Checkpoint Inhibitor-related Pneumonitis Research Articles

Cellular analysis of bronchoalveolar lavage fluid to narrow differential diagnosis of checkpoint inhibitor-related pneumonitis in metastatic melanoma

BackgroundThe diagnosis of check-point inhibitor-related pneumonitis (CIP) relies on radiological and clinical patterns which are not specific and can mimic other conditions (cancer progression, infectious diseases or interstitial pneumonitis). Cell pattern analysis of bronchoalveolar lavage (BAL) is well-known to support the diagnosis of interstitial lung disease; nevertheless, this analysis is somewhat performed and not required by immune-toxicity management guidelines for CIP.MethodsWe performed BAL analysis in 5 metastatic melanoma (MM) patients who developed CIP among 112 patients treated with checkpoint inhibitors. We also correlated the BAL features with the computed tomography (CT) scan patterns and with various peripheral blood parameters to better define the profile of this patient population.ResultsBAL flow cytometer and cytopathology analyses showed typical and homogeneous features with increased lymphoid population, prevalent CD8 + T cells and inversion of the CD4/CD8 ratio. Moreover, the extent of activated CD3 + HLA-DR + T cells was related to the grading of adverse events. Blood leucocytosis, hypoxemia, normal values for procalcitonin and lactate dehydrogenase were also found together with a cryptogenic organizing pneumonia-like radiologic pattern. In all our patients, CIP was associated with partial or complete response.ConclusionsIdentification of a specific BAL cellular pattern allows clinicians to place this investigation in the appropriate position of CIP diagnosis and management to avoid misdiagnosis or considering this condition as progressive disease and delaying proper treatment.

Clinical characteristics and management of immune checkpoint inhibitor-related pneumonitis: A single-institution retrospective study.

IntroductionThe increasing application of immune checkpoint inhibitors (ICIs) will cause more checkpoint inhibitor‐related pneumonitis (CIP), which is a common cause of ICI‐related death. The clinical management of CIP needs further optimization.MethodsPatients who were managed at Peking Union Medical College Hospital (PUMCH) between February 2017 and December 2019 with a diagnosis of CIP were retrospectively analyzed. Clinical data including clinical manifestations, radiologic data, laboratory and bronchoscopy results, treatments, and outcomes were collected and analyzed. The Mann–Whitney test was used to compare patients with and without co‐infections.ResultsIn total, 48 CIP cases in 42 patients were analyzed. The median time from the first dose of ICI to the onset of CIP was 1.9 months (range: 0.1–13.7). Grade 3–4 (G3–4) accounted for 30 cases (71.4%). The most common symptoms were cough (88.1%) and dyspnea (78.6%). The median starting dose of equivalent prednisone (EP) was 55 mg (range: 30–200) for all patients. The median total duration of glucocorticosteroids (GCS) treatment was 42.5 days (range: 15−89). Three patients (7.14%) died because of infection. A higher starting dose and longer duration of GCS (≥30 mg/day; p = 0.001) were associated with opportunistic infection. Chest computed tomography (CT) showed diverse and asymmetrical lesions. Twelve patients were re‐challenged, and six patients developed recurrent CIP.ConclusionsThe clinical and imaging manifestations of CIP are various, and differential diagnosis of exclusion is essential. GCS at 1–2 mg/kg is feasible to treat CIP, but the duration of GCS ≥30 mg/day should be used with caution, given the high risk of acquired infections. Re‐challenges of ICI are feasible, but the recurrence of CIP needs to be closely monitored.

