Pneumonitis In Patients Research Articles

389P - Risk factors of nivolumab-induced pneumonitis in patients with solid tumors

Background: Nivolumab is an anti-programmed death 1 (PD-1) monoclonal antibody, which has demonstrated antitumor efficacy in clinical trials of various malignant tumors. Pneumonitis is a common adverse event in patients treated with nivolumab. However, the difference of the frequency and severity of nivolumab-induced pneumonitis across different tumor types is not clear. Methods: We retrospectively reviewed 311 patients who were diagnosed as non-small cell lung cancer (NSCLC), head and neck cancer (HNC), or gastric cancer (GC), and treated with nivolumab at Aichi Cancer Center Hospital, Japan, between December, 2015 and April, 2018. Patients who underwent chest computed tomography (CT) right before starting of nivolumab and have not received chemotherapy after the last chest CT were included in the analysis. Patients who previously received thoracic radiotherapy were excluded from the analysis. Pulmonary fibrosis score (scores 0–5) on baseline chest CT was assessed by two independent radiologists. Results: 196 patients were included in the analysis, and 96 patients were NSCLC, 50 patients were HNC, and 50 patients were GC, respectively. Pulmonary fibrosis score ≥1 was found in 27.1% in NSCLC, 10.0% in HNC, and 12.0% in GC (p = 0.02). Twenty-two patients (11.2%) experienced nivolumab-induced pneumonitis, of which three (1.5%) were grade ≥3. The median onset time of pneumonitis after starting nivolumab was 61 days (range, 2–634 days). According to the analysis of tumor types, the rates of pneumonitis were 14.6% in NSCLC, 10.0% in HNC, and 6.0% in GC, respectively. There were no significant differences in the incidences of pneumonitis between three tumor types. Univariate and multivariate logistic regression analysis revealed that male and pulmonary fibrosis score ≥1 significantly increased the risk of developing nivolumab-induced pneumonitis. Conclusions: Pulmonary fibrosis was found more frequently in NSCLC than HNC and GC. Our results indicated that male and pulmonary fibrosis are the risk factors for nivolumab-induced pneumonitis. Legal entity responsible for the study: Toyoaki Hida. Funding: Has not received any funding. Disclosure: K. Muro: Research grants: Ono Pharmaceutical. T. Hida: Research grants: Ono Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Pfizer, Bristol-Meyers Squibb, MSD. All other authors have declared no conflicts of interest.

Predicting severe acute radiation pneumonitis in patients with non-small cell lung cancer receiving postoperative radiotherapy: Development and internal validation of a nomogram based on the clinical and dose–volume histogram parameters

Background and purposePostoperative radiotherapy (PORT) can potentially lead to radiation pneumonitis. We aim to develop a nomogram predicting the severe acute radiation pneumonitis (SARP, grade ≥3) in patients with non-small cell lung cancer (NSCLC) receiving PORT. Materials and methodsClinical and dose–volume histogram (DVH) factors were collected from 109 patients between 2006 and 2017. The endpoint was the development of SARP within 3 months after PORT. Logistic regression was used to evaluate the prognostic value of each factor in predicting SARP. Nomogram was generated based on multivariate regression coefficients. Area under the ROC curve (AUC), calibration curves, and decision curve analyses (DCA) were conducted to validate the model. ResultsUnivariate and multivariate analysis indicated that total lung mean dose (tlMD) (OR: 1.003, 95%CI: 1.001–1.006, p = 0.013), percentage of ipsilateral lung volume receiving ≥5 Gy (ilV5) (OR: 1.084, 95%CI: 1.020–1.151, p = 0.009), and concurrent chemoradiotherapy (CCRT) (OR: 4.091, 95%CI: 1.331–12.572, p = 0.014) were independent prognosticators of SARP and were included in the nomogram. ROC curves revealed the AUC of the nomogram was 0.842, which was much higher than any factor alone (tlMD: 0.769; ilV5: 0.744; CCRT: 0.661). Calibration curves showed favorable consistency between the predicted SARP and the actual observation. DCA showed satisfactory positive net benefits of the model among most of the threshold probabilities, indicating great clinical effect. ConclusionWe identified that the tlMD (>10.8 Gy), ilV5 (>64.9%), and CCRT could predict SARP among patients with NSCLC receiving PORT. Combining clinical and DVH parameters, a nomogram was first built and validated, showing its potential value in practice.

