scholarly journals Association between the type of thyroid dysfunction induced by immune checkpoint inhibitors and prognosis in cancer patients

2021 ◽  
Author(s):  
Han-sang Baek ◽  
Chaiho Jeong ◽  
Kabsoo Shin ◽  
Jaejun Lee ◽  
Dong-Jun Lim ◽  
...  
Keyword(s):  
Subclinical Hypothyroidism ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Hazard Ratio ◽  
Cancer Type ◽  
Significant Difference ◽  
The Difference ◽  
Lower Hazard

Abstract Background Immune checkpoint inhibitors (ICIs) cause thyroid immune-related adverse effects (irAEs). However, associations between each type of thyroid immune-related adverse effect (irAE) and the anti-tumor effect of ICI remains unknown. This study aimed to determine the effects of each type of thyroid dysfunction on patient survival. Methods Patients who initiated ICI treatment from January 2015 to December 2019 in Seoul St. Mary’s Hospital were retrospectively analyzed. Thyroid dysfunction was classified into four types: newly developed overt or subclinical hypothyroidism, thyrotoxicosis, worsened hypothyroidism, and subclinical hyperthyroidism. Patients were divided into two groups according to the presence or absence of thyroid dysfunction. Results Among the 196 patients, 66 (33.7%) developed thyroid irAEs. There was no significant difference in age, sex, or cancer type between the two groups. The overall survival in patients with thyroid irAEs was significantly higher than that in patients without thyroid irAEs (38 months vs. 13 months, respectively, p = 0.005). After adjusting for confounding factors, the hazard ratio for mortality in the thyroid irAE group compared to the no thyroid irAE group was 0.520 (p = 0.007). Newly developed overt or subclinical hypothyroidism patients showed a significantly lower hazard ratio for morbidity of 0.309 (p = 0.001). Patients with thyrotoxicosis showed a worse hazard ratio for morbidity than those without thyroid irAE, although the difference was not statistically significant. Conclusions It was verified that ICI treatment-induced thyroid dysfunction was associated with better survival, even in the real-world practice. Thus, endocrinologists should cooperate with oncologists to monitor patients treated with ICIs.

scholarly journals Chromosomal Instability May Not Be a Predictor for Immune Checkpoint Inhibitors from a Comprehensive Bioinformatics Analysis

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 276
Author(s):  
Chiao-En Wu ◽  
Da-Wei Yeh ◽  
Yi-Ru Pan ◽  
Wen-Kuan Huang ◽  
Ming-Huang Chen ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Predictive Value ◽  
Chromosomal Instability ◽  
Immune Checkpoint Inhibitors ◽  
Bioinformatics Analysis ◽  
Checkpoint Inhibitors ◽  
P Value ◽  
Cancer Type ◽  
Significant Difference ◽  
The Impact

Immune checkpoint inhibitors (ICIs) have become the standard of care in various cancers, although their predictive tools have not yet completely developed. Here, we aimed to exam the role of 70-gene chromosomal instability signature (CIN70) in cancers, and its association with previous predictors, tumor mutation burden (TMB), and microsatellite instability (MSI), for patients undergoing ICIs, as well as the possible predictive value for ICIs. We examined the association of CIN70 with TMB and MSI, as well as the impact of these biomarkers on the survival of 33 cancer cohorts from The Cancer Genome Atlas (TCGA) databank. The predictive value of the ICIs of CIN70 in previously published reports was also validated. Using the TCGA dataset, CIN70 scores were frequently (either positively or negatively) associated with TMB, but were only significantly associated with MSI status in three types of cancer. In addition, our current study showed that all TMB, MSI, and CIN70 had their own prognostic values for survival in patients with various cancers, and that they could be cancer type-specific. In two validation cohorts (melanoma by Hugo et al. and urothelial cancer by Snyder et al.), no significant difference of CIN70 scores was found between responders and non-responders (p-value = 0.226 and 0.108, respectively). In addition, no overall survival difference was noted between patients with a high CIN70 and those with a low CIN70 (p-value = 0.106 and 0.222, respectively). In conclusion, the current study, through a comprehensive bioinformatics analysis, demonstrated a correlation between CIN70 and TMB, but CIN70 is not the predictor for cancer patients undergoing ICIs. Future prospective studies are warranted to validate these findings.