SINGLE-DOSE DURVALUMAB INDUCED SARCOIDOSIS-LIKE REACTION WITH GRANULOMA IN NON-SMALL CELL LUNG CANCER

SESSION TITLE: Medical Student/Resident Lung Cancer Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: PD-1 inhibitors are revolutionizing the way oncology is practiced in a variety of cancer types. While there are fewer, side effects than chemotherapy, they are not without immune-related adverse events (irAE). These adverse events can affect organ systems such as the GI tract, liver, nervous system and lungs. Pneumonitis is an uncommon iRAE, with about a 3.6% incidence. The differential for pneumonitis includes organizing pneumonia, mycoplasma, radiation therapy, and ICI use. Multiple etiologies can produce clinical and radiological similarities with features similar to pneumonitis such as organizing pneumonia, radiation, and sarcoid-like reaction (SLR). SLR, like pneumonitis, is treated with steroids. In most cases symptoms resolve and ICI use can resume. Biopsy and bronchoscopy are not indicated unless the underlying cause cannot be identified. As evidenced in our case, changes on imaging in patients with ICI's need to be monitored and treated appropriately. CASE PRESENTATION: We present the case of a 60-year-old female with stage IIIb T3N2M0, histologic grade 3, EGFR and ALK/ROS negative NSCLC that received one dose of Durvalumab and developed pneumonitis with underlying SLR 15 days after initiation. She received 4 cycles of Carboplatin/Pemetrexed with concurrent radiation followed by Durvalumab. There was a significant reduction in tumor size from her initial PET/CT scan in terms of her cancer. Epithelioid granulomas were found on biopsy 15 days after Durvalumab initiation. She then developed respiratory failure with subsequent expiration. DISCUSSION: To our knowledge, this is the first reported case of Durvalumab induced SLR after one cycle. In a majority of similar cases, patients' status did not deteriorate as rapidly and dramatically. Image changes with ICI’s raise suspicion for pneumonitis. The effects of prior radiation leading to SLR warrant investigation, and may have contributed. Diagnosis was complicated by bilateral ground glass appearance seen with pneumonitis, contrasted with SLR typically manifesting with focal consolidations. Etiologies such infection, underlying ILD and malignancy should be ruled out. Non-caseating granulomas are a hallmark of sarcoidosis. TH17 cells have been implicated in promotion of cellular recruitment and sustained inflammation in granulomas, whereas Tregs have anti-inflammatory properties. ICI’s promote increased Treg attenuation to allow the host immune system to recognize malignant cells. This in turn relegates Th17 cells to induce pro inflammatory states seen in granuloma formation. We surmise ICI use creates a microenvironment conducive to granuloma formation by disrupting this Th17 vs Treg equilibrium. CONCLUSIONS: High suspicion needs to be taken when patients on ICI’s when there are changes on imaging. Although bronchoscopy and biopsy are not indicated, clinical judgment needs to be exercised to determine possible underlying etiologies. Reference #1: Anderson R, Theron AJ, Rapoport BL. Immunopathogenesis of Immune Checkpoint Inhibitor-Related Adverse Events: Roles of the Intestinal Microbiome and Th17 Cells. Frontiers in Immunology. 2019;10. doi:10.3389/fimmu.2019.02254 Reference #2: Cho JY, Kim J, Lee JS, et al. Characteristics, incidence, and risk factors of immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer. Lung Cancer. 2018;125:150-156. doi:10.1016/j.lungcan.2018.09.015 Reference #3: Khunger, M., Rakshit, S., Pasupuleti, V., Hernandez, A. V., Mazzone, P., Stevenson, J., … Velcheti, V. (2017). Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer. Chest, 152(2), 271–281. doi: 10.1016/j.chest.2017.04.177 DISCLOSURES: No relevant relationships by raman desikan, source=Web Response no disclosure on file for Krishna Kakkera; No relevant relationships by Philip Sobash, source=Web Response

Risk of Developing Checkpoint Immune Pneumonitis and Its Effect on Overall Survival in Non-small Cell Lung Cancer Patients Previously Treated With Radiotherapy.