Pre-existing pulmonary fibrosis is a risk factor for anti-PD-1-related pneumonitis in patients with non-small cell lung cancer: A retrospective analysis

ObjectivesPneumonitis related to the use of anti-programmed death 1 (PD-1) antibodies is a common immune-related adverse event that can be life-threatening. However, the relationship between pulmonary fibrosis/emphysema and the incidence of anti-PD-1-related pneumonitis is unclear. Materials and methodsWe retrospectively reviewed data from 123 patients who were diagnosed with non-small-cell lung cancer and treated with anti-PD-1 antibodies (nivolumab or pembrolizumab) at the Aichi Cancer Center Hospital, Japan, between December 17, 2015, and November 30, 2017. Patients who previously received thoracic radiotherapy to the primary lesion, mediastinum, spinal, or rib metastases were excluded from the analysis. Fibrosis score (0–5) and emphysema score (0–4) on baseline chest computed tomography (CT) were determined by two diagnostic radiologists. ResultsEighteen patients (14.6%) experienced anti-PD-1-related pneumonitis, of which four (3.3%) were grade ≥3. The median onset time of pneumonitis after starting anti-PD-1 therapy was 60 days (range, 6–634 days). According to the analysis of fibrosis score, pneumonitis occurred in 13 (35.1%) of the 37 patients with a fibrosis score ≥1 and in 5 (5.8%) of 86 patients with a fibrosis score of 0. Univariate and multivariate logistic regression analysis revealed that fibrosis score ≥1 was the only risk factor for anti-PD-1-related pneumonitis (p = 0.0008). ConclusionOur results indicate that pre-existing pulmonary fibrosis significantly increases the risk of anti-PD-1-related pneumonitis. Further studies are needed to identify predictive factors of anti-PD-1-related pneumonitis in patients with fibrotic changes on CT findings.

MS19.01 Drug-Induced Pneumonitis with IO: How worried should we be for our Lung Cancer Patients

MS19.01 Drug-Induced Pneumonitis with IO: How worried should we be for our Lung Cancer Patients

P2.12-18 Interstitial Lung Abnormalities are a Risk Factor for Radiation Pneumonitis in Patients with Limited-Stage Small-Cell Lung Cancer

Previous studies reported that patients wth preexisting radiological interstitial lung abnormalities (ILAs) were more susceptible to developing radiation pneumonitis (RP) after thoracic radiation therapy (TRT). The present study aimed to evaluate the incidence and predictors of RP after TRT in patients with limited-stage small-cell lung cancer (LS-SCLC) with or without preexisting radiological ILAs. A total of 183 consecutive patients with LS-SCLC between January 2015 and December 2016, who were treated with thoracic intensity-modulated radiation therapy at our institution, were analyzed. The diagnosis of ILAs was reviewed by two experienced thoracic radiologists based on the pretreatment high-resolution computed tomography(CT) imaging, such as honeycombing, subpleural reticular opacities, ground-glass opacity, and traction bronchiectasis. Univariate and multivariate analyses were used to assess the correlation of clinical factors, preexisting radiological ILAs, and dose-volume histogram-based dosimetric parameters with RP. The correlation between the preexisting ILAs score on CT findings and the grade of RP was analyzed by Pearson Correlation. Twenty (10.9%) patients had preexisting radiological ILAs. The median follow-up time was 10.9 months. RP was observed in 75 (41.0%), 35 (19.1%), 11 (6.0%), and 0 (0%) patients with grades 1, 2, 3, and ≥4 RP, respectively. The incidence of ≥ grade 2 and 3 RP at 1 year was 26.3% and 6.2% in the entire cohort, respectively. Preexisting radiological ILAs were associated with an increased risk of ≥grade 2 RP (84.1% in ILAs + vs 18.7% in ILAs-, P＜0.001) and ≥ grade 3 RP (27.7% in ILAs + vs 3.8% in ILAs-, P ＜0.001) at 1 year. Preexisting radiological ILAs was a significant predictors of ≥grade 2 RP and ≥grade 3 RP in multivariate analysis (P ＜0.001, P = 0.004, respectively). Lower forced expiratory volume in 1 second was a significant predictor of ≥grade 2 RP in multivariate analysis (P = 0.043). The ratio of CD4 and CD8 cells has a tendency to predict ≥grade 3 RP in multivariate analysis (P = 0.053).There was a moderate correlation between the preexisting ILAs score on CT findings and the grade of RP (Pearson Correlation Coefficient = 0.364, P ＜0.001). Preexisting radiological ILAs is associated with an increased risk of ≥grade 2 RP and ≥grade 3 RP after TRT in patients with LS-SCLC.