Incidence of Immune Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitors, Case Series from Two Tertiary Care Centeers in Dubai, UAE

2020 ◽  
Vol 106 (1_suppl) ◽  
pp. 25-25
Author(s):  
M Omara ◽  
Elamin Abdelgadir ◽  
F Khan ◽  
M F Latif ◽  
Fatheya Alawadi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Cancer Type ◽  
American Hospital ◽  
Advanced Malignancy ◽  
Grade Ii ◽  
Grade Iii

Introduction: Immune checkpoint inhibitors (ICI) represent a major component of systemic therapy in advanced malignancy. Studies have reported unique spectrum of toxicity profile of ICI as compared to systemic chemotherapy. Aim of this study is to evaluate toxicities of ICI in our population and to compare this with published data. Material and Methods: We retrospectively reviewed medical records of patients treated with ICI at Dubai hospital and American hospital Dubai from November 2015 to April 2019. After patient identification from hospitals cancer registry, data regarding patients’ demographics, cancer type, type of ICI, adverse events, and duration of treatment were collected. Results: Forty-Five patients were identified with median age of 60 (27-80) years. 27 (60%) patients were male and 18 (40%) were female. Underlying diagnosis was lung cancer (n=25), renal cell cancer (n=6), melanoma (n=5), bladder cancer (n=3), Hodgkins lymphoma (n=3) and other malignancies (n=3). Majority of patients received Nivolumab (n=20, 44%) followed by Pembrolizumab (n=19, 42%), Atezolizumab (n=4, 9%) and Durvalumab (n=2, 5%) respectively. Thyroid dysfunction was the most common side effect observed in 17 (38%) patients including hypothyroidism (n=12, 27%) and hyperthyroidism (n=5, 11%). 53 % patients treated with Nivolumab developed thyroid dysfunction as compared to Pembrolizumab (22%). 7 patients (16%) had elevated liver enzymes. Grade II and III hepatotoxicity was noted in 1 patient (2.2 %) each. One patient (2.2 %) developed grade II skin toxicity. One patient (2.2 %) developed grade III colitis. Grade II, III and IV pneumonitis was observed in 2 (4.4 %), 1 (2.2%) and 1 (2.2%) patient respectively. Immune mediated adverse events were managed according to standard guidelines and 2 patients (4.4 %) had treatment discontinuation due to grade IV Pneumonitis and grade III Colitis. Conclusion: Our study reports relatively higher incidence of thyroid adverse events in patients treated with ICI. The incidence of grade III-IV immune related toxicity remains low. Overall treatment with ICI was tolerated reasonably well and toxicity was manageable.

The Current Role of Immunotherapy in mCRPC: A Systematic Review

2021 ◽  
Vol 8 (7) ◽  
Author(s):  
Dalibey H ◽  
◽  
Hansen TF ◽  
Zedan AH ◽  
◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Specific Antigen ◽  
Treatment Modalities ◽  
Significant Difference

Background: The development of immunotherapy has shown promising results in several malignant diseases, including prostate cancer, calling for a systematic review of the current literature. This review aims to evaluate the present data and prospects of immune checkpoint inhibitors in metastatic Castration Resistant Prostate Cancer (mCRPC). Methods: Articles were identified via a systematic search of the electronic database Pubmed, in accordance with the PICO process and following the PRISMA guidelines. Articles in English studying immune checkpoint inhibitors in patients with mCRPC published between March 2010 and March 2020 were eligible for inclusion. Endpoints of interest were Overall Survival (OS), Progression-Free Survival (PFS), clinical Overall Response Rate (ORR), and Prostate-Specific Antigen (PSA) response rate. Results: Ten articles were identified as eligible for inclusion. The studies primarily explored the use of Ipilimumab, a CTLA-4 inhibitor, and Pembrolizumab, a PD-1 inhibitor. These drugs were both used either as monotherapy or in combination with other treatment modalities. The largest trial included in the review demonstrated no significant difference in overall survival between the intervention and placebo. However, two studies presented promising data combing immunotherapy and immune vaccines. Grade 3 and 4 adverse events ranging from 10.1% to 82.3%, whit diarrhea, rash, and fatigue were the most frequently reported. Forty relevant ongoing trials were identified exploring immunotherapy with or without a parallel treatment modality. Conclusion: Overall, the current data shows that the effect of immune checkpoint inhibitors as monotherapy may have limited impact on mCRPC, and the results from ongoing combinational trials are eagerly awaited.