IntroductionImmune checkpoint inhibitor-related pneumonitis (ICIP) is a potentially life threatening immune-related adverse event (irAE), especially in non-small cell lung cancer (NSCLC) patients. Currently, the potential for increased irAE in patients who receive radiotherapy is scarcely known, although a connection between antitumor immune responses and irAEs has been suggested. In this study, we evaluated the development of ICIP in non-small cell lung cancer patients with prior radiotherapy, treated with immunotherapy in the second-line.MethodsIn this retrospective trial, we included patients treated with second-line immunotherapy at the National Cancer Institute in Mexico City from February 2015 to February 2018. Clinical, radiological and treatment variables were evaluated according to the presence of ICIP as defined by the Common Terminology Criteria for Adverse Events (4.0) in patients with or without a previous (≥months) history of radiotherapy.ResultsAmong 101 NSCLC patients who received treatment with ICIs, 22 patients (21.8%) were diagnosed with ICIP, of which 73% (16/22) had a history of radiotherapy (OR 6.04, 95% CI 2.03−18.0, p < 0.001). Median progression free survival and overall survival were similar in patients who developed ICIP compared with those who did not, however, patients who presented grade ≥ 2 ICIP had an increased risk of mortality (HR 2.54, 95% CI 1.20−5.34, p = 0.014).ConclusionIn this real-world cohort of NSCLC patients treated with ICI, the history of prior radiotherapy was associated with increased risk for ICIP development. Unlike other irAEs, grade ≥ 2 ICIP is an independent prognostic factor for decreased survival in NSCLC patients.

Association of baseline peripheral-blood eosinophil count with immune checkpoint inhibitor-related pneumonitis and clinical outcomes in patients with non-small cell lung cancer receiving immune checkpoint inhibitors

ObjectivesImmune checkpoint inhibitors (ICIs) have revolutionized the oncologic treatment landscape, but have been accompanied by immune-related adverse events (irAEs). ICI-related pneumonitis (ICI-pneumonitis) is a potentially fatal irAE. However, the risk factors associated with ICI-pneumonitis remain unclear. There is an urgent need to identify risk factors for ICI-pneumonitis using reliable and accessible parameters. Here, we aimed to identify baseline peripheral-blood biomarkers correlated with ICI-pneumonitis and clinical outcomes in patients with advanced non-small cell lung cancer (NSCLC) who were treated with ICIs. Materials and MethodsWe conducted a retrospective analysis of eligible patients with advanced NSCLC who were treated with ICIs at our center. Receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value for analyzing risk of ICI-pneumonitis. Multivariate logistic analysis was performed to identify risk factors of ICI-pneumonitis. Clinical characteristics and treatment outcomes were collected and compared according to the optimal cutoff value. ResultsA total of 300 patients were included, in which 54 patients (18 %) experienced ICI-pneumonitis. Patients with ICI-pneumonitis had a high level of baseline peripheral-blood absolute eosinophil count (AEC) than those without ICI-pneumonitis (P = 0.013). The optimal threshold of baseline peripheral-blood AEC to predict ICI-pneumonitis was 0.125 × 109 cells/L. The incidence of ICI-pneumonitis was higher in the high-AEC group (AEC ≥ 0.125 × 109 cells/L; 27.7 %) than in the low-AEC group (AEC < 0.125 × 109 cells/L; 9.8 %, P < 0.001). Moreover, patients with high AEC (compared with those with low AEC) had a higher objective response rate (ORR) (40.9 % versus 28.8 %, P = 0.029) and longer median progression-free survival (PFS) (8.93 months versus 5.87 months, P = 0.038). ConclusionsAmong patients treated with ICIs, a baseline feature of high AEC (≥0.125 × 109 cells/L) was associated with an increasing risk of ICI-pneumonitis, and with a better clinical outcome.

Clinical and radiological features of immune checkpoint inhibitor-related pneumonitis in lung cancer and non-lung cancers.

