Rates of immunosuppressive treatment and hospitalization after checkpoint inhibitor therapy in melanoma and lung cancer patients with autoimmune diseases.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14140-e14140
Author(s):  
David Andrew Bender ◽  
Catherine Spina ◽  
Samuel P. Heilbroner ◽  
Eric Xanthopoulos ◽  
Tony J. C. Wang ◽  
...  

e14140 Background: Immune checkpoint inhibitors (ICIs) are known to cause immune-related adverse events. Patients with autoimmune diseases (AID) were excluded from most ICI clinical trials due to the potentially high risk of adverse effects. Data on the safety of ICIs in patients with a diagnosis of AID is therefore limited. Methods: A retrospective cohort study was conducted using a de-identified large oncology health care and pharmacy claims database with data from March 2010 until April 2017. Patients analyzed had a diagnosis of either melanoma or lung cancer and were treated with either of the anti-PD-1 inhibitors nivolumab or pembrolizumab. We assessed whether patients with AID compared with no AID were more likely to require medical interventions within 180 days of ICI therapy. We determined the percentage of patients receiving oral prednisone, IV methylprednisolone, or were hospitalized, which may represent responses to ICI toxicity. Results: 16.7% (16/96) of patients with either melanoma or lung cancer and AID received oral prednisone treatment within 180 days of ICI treatment, while 8.3% (131/1573) of patients without AID received oral prednisone during the same period. 8.4% (16/190) of patients with AID received IV methylprednisolone compared to 3.6% (79/2190) of patients without AID. Among melanoma patients, 24.1% (13/54) of patients with AID were hospitalized following ICI treatment, compared to 5.8% (28/480) of patients without ICI. Among lung cancer patients, 38.2% (52/136) of patients with AID were hospitalized compared to 31.6% (541/1711) of patients without AID. All comparisons are significant at p < 0.05 except hospitalizations in lung cancer patients. Conclusions: Patients with AID were more likely to receive interventions after ICI treatment that may represent responses to immune-related adverse events, suggesting that patients with AID are at increased risk for toxicity when being treated with ICIs.

2021 ◽  
Vol 11 ◽  
Author(s):  
Donghui Wang ◽  
Cen Chen ◽  
Yanli Gu ◽  
Wanjun Lu ◽  
Ping Zhan ◽  
...  

BackgroundImmune-related adverse events (irAEs) have been reported to be associated with the efficacy of immunotherapy. Herein, we conducted a meta-analysis to demonstrate that irAEs could predict the efficacy of immune checkpoint inhibitors (ICIs) in lung cancer patients.MethodsLiterature on the correlation between irAEs and the efficacy of immunotherapy in lung cancer patients were searched to collect the data on objective response rate (ORR), overall survival (OS), or progression-free survival (PFS) of the patients. These data were incorporated into the meta-analysis.ResultsA total of 34 records encompassing 8,115 patients were examined in this study. The irAEs occurrence was significantly associated with higher ORR {risk ratio (RR): 2.43, 95% confidence interval (CI) [2.06–2.88], p &lt; 0.00001} and improved OS {hazard ratio (HR): 0.51, 95% CI [0.43–0.61], p &lt; 0.00001}, and PFS (HR: 0.50, 95% CI [0.44–0.57], p &lt; 0.00001) in lung cancer patients undergoing ICIs. Subgroup analysis revealed that OS was significantly longer in patients who developed dermatological (OS: HR: 0.53, 95%CI [0.42–0.65], p &lt; 0.00001), endocrine (OS: HR: 0.55, 95%CI [0.45–0.67], p &lt; 0.00001), and gastrointestinal irAEs (OS: HR: 0.58, 95%CI [0.42–0.80], p = 0.0009) than in those who did not. However, hepatobiliary, pulmonary, and high-grade (≥3) irAEs were not correlated with increased OS and PFS.ConclusionThe occurrence of irAEs in lung cancer patients, particularly dermatological, endocrine, and gastrointestinal irAEs, is a predictor of enhanced ICIs efficacy.


2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 207-207
Author(s):  
Nadine Abdallah ◽  
Suketu Nagin Patel ◽  
Misako Nagasaka ◽  
Seongho Kim ◽  
Harold E. Kim ◽  
...  

