Immune checkpoint inhibitors (ICIs) are first line treatment for advanced lung cancer. Tobacco use is a shared risk factor for lung cancer and chronic obstructive pulmonary disease (COPD). Although many patients with COPD and lung cancer receive ICIs, the impact of ICIs on COPD is unknown. Here, we evaluated whether ICI treatment was associated with increased COPD disease burden. We conducted a retrospective cohort study of lung cancer patients with and without preexisting COPD who received ICIs from 2011-2021 at The Ohio State University (OSU). For all patients, number of steroid courses and respiratory related hospitalizations were recorded. For those with COPD, COPD medications were collected at and after ICI initiation. Pulmonary function tests, COPD exacerbations, and COPD-related hospitalizations were compared before and after ICI treatment. Linear and generalized mixed models were used to account for potential confounders of worsening COPD. Among 1083 lung cancer patients who received ICIs, 585 (54.0%) had pre-ICI COPD. Patients with COPD were prescribed more COPD medications (3 [1, 4] vs 1 [0, 3], p < 0.001), had more COPD exacerbations (38.3% vs 25.8%, p < 0.001), and more COPD-related hospitalizations (27.9% vs 16.9%, p < 0.001) after ICI initiation compared to before. These findings persisted after multivariable analysis controlling for patients who received chemotherapy or chemoradiation within 12 months of ICI initiation, cancer type, age, BMI, sex, smoking status, type of ICI, and number of ICI doses (p < 0.001). This is a comprehensive study that describes lung cancer patients with COPD treated with ICIs have increased COPD disease burden after ICI initiation.

BACKGROUND:Immune checkpoint inhibitors (ICIs) have revolutionized cancer care with incredible reductions in mortality. One of the most devastating complications of treatment is ICI-related pneumonitis (ICI-p). Despite this, little is known regarding risk factors for severe pneumonitis and treatment effectiveness of various therapeutic options for steroid-refractory disease. To address this, we conducted a retrospective study on patients with cancer who developed ICI-p. METHODS:We examined consecutive patients who received ICIs and developed ICI-p. Risk factors of interest for severe disease and steroid-refractory ICI-p, including pre-treatment pulmonary function tests (PFTs) and chest imaging, were compared between patients with severe (grades 3-5) and mild (grades 1-2) pneumonitis. The clinical and treatment courses for patients with steroid-refractory ICI-p were recorded. RESULTS:A total of 132 patients developed ICI-p, with 60 patients having mild and 72 with severe disease. We found that lower forced vital capacity percent predicted (66.24 vs 85.05, P = .05), lower total lung capacity percent predicted (85.23 vs 99.71, P = .13), and specific radiographic patterns on pre-treatment chest imaging were predictors of severe disease. Initial corticosteroid dose of less than 1 milligram per kilogram prednisone equivalent (P = .14) was correlated with partially steroid-responsive or steroid-refractory ICI-p. Ten patients had steroid refractory ICI-p, and those who received IVIG alone as the immune suppressant beyond corticosteroids had improved survival (P = 05). CONCLUSIONS:We are the first to identify pre-treatment PFTs and chest imaging abnormalities as risk factors for severe ICI-p. We also found that lower corticosteroid doses were associated with partially steroid-responsive and steroid-refractory ICI-p. Larger, prospective studies are needed to validate our results.

IntroductionSarcoid-like reactions (SLRs) to immune checkpoint inhibitors (ICIs) are a rare but increasingly recognized immune-related adverse event of which the clinical significance is unclear.MethodsWe conducted a retrospective cohort study at a tertiary academic center of consecutive patients who received at least one dose of ICI from 2013-2020. Patient characteristics, risk factors, and outcomes were compared between patients with and without SLR following ICI treatment.ResultsA total of 2963 cancer patients received at least 1 dose of ICI between 2013-2020, and 7 patients (0.24%) developed SLR. There were no significant demographic differences between patients with and without SLR following ICI. SLRs occurred in 5 of 451 (1.07%) melanoma patients and 2 of 840 (0.24%) non-small cell lung cancer patients. Two of the 7 patients had multi-organ SLR, and both were symptomatic requiring systemic corticosteroids and permanent ICI discontinuation, while single organ SLR patients did not require immune suppression. Development of SLR did not appear to have negative impact on cancer progression or overall survival; in fact, a trend towards improved progression-free and overall survival was observed (median time: 1363 days vs 127 days, p = 0.091; 1387 days vs 428.5 days, p= 0.19, respectively).ConclusionsSLRs are a known but understudied complication associated with ICI therapy. Multisystem SLR patients were more symptomatic and required ICI discontinuation and immune suppression. Larger studies are needed to fully evaluate the impact of SLR on cancer outcomes.