To investigate the clinical and radiological features of immune checkpoint inhibitor-related pneumonitis (ICI-P), a rare but serious pulmonary complication of cancer immunotherapy and to evaluate key differences between lung cancer (LC) and non-LC patients. 247 patients (LC, n = 151) treated with ICI for malignancies were retrospectively screened in a single institute. The number of patients, history of other immune-related adverse events (irAE), the onset, serum KL-6 levels, and chest CT features (types of pneumonitis, symmetry, laterality, location) were recorded for the ICI-P population and compared for LC and non-LC groups. ICI-P was identified in 26 patients in total (LC, n = 19; non-LC, n = 7). The incidence of other irAE was significantly higher in ICI-P group (63%) compared with patients without ICI-P (34%) (p = 0.0056). An earlier onset of ICI-P was recorded in LC (78 days) compared to non-LC patients (186 days) (p = 0.0034). Serum KL-6 was significantly elevated only in the non-LC group when ICI-P was noticed (p = 0.029). Major CT findings of ICI-P, irrespective of primary disease, were organizing pneumonia pattern and ground glass opacities. LC patients commonly exhibited consolidation and traction bronchiectasis and were prone to asymmetrical shadows (p < 0.001). Non-LC patients were more likely to exhibit symmetrical infiltrations. A small fraction of both groups experienced relapse or moving patterns of ICI-P. ICI-P patients more often experienced other irAE prior to the development of ICI-P. The characteristics of ICI-P can differ in terms of the onset, KL-6 reliability, and chest CT findings between LC and non-LC patients. In ICI-P patients, a history of other irAE can be more frequently observed. Differences in disease onset and radiological patterns between LC and non-LC patients might be helpful to make a diagnosis of ICI-P; however, longitudinal observation of chest CT scans is advised to observe the pneumonitis activity irrespective of cancer types.

Cytomegalovirus infection as an underestimated trigger for checkpoint inhibitor-related pneumonitis in lung cancer: a retrospective study.

Checkpoint inhibitor-related pneumonitis (CIP) is a rare but potentially fatal complication of immune checkpoint inhibitors (ICIs). At present, the mechanism of CIP is not completely clear. Cytomegalovirus (CMV) infection is widespread in the population. Chemotherapy and radiotherapy can lead to the reactivation of CMV. We aimed to investigate the association between CMV infection and CIP. We retrospectively identified all lung cancer patients treated with ICIs at our institute from January 2016 to May 2020. The association between the development of CIP and CMV infection status was analyzed. Among 251 cases analyzed, 29 (11.6%) patients with CIP were identified, of whom 12 (4.78%) cases had grade 3-4 CIP. All 12 patients with grade 3-4 pneumonitis were CMV-IgG-positive, indicating a previous CMV infection. Except for one CMV-DNA-positive patient, the other patients were CMV-DNA-negative. All but one patient was CMV pp65 antigen-positive, indicating an early reactivation of the virus. The histological features of CMV pneumonia were not found in all available lung tissues, including lung transplantation pathology in one patient and lung biopsies in three patients. Except for one patient who received delayed antiviral therapy, the symptoms improved after glucocorticoid combined with antiviral therapy. The use of ICIs can restore the immune function and cause an immune response to CMV antigen while the infection is still latent. Our study suggests that CIP may be an immune reconstitution syndrome associated with CMV infection. CMV infection may represent a potentially important trigger for CIP. Patients with severe CIP should be vigilant against CMV infection. The early use of glucocorticoid combined with antiviral therapy is pivotal to good prognosis.

IBS13.01 Radiation Related Toxicities in Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC)