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

1207P - PD-1 inhibitor-related pneumonitis in patients with minimal interstitial lung shadows before treatment

1207P - PD-1 inhibitor-related pneumonitis in patients with minimal interstitial lung shadows before treatment

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.

A microRNA‑125a variant, which affects its mature processing, increases the risk of radiation‑induced pneumonitis in patients with non‑small‑cell lung cancer.

The present study aimed to investigate the role of microRNA (miR)‑125a in the development of pneumonitis inpatients with non‑small‑cell lung cancer that received radiotherapy. In addition, the study aimed to determine how the miR‑125a affects its target, transforming growth factor β (TGFβ). Bioinformatics tools were used to identify a potential miR‑125a binding site in the 3'untranslated region of TGFβ, which was subsequently confirmed using a dual‑luciferase reporter system. In addition, tissue samples were collected from patients with lung cancer and genotyped as CC (n=36), CT (n=28) or TT (n=6). The expression levels of miR‑125a and TGFβ in these samples were determined, and CC genotype samples demonstrated upregulated miR‑125a expression, and downregulated TGFβ protein and mRNA expression compared with samples carrying the minor allele, T. To further investigate the association between the rs12976445 polymorphism and the risk of pneumonitis in patients with lung cancer that received radiotherapy, 534 lung cancer patients diagnosed with pneumonitis and 489lung cancer patients without pneumonitis were recruited. rs12976445 was shown to be significantly associated with the risk of pneumonitis. In conclusion, the rs12976445 polymorphism increased expression levels of TGFβ by decreasing the expression of miR‑125a, and therefore may be associated with the development of pneumonitis in patients with lung cancer that receive radiotherapy.

Clinical Management of Pneumonitis in Patients Receiving Anti–PD-1/PD-L1 Therapy

CASE STUDY A 48-year-old gentleman with metastatic melanoma currently receiving the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor, ipilimumab (Yervoy), and the programmed cell death protein 1 (PD-1) inhibitor, nivolumab (Opdivo), returned for evaluation prior to receiving cycle 2. The patient presented with new onset dyspnea and a non-productive cough over the past week, with a temperature of 100.6°F at home on one occasion. He was placed on observation for fever, cough, and shortness of breath. The patient had no previous history of lung disease and was a nonsmoker. Diminished breath sounds were noted on auscultation. However, the patient was without fever or chills, with a heart rate of 101 beats per minute and a blood pressure of 110/75 mm Hg. We obtained a computed tomography (CT) of his chest. The CT demonstrated diffuse ground-glass opacities in his bilateral lower lobes and some minor interstitial thickening of his right middle lobe, possibly suggestive of inflammation or cryptogenic organizing pneumonia. Based on his presentation and CT findings, the patient was initially treated empirically with antibiotics for suspected pneumonia vs. pneumonitis. During the first 12 hours in observation, the patient experienced increasing dyspnea and cough and was admitted to the hospital. Nebulizer treatments were administered with no improvement, so the patient was started on high-dose corticosteroids at 1 mg/kg, and pulmonary and infectious disease consults were ordered. After the administration of steroids, the patient's cough and breathing improved and he remained afebrile, eliciting a high suspicion for immune-related pneumonitis. The patient then underwent bronchoscopy to rule out other etiologies. Bronchoalveolar lavage was performed, which yielded no pathogenic organisms. The patient was placed on a 3-week course of a high-dose steroid taper, following which immunotherapy was reinstated. Within 4 days he again presented with similar symptoms, was restarted on high-dose steroids, and immunotherapy was permanently discontinued.

Oral administration of herbal medicines for radiation pneumonitis in lung cancer patients: A systematic review and meta-analysis.