PURPOSE: Adaptive flow (AF) is a patient-comfort feature used in the volume control mode on some mechanical ventilators.When activated, AF allows for increased flow in response to detection of excessive patient demand, which is sensed by the decreased airway pressure in the circuit.Since flow is increased over a fixed inspiratory time, larger tidal volumes (Vts) may be delivered than the desired setting.This study sought to assess the impact of AF on the ability to achieve target Vt < 8 mL/kg.Here we present a preliminary analysis of that data. METHODS:We conducted a retrospective cohort study of medical intensive care unit patients receiving volume-targeted mechanical ventilation for at least 48 hours in the year before (2017)(2018) and the year after (2018-2019) system-wide implementation of a ventilator featuring AF.The primary outcome was the proportion of patients receiving an average Vt > 8 mL/kg of ideal body weight (IBW) during the first 48 hours of intubation.Secondary outcomes included the median exhaled Vt, the median difference between set and exhaled Vt, new incidence of acute respiratory distress syndrome (ARDS), need for refractory hypoxemia interventions, ICU and hospital mortality, ICU and hospital length-of-stay, and ventilator-free days. RESULTS:Of 2680 charts pulled, to date we have screened 1482 and included 235 patients, 131 in the control group and 104 in the AF group.At baseline, patients in the control group were more likely to have asthma, COPD, ARDS on presentation, and had higher sequential organ failure assessment scores.Despite no difference in set tidal volume between groups, patients in the AF group were more likely to receive an average Vt > 8 mL/kg (13.7% vs 6.4%; odds ratio 3.4, 95% confidence interval 1.7 -6.7; p ¼ 0.0003).The median IBW-adjusted Vt was 6.6 mL/kg (interquartile range (IQR) 6.3 -7.2) and 7.2 mL/kg (IQR 6.8 -8.3) for the control and AF groups respectively (p < 0.0001).The median difference between set and delivered Vt was +27.7 mL (or +0.44 mL/kg) in the control group and +59.6 mL (or +0.97 mL/kg) in the AF group (p < 0.0001).These differences remained significant after adjusting for baseline characteristics.Of the secondary outcomes evaluated, new incidence of ARDS, use of neuromuscular blockade, and use of inhaled pulmonary vasodilators were all higher in the control group, but none remained significant after adjustment for covariates on multivariate logistic regression. CONCLUSIONS:This small preliminary analysis of a large retrospective study shows that volume control ventilation featuring AF is associated with delivery of average Vts higher than is recommended for lung protective ventilation.To assess the impact on patient-oriented outcomes will require ongoing data collection and analysis.CLINICAL IMPLICATIONS: AF may improve patient comfort at the expense of using improper lung protective ventilation.A larger sample size will be needed to evaluate whether this translates into increased risk of ventilator-induced lung injury, particularly for patients with ARDS.