Radical radiotherapy is used as definitive therapy in locally advanced non-small cell lung cancer (LA-NSCLC), either alone or in combination with chemotherapy and/or surgery. However, definitive doses of radiotherapy are associated with potential toxicity related to the organs at risk (OAR). The major OAR’s related to radical radiotherapy for LA-NSCLC include the lung and esophagus. Therefore, we need to be able to identify and manage radiation pneumonitis and esophagitis during and after a course of definitive radiotherapy. For good performance status, unresectable stage III NSCLC, radical radiotherapy is delivered either concurrently or sequentially with chemotherapy to total doses of 60Gy or higher. Although the best outcomes have been obtained with concurrent chemoradiotherapy, higher rates of toxicity have also been observed. With the advent of the establishment of adjuvant durvalumab after definitive concurrent chemoradiotherapy, the management of pneumonitis in particular has become even more of a challenge given the potential overlapping toxicities. For poorer performance status patients, radical radiotherapy may be used alone. For resectable patients with LA-NSCLC, radical radiotherapy can be given concurrently with chemotherapy prior to surgical resection as part of trimodality therapy. In other instances, radical radiotherapy can be given adjuvantly post-operatively for positive margins and can be considered in pathological N2 disease. Prophylactic Cranial Irradiation (PCI) has also been delivered in LA-NSCLC, although mostly in clinical trials as PCI has not been established as part of routine standard of care in stage III NSCLC. In this session, a discussion as well as case presentations will be used to illustrate how to identify and manage the above toxicities in stage III NSCLC. References (max 10) Baker S, Fairchild A. Radiation-induced esophagitis in lung cancer. Lung Cancer: Targets and Therapy 2016:7 119–127. (Review Article). Mehmood Q, Sun A, Becker N, et al. Predicting Radiation Esophagitis Using 18F-FDG PET During Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. 2016: 1;11(2):213-21. Verma V, Simone CB, Werner-Wasik M. Acute and Late Toxicities of Concurrent Chemoradiotherapy for Locally-Advanced Non-Small Cell Lung Cancer. Cancers. 2017; 9:120. (Review Article). Jain V and Berman AT. Radiation Pneumonitis: Old Problem, New Tricks. Cancers (Basel). 2018 Jul 3; 10(7). (Review Article). Antonia SJ, Villegas A, Daniel D, et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. N Engl J Med 2018; 2018 Sep 25. Shaverdian, N, Lisberg AE, Bornazyan, K et al. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: A secondary analysis of the KEYNOTE-001 phase I trial. Lancet Oncol. 2017, 18(7), 895–903. Chuzi S, Tavora F, Cruz M, et al. Clinical features, diagnostic challenges, and management strategies in checkpoint inhibitor related pneumonitis. Cancer Manag Res. 2017;9:207-213. (Review Article). Sun A, Bae K, Gore EM, et al. Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer: neurocognitive and quality-of-life analysis. J Clin Oncol 2011; 29: 279–86. Le Pechoux C, Sun A, Slotman BJ, et al. Prophylactic cranial irradiation for patients with lung cancer. Lancet Oncol 2016; 17(7): e277–293. (Review Article). Sun A, Hu C, Wong SJ, et al. Prophylactic Cranial Irradiation vs Observation in Patients With Locally Advanced Non-Small Cell Lung Cancer: A Long-term Update of the NRG Oncology/RTOG 0214 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2019 Mar 14. Radiation Toxicity LA-NSCLC

Toxicités pulmonaires des immunothérapies : évaluer et traiter

Immune checkpoint inhibitor-related pneumonitis (ICI-P) during cancer treatment is rarely observed (<5%). ICI-Ps are more often observed in patients with non-small-cell lung cancer (NSCLC) than in those with other cancers. Likewise, they are more common in those receiving programmed cell death 1 (PD-1)/PD-ligand L1 (PD-L1) inhibitors rather than cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors alone. The frequency of ICI-P is higher when anti-PD1 and anti-CTLA-4 are administered concomitantly. Despite their low fatality rate (≈ 13%), ICI-Ps are the leading cause of ICI-related deaths. This narrative review focuses on the epidemiology, clinical and radiological presentation, and prognosis of ICI-P occurring in patients, especially those with advanced NSCLC. Emphasis is placed on the differences in terms of frequency or clinical picture observed depending on whether the ICI is used as monotherapy or in combination with another ICI or chemotherapy (CT). Other pulmonary complications observed in cancer patients, yet not necessarily immune-related, are reviewed, such as sarcoid-like granulomatosis, tuberculosis, or other infections. A proposal for pragmatic management, including differential diagnosis and therapeutic strategies, is presented, based on the ICI-P series reported in the literature and published guidelines.© 2019 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Clinical and Histopathologic Features of Immune Checkpoint Inhibitor-related Pneumonitis.