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

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

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

Abstract 14600: Pre-existing Autoimmune Disease and the Risk for Cardiovascular and Non-cardiovascular Immune Mediated Adverse Events With Immune Checkpoint Inhibitors

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Charlotte Lee ◽  
Zsofia D Drobni ◽  
Amna Zafar ◽  
Raza M Alvi ◽  
Sean P Murphy ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Autoimmune Disease ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Cardiovascular Events ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Skin Toxicity ◽  
Significant Difference

Introduction: The use of immune checkpoint inhibitors (ICIs) is associated with an increase in cardiovascular events. The mechanism is likely related to immune activation and inflammation. Patients with pre-existing autoimmune disease have a baseline increased risk for cardiovascular disease and have been traditionally excluded from clinical trials of ICIs. There is limited data on the cardiovascular and non-cardiovascular safety of ICIs in these patients. Methods: This was a retrospective study of 2845 patients treated with an ICI at the Massachusetts General Hospital. This cohort was screened by individual chart review for patients with a diagnosis of an autoimmune disease prior to ICI therapy. These autoimmune patients were compared to controls at a 1:2 ratio. Baseline characteristics and risk of cardiovascular and non-cardiovascular immune related adverse events (iRAEs) were compared. Cardiovascular events were a composite of myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), stroke, transient ischemic attack (TIA), deep venous thrombosis (DVT), pulmonary embolism (PE), or myocarditis. Results: 93 patients had a diagnosis of an autoimmune disease prior to ICI. These patients were more likely to be older and to have a history of coronary artery disease, heart failure, chronic kidney disease, hypertension and diabetes mellitus. There were 12 events over a median follow-up period of 300 days. There was no significant difference in composite of cardiovascular events in follow-up (13 vs. 9.1%, autoimmune vs. none, P =0.41). The individual cardiovascular event rates were as follows: MI (4.3 vs. 0.5%, P =0.04), PCI (0 vs. 0.5%, P =1), CABG (0. vs. 0.5%, P =1), stroke (0 vs. 0%), TIA (0 vs. 0.5%, P =1), DVT (5.4 vs. 2.2%, P =0.17), PE (1.1 vs. 4.8%, P =0.17), and myocarditis (2.2 vs. 1.1%, P =0.60). There was an increased rate of pneumonitis (14 vs. 4%, P <0.001) and skin toxicity (16 vs. 0%, P <0.001). Conclusions: Patients with pre-existing autoimmune disease treated with an ICI had a higher baseline cardiovascular risk but did not have a significant increase in cardiovascular events in an unadjusted analysis. These patients did, however, have an increased rate of pneumonitis and skin toxicity after ICI.

Optimizing Sequence of PD-L1 Immune-Checkpoint Inhibitors and Radiation Therapy in Bladder Cancer

2020 ◽  
Vol 6 (3) ◽  
pp. 295-302
Author(s):  
Côme Tholomier ◽  
Gautier Marcq ◽  
Surashri Shinde-Jadhav ◽  
Mina Ayoub ◽  
Jia Min Huang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radiation Therapy ◽  
Tumor Growth ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Combined Therapy ◽  
Tumor Growth Rate ◽  
Significant Difference ◽  
Rate Of Response

BACKGROUND: New bladder preserving strategies are needed for muscle invasive bladder cancer (MIBC). Combined therapy of immune-checkpoint inhibitors and radiation was shown to have synergistic antitumoral effects in preclinical studies. OBJECTIVES: We aim to evaluate whether the sequence of administration of this combined therapy impacts antitumoral response. METHODS: We developed an in-vivo syngeneic MIBC mouse model where murine bladder cancer cells (MB49) were injected subcutaneously in the right flank of C57BL/6 mice. Mice were then randomized to the following treatments: control, anti-programmed cell death ligand 1 (PD-L1) alone, radiation alone (XRT) consisting of 6.25 Gy x2 fractions, concurrent anti-PD-L1 with XRT, neoadjuvant anti-PD-L1 followed by XRT, or XRT followed by adjuvant anti-PD-L1 therapy. Tumor growth, survival, and rate of response were analyzed. RESULTS: Total of 60 mice were randomized. One-way analysis of variance showed statistically significant difference in tumor growth rate across the treatment arms (p = 0.029). Importantly, timing of immunotherapy (neoadjuvant, concurrent, or adjuvant) did not alter either tumor growth or survival (p > 0.05). The rate of response was also similar in each combination arm (p > 0.05). CONCLUSION: Combining anti-PD-L1 immunotherapy and radiation therapy offers optimal antitumoral responses. Timing of immunotherapy (neoadjuvant, concurrent, or adjuvant) does not appear to affect outcomes. Whether the toxicity profile differs across various sequential deliveries of combination therapy requires further evaluation.