207 Background: Checkpoint inhibitors exert their antitumor effects by producing a heightened immune state, and inadvertently give rise to immune-mediated toxicities, including pneumonitis and hypothyroidism. We investigated whether these side effects were more common in patients who were treated with both PD-1 inhibitors and radiation. Methods: Our institution’s pharmacy database was used to collect data on patients who received ≥ 1 dose of PD-1 inhibitors, with or without radiation before August 31, 2016. Adverse effects of hypothyroidism, and pneumonitis were recorded and graded based on CTCAEv4. A logistic regression analysis was performed between radiation and hypothyroidism among patients with Hodgkin’s lymphoma (HL) and head and neck squamous cell carcinoma (HNSCC) and between radiation therapy (RT) and pneumonitis in lung cancer patients. Results: 231 patients received at least one dose of PD-1 inhibitors prior to data cut-off. Median age was 65 (24-92). There were 125 patients (54%) with lung cancer, 18 (8%) with HL and 9 (4%) with HNSCC. 115 patients received radiation. HL and HNSCC patients had higher odds to experience hypothyroidism (adjusted p = 0.023) but this did not seem to be due to RT exposure [HR:0.156, 95% CI 0.008-1.122, p = 0.110]. Lung cancer patients with thoracic radiation had higher odds to experience pneumonitis [HR:2.206, 95% CI 0.451-15.931] although this was not statistically significant (p = 0.358). Conclusions: There was no association between RT and hypothyroidism. Our results suggested a possible increased risk of pneumonitis with thoracic radiation among lung cancer patients treated with PD-1 inhibitors, although statistically insignificant. Larger prospective studies are needed to further delineate this effect.


Author(s):  
Da Hyun Kang ◽  
Chaeuk Chung ◽  
Pureum Sun ◽  
Da Hye Lee ◽  
Song-I Lee ◽  
...  

Abstract Background Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the frequency of pseudoprogression and hyperprogression in lung cancer patients treated with ICIs in the real world and aimed to discover a novel candidate marker to distinguish pseudoprogression from hyperprogression soon after ICI treatment. Methods This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes. Results The incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4+CD25+CD127loFoxP3+ Treg cells was significantly decreased compared with baseline (P = 0.038) in patients who experienced pseudoprogression and significantly increased compared with baseline (P = 0.024) in patients who experienced hyperprogression. In the responder group, the frequencies of CD4+CD25+CD127loFoxP3+ Treg cells and PD-1+CD4+CD25+CD127loFoxP3+ Treg cells were significantly decreased 7 days after commencement of treatment compared with baseline (P = 0.034 and P < 0.001, respectively). Conclusion Circulating Treg cells represent a promising potential dynamic biomarker to predict efficacy and differentiate atypical responses, including pseudoprogression and hyperprogression, after immunotherapy in patients with NSCLC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Po-Hsin Lee ◽  
Tsung-Ying Yang ◽  
Kun-Chieh Chen ◽  
Yen-Hsiang Huang ◽  
Jeng-Sen Tseng ◽  
...  

AbstractPleural effusion is a rare immune-related adverse event for lung cancer patients receiving immune checkpoint inhibitors (ICIs). We enrolled 281 lung cancer patients treated with ICIs and 17 were analyzed. We categorized the formation of pleural effusion into 3 patterns: type 1, rapid and massive; type 2, slow and indolent; and type 3, with disease progression. CD4/CD8 ratio of 1.93 was selected as the cutoff threshold to predict survival. Most patients of types 1 and 2 effusions possessed pleural effusion with CD4/CD8 ratios ≥ 1.93. The median OS time in type 1, 2, and 3 patients were not reached, 24.8, and 2.6 months, respectively. The median PFS time in type 1, 2, and 3 patients were 35.5, 30.2, and 1.4 months, respectively. The median OS for the group with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were not reached and 2.6 months. The median PFS of those with pleural effusion CD4/CD8 ≥ 1.93 and < 1.93 were 18.4 and 1.2 months. In conclusion, patients with type 1 and 2 effusion patterns had better survival than those with type 3. Type 1 might be interpreted as pseudoprogression of malignant pleural effusion. CD4/CD8 ratio ≥ 1.93 in pleural effusion is a good predicting factor for PFS.


2019 ◽  
Vol 166 (4) ◽  
pp. 323-329 ◽  
Author(s):  
Randa H Mohamed ◽  
Heba F Pasha ◽  
Doaa M Gad ◽  
Mostafa M Toam

AbstractRecently, MicroRNAs polymorphisms and their serum expression have been linked to increase risk of various cancers. The aim of this study was to elucidate the association between single nucleotide polymorphisms of miR-146a and miR-196a-2 and their serum expression and lung cancer risk. One hundred and twenty lung cancer patients and 120 health controls were included in this study. Genotyping and expression for miR-146a and miR-196a-2 were performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and quantitative real-time PCR. Individuals carrying miR-146a CG and CC genotypes had significantly increased risk for lung cancer than those carrying miR-146a GG genotype. MiR-146a expression significantly decreased in miR-146a CG and CC genotypes carriers as compared with GG genotype carriers. MiR-196a-2 CT and TT genotypes were significantly associated with increased lung cancer while the highest expression of MiR-196a-2 was detected in miR-196a-2 CC genotype carriers. Serum miR-146a was significantly decreased in lung cancer patients while serum miR-196a-2 expression was significantly increased in lung cancer patients. In conclusion, miR-146a and miR-196a-2 genes polymorphisms and their circulating levels were associated with lung cancer risk in Egyptians and may be helpful in early detection of lung cancer.


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