Immune checkpoint inhibitors (ICIs) have revolutionized oncology, but are associated with immune-related adverse events. Clinically, pneumonitis is a well-recognized complication, but its histopathologic features are poorly understood. Institutional archives were searched for patients having ICI therapy and subsequent lung tissue sampling. After excluding infectious cases, 9 patients (5 women, median: 59 y) were identified with clinically suspected ICI-related pneumonitis. Clinical history, imaging, and pathology slides were reviewed. Patients received pembrolizumab (6 cases), nivolumab (1), ipilimumab followed by pembrolizumab (1), or pembrolizumab followed by nivolumab (1); the latter experienced pneumonitis with both agents. Treatment duration ranged from 1 to 33 cycles (median: 8). Three patients received concurrent chemotherapy and 1 received radiation; the remainder received ICI monotherapy. Symptoms were nonspecific; 2 patients were asymptomatic. Thoracic imaging showed bilateral ground glass or nodular opacities in all cases, often with pleural effusion. Histologically, organizing pneumonia was seen in 7 patients, all with subclinical or mild disease, admixed with vague non-necrotizing airspace granulomas in 3 cases; all 6 patients with follow-up did well. One patient had acute fibrinous pneumonitis and 1 had diffuse alveolar damage; both died. All 9 cases showed foamy macrophages and pneumocyte vacuolization; 6 had rare eosinophils. ICI-related pneumonitis presents as bilateral ground-glass opacities or nodules, and usually manifests as organizing pneumonia histopathologically, often with vague non-necrotizing airspace granulomas. Foamy macrophages and pneumocyte vacuolization are characteristic and rare eosinophils are often seen. Less commonly, acute fibrinous pneumonitis or diffuse alveolar damage can occur, which may be fatal.

Pulmonary complications of immune checkpoint inhibitors in patients with nonsmall cell lung cancer.

Immune checkpoint inhibitor-related pneumonitis (ICI-P) during cancer treatment is rarely observed (<5%). ICI-P is more often observed in patients with nonsmall cell lung cancer (NSCLC) than in those with other cancers. Likewise, it is more common in those receiving programmed cell death (PD)-1/PD-1 ligand inhibitors rather than cytotoxic T-lymphocyte antigen (CTLA)-4 inhibitors alone. The frequency of ICI-P is higher when anti-PD-1 and anti-CTLA-4 are administered concomitantly. Despite the low fatality rate (≈13%), ICI-P is the leading cause of ICI-related deaths. This narrative review focuses on the epidemiology, clinical and radiological presentation and prognosis of ICI-P occurring in patients, especially those with advanced NSCLC. Emphasis is placed on the differences in terms of frequency or clinical picture observed depending on whether the ICI is used as monotherapy or in combination with another ICI or chemotherapy. Other pulmonary complications observed in cancer patients, yet not necessarily immune-related, are reviewed, such as sarcoid-like granulomatosis, tuberculosis or other infections. A proposal for pragmatic management, including differential diagnosis and therapeutic strategies, is presented, based on the ICI-P series reported in the literature and published guidelines.