BackgroundRadiation pneumonitis is a common and serious complication of radiotherapy. Many published randomized controlled studies (RCTs) reveal a growing trend of using herbal medicines as adjuvant therapy to prevent radiation pneumonitis; however, their efficacy and safety remain unexplored.ObjectiveThe aim of this systematic review is to evaluate the efficacy and safety of herbal medicines as adjunctive therapy for the prevention of radiation pneumonitis in patients with lung cancer who undergo radiotherapy.MethodsWe searched the following 11 databases: three English medical databases [MEDLINE (PubMed), EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL)], five Korean medical databases (Korean Studies Information, Research information Service System, KoreaMed, DBPIA, National Digital Science Library), and three Chinese medical databases [the China National Knowledge Database (CNKI), Journal Integration Platform (VIP), and WanFang Database]. The primary outcome was the incidence of radiation pneumonitis. The risk of bias was assessed using the Cochrane risk-of-bias tool.ResultsTwenty-two RCTs involving 1819 participants were included. The methodological quality was poor for most of the studies. Meta-analysis showed that herbal medicines combined with radiotherapy significantly reduced the incidence of radiation pneumonitis (n = 1819; RR 0.53, 95% CI 0.45–0.63, I2 = 8%) and the incidence of severe radiation pneumonitis (n = 903; RR 0.22, 95% CI 0.11–0.41, I2 = 0%). Combined therapy also improved the Karnofsky performance score (n = 420; WMD 4.62, 95% CI 1.05–8.18, I2 = 82%).ConclusionThere is some encouraging evidence that oral administration of herbal medicines combined with radiotherapy may benefit patients with lung cancer by preventing or minimizing radiation pneumonitis. However, due to the poor methodological quality of the identified studies, definitive conclusion could not be drawn. To confirm the merits of this approach, further rigorously designed large scale trials are warranted.

Risk factors for pneumonitis in patients treated with anti-programmed death-1 therapy: A case-control study.

Immune checkpoint blockade‐related pneumonitis is a rare but potentially life‐threatening adverse effect, but its risk factors are not completely understood. This case‐control study was conducted to identify pneumonitis risk factors in patients treated with anti‐PD1 monoclonal antibodies (mAbs), including all the patients who developed pneumonitis after anti‐PD‐1 mAbs treatment in the Cancer Center of the Chinese People's Liberation Army from September 2015 to September 2017. Two controls per case were matched according to a propensity‐score matching algorithm to account for confounding effects caused by individual baseline variables. Demographic and clinical information was obtained from medical records. In total, 55 cases and 110 controls were included in the study. No association was observed between smoking status or primary lung cancer and risk of pneumonitis. Significant risk factors for pneumonitis related to anti‐PD‐1 mAbs were prior thoracic radiotherapy, prior lung disease and combination therapy with odds ratios of 3.34 (1.51‐7.39), 2.86 (1.45‐5.64) and 2.73 (1.40‐5.31), respectively. The associations remained significant in the multivariable logistic regression model. The risk of pneumonitis induced by anti‐PD‐1 mAbs is associated with prior thoracic radiotherapy, prior lung disease, and combination therapy. Clinicians should monitor these features in patients receiving anti‐PD‐1 therapy to optimize clinical safety and efficacy.

Incidence of pneumonitis in patients with solid tumors treated with everolimus: A systematic review and meta- analysis of randomized controlled trials.

e22220Background: Aberrant signaling through the PI3K/AKT/mTOR signaling pathway has been implicated in the pathogenesis of multiple cancers. Everolimus (E), an mTOR inhibitor, has been employed in...

Preexisting radiological interstitial lung abnormalities are a risk factor for severe radiation pneumonitis in patients with small-cell lung cancer after thoracic radiation therapy