2658 Background: Immune checkpoint inhibitor (ICI) induced pneumonitis (ICIp) can be severe and even fatal, but risk factors for severe ICIp remain poorly characterized. In this abstract, we characterize ICIp and assess factors associated with severe disease. Methods: This is a retrospective study of consecutive patients who received ICI therapy and developed ICIp at the Ohio State University (2013-2020). Patients with ICIp were identified from a pharmacy database using ICD-10 codes followed by chart review to confirm diagnosis. ICIp was graded based on the CTCAE v5.0 criteria. Laboratory values were collected at the onset of ICIp. A thoracic radiologist reviewed chest imaging for pattern and severity. Survival probabilities were estimated with Kaplan-Meier curve and compared with log rank test. Results: Of 2963 patients who received ICI, we identified 119 patients (4%) with ICIp: 75 (63%) were males; 79 (66%) received PD-1 inhibitor monotherapy; and 71 (60%) had lung cancer. ICIp was severe (grade 1-2) in 69 patients (58%) and mild (grade 3-5) in 50 (42%). 74 patients (62%) were hospitalized. 63 patients (53%) needed oxygen supplementation. ICI therapy was held in all patients except one. ICI was rechallenged in 26 patients; 6 of them (23%) had recurrence of ICIp symptoms. All but 2 patients received steroids for the treatment of ICIp. 10 patients received non-steroidal medications (7 IVIG, 2 infliximab, 1 rituximab, 1 abatacept, 1 cyclophosphamide). Steroids were tapered in 6 patients of those who received non-steroidal medications. 3 of the patients who received IVIG had improvement of symptoms. Factors associated with severe ICIp. 21 patients (18%) died while hospitalized for ICIp are shown. Patients with severe ICIp had shorter overall survival than those with mild ICIp (P < 0.001). Conclusions: ICIp is a serious adverse event that limits ICI treatment and can lead to hospitalization and death. Factors associated with severe ICIp in our study include lower lymphocyte and eosinophil counts, lower albumin levels, finding of consolidation or bronchiectasis on imaging, and lower predicted FVC and TLC. Prospective studies are merited to validate our findings and to investigate the appropriate treatment of ICIp. [Table: see text]

SESSION TITLE: Late Breaking Diffuse Lung Disease PostersSESSION TYPE: Original Investigation PostersPRESENTED ON: 10/18/2022 01:30 pm - 02:30 pmPURPOSE: The purpose of this study is to determine the incidence of sarcoidosis in cancer patients following treatment with immune checkpoint inhibitors and assess whether checkpoint inhibitor related sarcoidosis has a protective effect on cancer recurrence.METHODS: We examined consecutive patients who received immune checkpoint inhibitor therapy (ICI) between 2013 and 2020 at a tertiary medical center in Columbus, Ohio. All cases were reviewed by board-certified pulmonologists on the study team and attribution of sarcoidosis was determined by the presence of non-necrotizing granulomas on tissue biopsy and the lack of an alternate diagnosis (cancer progression, infection). Patient demographics, cancer diagnosis, ICI agent, time from ICI therapy to diagnosis of sarcoid, relapse or progression of cancer after diagnosis of sarcoid were recorded.RESULTS: Between 2013 and 2020, 8 post-checkpoint inhibitor sarcoidosis cases were identified from a total of 2,964 patients. The incidence of sarcoidosis following initiation of ICI therapy was 0.27%. The average time from ICI therapy to diagnosis of sarcoid was 487 days (range 101-1335 days), while the average number of ICI infusions received was 26 (5-75 doses). Melanoma was the most common primary cancer for post-ICI sarcoidosis with 6 cases (incidence of 1.16%, 6/518). Lung cancer was the primary cancer for 2 cases (incidence of 0.19%, 2/1075). All eight patients had pulmonary involvement in their sarcoidosis, one had skin involvement, and one had liver/GI involvement. Four patients had progression of their cancer after starting ICI and three died. One patient who had progression on ICI did not have any further progression after diagnosis of sarcoid. None of the patients received sarcoid-directed treatment.CONCLUSIONS: We demonstrate here that the incidence of sarcoidosis following ICI therapy is greater than the general population, which suggests ICI increases risk for sarcoidosis. This increased incidence is especially pronounced in patients with a primary diagnosis of melanoma. However, the incidence of sarcoidosis in lung cancers may be underrepresented because new or progressive lymphadenopathy in these patients may be less likely to be re-biopsied.CLINICAL IMPLICATIONS: Sarcoidosis is an underrecognized side effect of ICI, though its clinical significance on cancer prognosis is not clear. Cancer patients on ICI with progressive lymphadenopathy may not be from disease progression, and biopsy should be considered