkpoint inhibitors has demonstrated durable responses and remarkable antitumor effects in a variety of cancers. Although these agents are generally well-tolerated, patients can experience immune-related adverse events (irAEs) that require prompt recognition by healthcare providers. Immune-related ocular toxicities are rare, but serious adverse events have been reported with the use of checkpoint inhibitors. Case presentation: Here, we describe a rare case of panuveitis during Nivolumab and Ipilimumab combination treatment in a patient being treated for recurrent Small Cell Lung Cancer (SCLC). The patient was managed with an injection of Ozurdex (Allergan, Madison, NJ), a dexamethasone intravitreal implant. The patient had a resolution of inflammation and an improvement in her vision and was able to resume nivolumab monotherapy without recurrence of the panuveitis. Conclusion This case highlights the importance of early recognition of ocular irAEs by ocular oncologists and the successful approach to treatment of immunotherapy-induced panuveitis in order to avoid permanent cessation of therapy.

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