BackgroundPrevious studies reported that patients with preexisting radiological interstitial lung abnormalities (ILAs) were more susceptible to developing radiation pneumonitis (RP) after thoracic radiation therapy (TRT). The present study aimed to evaluate the incidence and predictors of RP after TRT in patients with small-cell lung cancer (SCLC) with or without preexisting radiological ILAs.MethodsA total of 95 consecutive patients with SCLC between January 2015 and December 2015, who were treated with thoracic intensity-modulated radiation therapy at Shanghai Pulmonary Hospital,Tongji University School of Medicine, were analyzed. The diagnosis of ILAs was reviewed by two experienced thoracic radiologists based on the pretreatment high-resolution computed tomography imaging, such as honeycombing, subpleural reticular opacities, ground-glass opacity, and traction bronchiectasis. Univariate and multivariate analyses were used to assess the correlation of clinical factors, preexisting radiological ILAs, and dose-volume histogram-based dosimetric parameters with RP.ResultsFifteen (15.8%) patients had preexisting radiological ILAs. The incidence of ≥ grade 2 and 3 RP at 1 year was 27.1% and 12.7% in the entire cohort, respectively. Preexisting radiological ILAs were associated with an increased risk of ≥grade 2 RP (50.0% in ILAs + vs 23.3% in ILAs−, P = 0.017) and ≥ grade 3 RP (35.8% in ILAs + vs 8.9% in ILAs−, P = 0.005) at 1 year. Preexisting radiological ILAs and smoking history (≥40 pack-years of smoking) were significant predictors of ≥grade 3 RP in multivariate analysis (P = 0.023 and 0.012, respectively).ConclusionsPreexisting radiological ILAs and smoking history (≥40 pack-years of smoking) are associated with an increased risk of ≥grade 3 RP after TRT in patients with SCLC.

Patient-reported lung symptoms as an early signal of impending radiation pneumonitis in patients with non-small cell lung cancer treated with chemoradiation: an observational study.

Clinician ratings of concurrent chemoradiation (CRT)-induced radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) are based on both imaging and patient-reported lung symptoms. We compared the value of patient-reported outcomes versus normal-lung uptake of 18F-fluoro-2-deoxyglucose in positron emission computed tomography (FDG PET/CT) during the last week of treatment, for indicating the development of grade ≥ 2 RP within 4 months of CRT completion. 132 patients with NSCLC-reported RP-related symptoms (coughing, shortness of breath) repeatedly using the validated MD Anderson Symptom Inventory lung cancer module. Of these patients, 68 had FDG PET/CT scans that were analyzed for normal-lung mean standardized FDG uptake values (SUVmean) before, during, and up to 4 months after CRT. Clinicians rated RP using CTCAE version 3. Logistic regression models examined potential predictors for developing CTCAE RP ≥ 2. For the entire sample, patient-rated RP-related symptoms during the last week of CRT correlated with clinically meaningful CTCAE RP ≥ 2 post-CRT (OR 2.74, 95% CI 1.25-5.99, P = 0.012), controlled for sex, age, mean lung radiation dose, comorbidity, and baseline symptoms. Moderate/severe patient-rated RP-related symptom score (≥ 4 on a 0-10 scale, P = 0.001) and normal-lung FDG uptake (SUVmean > 0.78, P = 0.002) in last week of CRT were equally strong predictors of post-CRT CTCAE RP ≥ 2 (C-index = 0.78, 0.77). During the last week of CRT, routine assessment of moderate-to-severe RP-related symptoms provides a simple way to identify patients with NSCLC who may be at risk for developing significant post-CRT RP, especially when PET/CT images of normal-lung FDG uptake are not available.

Risk factors for and characteristics of pneumonitis in patients treated with anti-programmed death-1 therapy.

128 Background: Pneumonitis is an uncommon but potentially fatal toxicity of anti–programmed death-1 (PD-1) monoclonal antibodies (mAbs), but its prevalence, risk factors and clinical features are poorly described. Methods: The medical records of 234 patients with advanced cancer who underwent anti–PD-1mAbs therapies between September 2015 and September 2017 at the Cancer Center of the Chinese PLA (People’s Liberation Army) General Hospital were analyzed with regard to patient background and clinical features. Pneumonitis was diagnosed by the treating investigator; cases with confirmed malignant lung infiltration or infection were excluded. Univariate and multivariate analyses were performed to identify independent predictive factors for pneumonitis. Clinical features, management and prognosis of pneumonitis were also collected. Results: A total of 55 patients (23.5%) developed pneumonitis. Anti–PD-1mAbs induced pneumonitis was significantly associated with male sex, a history of prior thoracic radiotherapy, combination therapy and underlying lung condition (odds ratios 3.380, 3.081, 2.538 and 2.559, respectively). Time to onset of pneumonitis ranged from 2 days to 277days (median time was 85days). 85.4% (47 of 55) of cases were grade 1 to 2, 25.5% (14 of 55) were treated with steroid therapy, of which 85.7% (12 of 14) resolved/ improved. Nine (16.4%) patients worsened clinically and one died during the course of pneumonitis treatment. Conclusions: Pneumonitis associated with anti–PD-1 mAbs is a serious adverse effect in the clinical setting that cannot be ignored. However, patient selection based on sex, history of prior thoracic radiotherapy, combination therapy and underlying lung condition can minimize pneumonitis risk. Most events are low grade and resolved/ improved with steroid therapy. Rarely, pneumonitis worsens despite steroid therapy, and may result in death.