A CHECK POINT INHIBITOR-RELATED FATAL TOXICITY

SESSION TITLE: Medical Student/Resident Lung Pathology 3 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Monoclonal antibodies against the immune checkpoint programmed cell death receptor 1 (PD-1) improve the hosts antitumor immune response and have demonstrated tremendous promise in the treatment of certain malignancies. Recently, there are emerging reports of serious autoimmune related toxicities from immune checkpoint blockade therapy. In our practice, we have encountered a fatal immune related adverse event on a patient who was treated with pembrolizumab. CASE PRESENTATION: 74 year old male with biopsy proven stage IV squamous cell esophageal cancer with metastasis to the lung presented to our service with a upper respiratory infection and cough with rusty colored sputum. He had been treated with pembrolizumab 3 days prior to the patient’s presentation. On examination, the patient was found to be hypoxemic on room air, tachycardic, and tachypneic. Initial chest film showed diffuse interstitial infiltrates; CT angiography of the chest elucidated significant new diffuse ground-glass infiltrates. The patient was initially treated for a suspected acute infectious pneumonia requiring high levels of noninvasive oxygen supplementation. Due to the lack of other etiologies such as environmental, infectious, and occupational, it was determined by pulmonology that this was most likely an adverse effect of the patient’s immunotherapy. The imaging studies were similar to previously seen pembrolizumab induced auto-immune pneumonitis. In accordance with both the pulmonology and oncology services, the patient was treated with high dose systemic steroids. Despite this, the dyspnea worsened and the patient declined mechanical ventilation. Eventually, he succumbed to the sequelae of pembrolizumab related auto-immune grade IV pneumonitis causing respiratory failure and cardiac arrest. DISCUSSION: The overall use of check-point inhibitors (CPIs) has increased survival in patients with certain types of cancer. While serious toxicities have been described in the literature from CPI therapy there are limited case reports describing auto-immune adverse effects such as vitilgo, auto-immune encephalitis, and auto-immune pneumonitis. In our review of previous literature, we found that there have only been several reported cases of auto-immune pneumonitis. In our case, there was a direct correlation between pembrolizumab and the development of grade IV auto-immune pneumonitis causing acute respiratory failure and death. CONCLUSIONS: There is a known relationship in the development of autoimmune toxicities in patients receiving checkpoint inhibitors. Clinicians need to have a high index of suspicion for high grade intestinal pneumonitis when patients treated with CPIs present with respiratory symptoms. It behooves us to further educate ourselves and direct therapy accordingly. These results encourage future Randomized Controlled trials (RCTs) to follow the efficacy and long-term side effects of these new therapies. Reference #1: Nishino, M. (2016). Incidence of Programmed Cell Death 1 Inhibitor-Related Pneumonitis in Patients With Advanced Cancer: A Systematic Review and Meta-analysis. JAMA Oncology, 12. doi:10.1001 Reference #2: Nishino, M. (2016). PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course. Clinical Cancer Research, 24. doi:10.1158 Reference #3: Chuzi, S. (2017). Clinical features, diagnostic challenges, and management strategies in checkpoint inhibitor-related pneumonitis. Cancer Management Research, 9. doi:10.2147 DISCLOSURES: No relevant relationships by Nemer Dabage, source=Web Response No relevant relationships by Ian Kahane, source=Web Response No relevant relationships by fiorella pendola, source=Web Response No relevant relationships by Vijay Srinivasan, source=Web Response

Characteristics, incidence, and risk factors of immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer

ObjectivesImmune checkpoint inhibitors (ICIs) can cause pneumonitis in lung cancer patients. We aimed to identify the clinical and radiologic characteristics, incidence, and risk factors of ICI-related pneumonitis in patients with non-small cell lung cancer (NSCLC). Materials and MethodsMedical records and chest computed tomography scans of NSCLC patients treated with an ICI over a 5-year period at a tertiary hospital were retrospectively analyzed. Clinical characteristics were compared between patients with and without ICI-related pneumonitis to identify risk factors. ResultsData from 167 eligible patients were analyzed. The incidences of all-grade and grade 3–4 pneumonitis were 13.2% and 4.2%, respectively. The presence of preexisting interstitial lung disease [odd ratio (OR), 6.03; 95% confidence interval (CI), 1.19–30.45; P = 0.030] was associated with a higher incidence of ICI-related pneumonitis. The presence of extrathoracic metastasis [OR, 0.34; 95% CI, 0.13–0.92; P = 0.034] was associated with a lower incidence of ICI-related pneumonitis. The dominant radiologic pattern (72.7%) of ICI-related pneumonitis was organizing pneumonia. Half of the patients with pneumonitis completely recovered or improved; however, the mortality rate was 18.2%. ConclusionICIs should be used with caution when treating lung cancer patients who have underlying chronic lung disease, especially interstitial lung disease.

Clinical features, diagnostic challenges, and management strategies in checkpoint inhibitor-related pneumonitis

Immune checkpoint inhibitors, including cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) inhibitors, represent an effective treatment modality for multiple malignancies. Despite the exciting clinical benefits, checkpoint inhibition is associated with a series of immune-related adverse events (irAEs), many of which can be life-threatening and result in significant treatment delays. Pneumonitis is an adverse event of special interest as it led to treatment-related deaths in early clinical trials. This review summarizes the incidence of pneumonitis during treatment with the different checkpoint inhibitors and discusses the prognostic significance of tumor type. The wide range of clinical, radiographic, and histologic characteristics of checkpoint inhibitor-related pneumonitis is reviewed and followed by guidance on the different management strategies.