to rule out a sarcoid-like response, especially in melanoma patients who appear to have a higher incidence of post-treatment sarcoidosis. Further investigation will be needed to determine 1). Effects of sarcoidosis on cancer recurrence in a larger cohort that underwent sarcoid-directed therapies and 2). Whether treatment of post-checkpoint inhibitor sarcoidosis impacts cancer recurrence.DISCLOSURES:Collaboration via BARDA grant funding relationship with Beckman Coulter, Inc. Please note: 9/19/2019-8/31/2014 by Elliott Crouser, value=Grant/Research SupportRemoved 06/06/2022 by Elliott CrouserGrant recipient relationship with aTyr Pharmaceutical Please note: 2020-2023 Added 06/06/2022 by Elliott Crouser, value=Grant/ResearchGrant recipient relationship with Xentria Pharmaceutical Please note: 2021-2023 Added 06/06/2022 by Elliott Crouser, value=Grant/Research SupportBoard Member relationship with Foundation for Sarcoidosis Research Please note: 2020-2023 Added 06/06/2022 by Elliott Crouser, value=No financial supportNo relevant relationships by Robert EasterlingNo relevant relationships by Kevin HoNo relevant relationships by Arindam Singha SESSION TITLE: Late Breaking Diffuse Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: The purpose of this study is to determine the incidence of sarcoidosis in cancer patients following treatment with immune checkpoint inhibitors and assess whether checkpoint inhibitor related sarcoidosis has a protective effect on cancer recurrence. METHODS: We examined consecutive patients who received immune checkpoint inhibitor therapy (ICI) between 2013 and 2020 at a tertiary medical center in Columbus, Ohio. All cases were reviewed by board-certified pulmonologists on the study team and attribution of sarcoidosis was determined by the presence of non-necrotizing granulomas on tissue biopsy and the lack of an alternate diagnosis (cancer progression, infection). Patient demographics, cancer diagnosis, ICI agent, time from ICI therapy to diagnosis of sarcoid, relapse or progression of cancer after diagnosis of sarcoid were recorded. RESULTS: Between 2013 and 2020, 8 post-checkpoint inhibitor sarcoidosis cases were identified from a total of 2,964 patients. The incidence of sarcoidosis following initiation of ICI therapy was 0.27%. The average time from ICI therapy to diagnosis of sarcoid was 487 days (range 101-1335 days), while the average number of ICI infusions received was 26 (5-75 doses). Melanoma was the most common primary cancer for post-ICI sarcoidosis with 6 cases (incidence of 1.16%, 6/518). Lung cancer was the primary cancer for 2 cases (incidence of 0.19%, 2/1075). All eight patients had pulmonary involvement in their sarcoidosis, one had skin involvement, and one had liver/GI involvement. Four patients had progression of their cancer after starting ICI and three died. One patient who had progression on ICI did not have any further progression after diagnosis of sarcoid. None of the patients received sarcoid-directed treatment. CONCLUSIONS: We demonstrate here that the incidence of sarcoidosis following ICI therapy is greater than the general population, which suggests ICI increases risk for sarcoidosis. This increased incidence is especially pronounced in patients with a primary diagnosis of melanoma. However, the incidence of sarcoidosis in lung cancers may be underrepresented because new or progressive lymphadenopathy in these patients may be less likely to be re-biopsied. CLINICAL IMPLICATIONS: Sarcoidosis is an underrecognized side effect of ICI, though its clinical significance on cancer prognosis is not clear. Cancer patients on ICI with progressive lymphadenopathy may not be from disease progression, and biopsy should be considered to rule out a sarcoid-like response, especially in melanoma patients who appear to have a higher incidence of post-treatment sarcoidosis. Further investigation will be needed to determine 1). Effects of sarcoidosis on cancer recurrence in a larger cohort that underwent sarcoid-directed therapies and 2). Whether treatment of post-checkpoint inhibitor sarcoidosis impacts cancer recurrence. DISCLOSURES: Collaboration via BARDA grant funding relationship with Beckman Coulter, Inc. Please note: 9/19/2019-8/31/2014 by Elliott Crouser, value=Grant/Research Support Removed 06/06/2022 by Elliott Crouser Grant recipient relationship with aTyr Pharmaceutical Please note: 2020-2023 Added 06/06/2022 by Elliott Crouser, value=Grant/Research Grant recipient relationship with Xentria Pharmaceutical Please note: 2021-2023 Added 06/06/2022 by Elliott Crouser, value=Grant/Research Support Board Member relationship with Foundation for Sarcoidosis Research Please note: 2020-2023 Added 06/06/2022 by Elliott Crouser, value=No financial support No relevant relationships by Robert Easterling No relevant relationships by Kevin Ho No relevant relationships by Arindam Singha