Clarithromycin mitigates radiation pneumonitis in patients with lung cancer treated with stereotactic body radiotherapy.

Radiation pneumonitis is a critical pulmonary toxicity after irradiation of the lung. Macrolides including clarithromycin (CAM) are antibiotics. They also have immunomodulatory properties and are used to treat respiratory inflammatory diseases. Radiation pneumonitis has similar pathology to them. Adverse reactions to macrolides are few and self-limited. We thus administered CAM to patients with high-risk factors for radiation pneumonitis, and retrospectively investigated whether CAM mitigated radiation pneumonitis following stereotactic body radiotherapy (SBRT). Among consecutive patients treated with SBRT, we retrospectively examined lung cancer patients treated with a total dose of 40-60 Gy in 5-10 fractions and followed ≥6 months. Since January 2014, CAM has been administered in patients with pretreatment predictable radiation pneumonitis high-risk factors, including idiopathic interstitial pneumonias (IIPs), and elevated Krebs von den Lungen-6 (KL-6) and/or surfactant protein D (SP-D), and in patients developing early onset radiation pneumonitis. Five hundred and eighty eligible patients were identified and divided into 445 patients during the non-CAM-administration era (non-CAM-era) (before December 2013) and 136 patients during the CAM-administration era (CAM-era) (after January 2014). Median follow-up durations were 38.0 and 13.9 months, respectively. The rates of radiation pneumonitis ≥ grade 2 and ≥ grade 3 were significantly lower in CAM-era (grade ≥2, 16% vs. 9.6%, P=0.047; grade ≥3, 3.8% vs. 0.73%, P=0.037). For patients with the pretreatment predictable high-risk factors, the rate of radiation pneumonitis ≥ grade 3 was significantly lower, and that of grade ≥2 had a lower tendency (grade ≥3, 7.2% vs. 0%, P=0.011; grade ≥2, 21% vs. 9.6%, P=0.061). For patients developing early onset radiation pneumonitis, the rate of radiation pneumonitis ≥ grade 3 was also significantly lower (23% vs. 0%, P<0.05). Multivariate analysis revealed that dose-volumetric factor, the pretreatment predictable high-risk factors and non-CAM-administration era were significantly associated with or trended toward radiation pneumonitis ≥ grade 2 and ≥ grade 3. CAM mitigated radiation pneumonitis following SBRT. The efficacy of CAM should be confirmed in prospective studies.

MA 09.08 Receipt of Chest Radiation and Immune-Related Pneumonitis in Patients with NSCLC Treated with Anti-PD-1/PD-L1

MA 09.08 Receipt of Chest Radiation and Immune-Related Pneumonitis in Patients with NSCLC Treated with Anti-PD-1/PD-L1

P3.14-012 Risk of Developing Pneumonitis Increases in Patients Receiving Immunotherapy with a History of Lung Irradiation

A large proportion of patients with locally advanced/metastatic Non-Small Cell Lung Cancer (NSCLC) present disease progression despite aggressive treatments and will further receive immunotherapy. Pneumonitis is an uncommon but potentially fatal toxicity related to immunotherapy treatment. The association with the history of radiotherapy and the risk of developing pneumonitis have not been well described. We associated the history of radiotherapy with the development of pneumonitis in patients receiving immunotherapy.

Severe Pneumonitis in Patient with Kidney Cancer Using Nivolumab after Influenza Vaccine - A Case Report

Immunotherapies are new drugs that are revolutionizing the treatment of many malignancies, among them, the kidney cancer. Because of their mechanism of action they can trigger an important inflammatory responses and immune-mediated adverse events. The safety of influenza vaccination during the use of checkpoint inhibitors is not defined. We report the case of a patient with kidney cancer who evolved unfavorably a few days after receiving the influenza immunization without the consent of the oncology specialists.