Malignant melanoma followed by the development of type I diabetes and thyroid dysfunction caused by immune checkpoint inhibitors : Two case reports

Skin Cancer ◽  
2018 ◽  
Vol 33 (1) ◽  
pp. 22-29
Author(s):  
Aya TAKAHASHI ◽  
Masato AMAKATA ◽  
Yoshiki SATO ◽  
Megumi YOKOYAMA ◽  
Kaduhisa HIRAHARA ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Type I Diabetes ◽  
Case Reports ◽  
Type I

Risk factors for myocarditis associated with immune checkpoint inhibitors using real-world clinical data.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15100-e15100 ◽  
Author(s):  
Prantesh Jain ◽  
Jahir Gutierrez Bugarin ◽  
Avirup Guha ◽  
Chhavi Jain ◽  
Tingke Shen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Disease ◽  
Cancer Patients ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cox Proportional Hazards ◽  
Cancer Type ◽  
Real World Data

e15100 Background: Immune checkpoint inhibitors (ICIs) can cause unique, high-grade immune-related adverse events. Although rare, ICI related myocarditis has the highest fatality rate (~50%). Cardiovascular monitoring is not routinely performed in patients on ICI treatment, thus risk factors remain unknown. Characterizing rare but fatal cardiac toxicities requires integration of real-world data. Methods: U.S claims data (IBM MarketScan) of over 30 million commercially insured individuals was leveraged to identify 2,687,301 cancer patients between 2011-2018. Patients ≥18 years of age treated with ICIs (targeting CTLA4 (ipilimumab) and/or the PD1 (nivolumab, pembrolizumab)/PDL1 (atezolizumab, avelumab, durvalumab) alone or in combination with ICI and/or chemotherapy were identified and followed until disenrollment. Myocarditis, comorbidities, and treatment details were identified using diagnosis and billing codes. Analyses included descriptive statistics and Cox proportional hazards regression. Results: 16,541 ICI treated cancer patients were included (median age 60; 58% male). Myocarditis was identified in 252 (1.5%) patients, majority (90%) ≥50 years old (median 63) with 12,040 person-years of follow up. 62% received anti-PD1 monotherapy, 12% anti-CTLA4, and 15% received combination treatment with other ICIs and/or chemotherapy. Most common cancer types were lung (48%), melanoma (25%), and renal cancer (14%). Cumulative incidence of myocarditis at 1 year was 2.06%; 95% CI (1.78-2.37), median onset of 80.5 days, 42% occurring within 60 days of treatment. By univariate analyses, age, cancer type, diabetes (DM), hypertension (HTN), kidney, liver disease, atrial fibrillation (AF) were related to myocarditis. Risk was lower in patients who received anti-CTLA4 monotherapy (HR: 0.490; 95% CI: 0.26-0.92; p = 0.0251). On multivariable regression analyses only age, cancer type (renal, lung cancer), comorbidities DM and liver disease were significantly associated with myocarditis (Table). Conclusions: This is the largest real-world longitudinal study for ICI associated myocarditis showing higher than reported incidence and identifiable risk factors. [Table: see text]

scholarly journals Case Report: Cardiac Toxicity Associated With Immune Checkpoint Inhibitors

2021 ◽  
Vol 8 ◽  
Author(s):  
Ru Chen ◽  
Ling Peng ◽  
Zhihua Qiu ◽  
Yan Wang ◽  
Fen Wei ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Troponin I ◽  
Systemic Corticosteroid ◽  
Checkpoint Inhibitors ◽  
Cardiac Conduction ◽  
Fulminant Myocarditis ◽  
Cancer Type ◽  
Life Threatening ◽  
The Subject

Immune checkpoint inhibitors (ICIs) have now emerged as a mainstay of treatment for various cancer. Along with the development of ICIs, immune-related adverse effects (irAEs) have been the subject of wide attention. The cardiac irAE, a rare but potentially fatal and fulminant effect, have been reported recently. This article retrospectively reviewed 10 cases from our hospital with cardiac irAEs, with severity ranging from asymptomatic troponin-I elevations to cardiac conduction abnormalities and even fulminant myocarditis. In our series, all the cases were solid tumors and lung cancer was the most frequent cancer type (4,40%). In total, three (30.0%) patients experienced more than one type of life-threatening complication. A systemic corticosteroid was given to nine patients (90.0%). The majority of cases (7, 70%) were performed at an initial dose of 1–2 mg/kg/day. Two (20.0%) patients were admitted to ICU, three (30.0%) patients were put on mechanical ventilation, two (20.0%) patients received the plasma exchange therapy, and one patient was implanted with a pacemaker. Two (20.0%) of the patients succumbed and died, with a median duration of 7.5 days (IQR5.0–10.0) from diagnosis of cardiac irAE to death. Based on these results, we recommend that clinicians be alert to cardiac irAEs, including performing cardiovascular examinations before ICI treatment to accurately diagnose suspected myocarditis, enabling immediate initiation of immunosuppressive therapy to improve prognosis.

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