scholarly journals Cardiotoxicity associated with immune checkpoint inhibitors: A retrospective analysis of patients at an academic tertiary care center

2020 ◽  
Author(s):  
Nida Waheed ◽  
Michael G. Fradley ◽  
David DeRemer ◽  
Ahmad Mahmoud ◽  
Chintan P. Shah ◽  
...  
Keyword(s):  
Heart Failure ◽  
Anticancer Agents ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Beta Blockers ◽  
Care Center ◽  
Tertiary Care ◽  
Data Repository ◽  
Pericardial Disease

Abstract Background: Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of ICI-related cardiotoxicity in patients treated with ICIs at a large, tertiary care center.Methods: All patients with a cancer diagnosis who received any ICI treatment in the University of Florida’s Integrated Data Repository from 2011-2017 were included. Cardiotoxicity was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment.Results: Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one possible form of cardiotoxicity after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Cardiotoxicity was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in those who developed ICI-attributable cardiotoxicity was higher compared to those who did not (66.1% vs. 41.4%, odds ratio=2.77, 1.55-4.95, p=0.0006). There was no evidence that use of cardioprotective agents such as beta-blockers or statins was associated with lower rates of cardiotoxicity or mortality.Conclusions: This study suggests that the incidence of ICI-related cardiotoxicity may be higher than previously reported.

scholarly journals Cardiotoxicity associated with immune checkpoint inhibitors: A retrospective analysis of patients at an academic tertiary care center

2020 ◽  
Author(s):  
Nida Waheed ◽  
Michael G. Fradley ◽  
David DeRemer ◽  
Ahmad Mahmoud ◽  
Chintan P. Shah ◽  
...  
Keyword(s):  
Heart Failure ◽  
Anticancer Agents ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Care Center ◽  
Tertiary Care ◽  
Data Repository ◽  
Tertiary Care Center ◽  
Pericardial Disease

Abstract Background Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of ICI-related cardiotoxicity in patients treated with ICIs at a large, tertiary care center. Methods All patients with a cancer diagnosis who received any ICI treatment in the University of Florida’s Integrated Data Repository from 2011-2017 were included. Cardiotoxicity was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment. Results Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one possible form of cardiotoxicity after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Cardiotoxicity was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in those who developed ICI-attributable cardiotoxicity was higher compared to those who did not (66.1% vs. 41.4%, odds ratio=2.77, 1.55-4.95, p=0.0006). Conclusions This study suggests that the incidence of ICI-related cardiotoxicity may be higher than previously reported.

scholarly journals Newly diagnosed cardiovascular disease in patients treated with immune checkpoint inhibitors: a retrospective analysis of patients at an academic tertiary care center

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Nida Waheed ◽  
Michael G. Fradley ◽  
David L. DeRemer ◽  
Ahmad Mahmoud ◽  
Chintan P. Shah ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Care Center ◽  
Tertiary Care ◽  
Tertiary Care Center ◽  
Newly Diagnosed ◽  
Incident Cardiovascular Disease

Abstract Background Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of newly diagnosed cardiovascular disease in patients treated with ICIs at a large, tertiary care center. Methods All patients with a cancer diagnosis who received any ICI treatment in the University of Florida’s Integrated Data Repository from 2011 to 2017 were included. Cardiovascular disease was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment. Results Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one new cardiovascular disease after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Incident cardiovascular disease was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in ICI treated patients with a concomitant diagnosis of incident cardiovascular disease was higher compared to those who did not (66.1% vs. 41.4%, odds ratio = 2.77, 1.55–4.95, p = 0.0006). Conclusions This study suggests a high incidence of newly diagnosed cardiovascular disease after the initiation of ICI therapy in a real-world clinical setting.

scholarly journals Cardiotoxicity associated with immune checkpoint inhibitors: A retrospective analysis of patients at an academic tertiary care center

2020 ◽  
Author(s):  
Nida Waheed ◽  
Michael G. Fradley ◽  
David DeRemer ◽  
Ahmad Mahmoud ◽  
Chintan P. Shah ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Care Center ◽  
Tertiary Care ◽  
Tertiary Care Center ◽  
Newly Diagnosed ◽  
Incident Cardiovascular Disease

Abstract Background Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of newly diagnosed cardiovascular disease ICI-related cardiotoxicity in patients treated with ICIs at a large, tertiary care center. Methods All patients with a cancer diagnosis who received any ICI treatment in the University of Florida’s Integrated Data Repository from 2011-2017 were included. Cardiovascular disease was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment. Results Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one new cardiovascular disease after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Incident cardiovascular disease was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in ICI treated patients with a concomitant diagnosis of incident cardiovascular disease was higher compared to those who did not (66.1% vs. 41.4%, odds ratio = 2.77, 1.55-4.95, p = 0.0006). Conclusions This study suggests a high incidence of newly diagnosed cardiovascular disease after the initiation of ICI therapy.

Abstract 12563: Retrospective Analysis of Cardiovascular Events With the Use of Immune Checkpoint Inhibitors

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tushar Tarun ◽  
Brian P Bostick ◽  
Deepa Baswaraj ◽  
Nishchayjit Basra ◽  
Meeshal Khan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Retrospective Analysis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Multiple Organ ◽  
Fulminant Myocarditis ◽  
Organ Systems ◽  
History Of

Introduction: Immune checkpoint inhibitors have emerged as a promising, novel therapy for multiple malignancies. Immune-related adverse reactions pose a serious concern with use of these agents and reportedly involve multiple organ systems, notably cardiotoxicity. Early identification and management of these adverse events is essential in the prevention of morbidity and mortality. Hypothesis: Immune checkpoint inhibitors cause multiple cardiotoxic effects, and patients with prior cardiac history have a higher likelihood of cardiotoxicity. Methods: 1. A retrospective analysis of 150 patients was performed who had received immunotherapy with either the cytotoxic T lymphocyte associated antigen 4 inhibitors (CTLA4) or with the programmed cell death inhibitors (PD1) or programmed death-ligand 1 (PD-L1) inhibitors for a period of two years at a Tertiary health Care from 7/1/2016-6/30/2018. 2. Patients' cardiac diagnoses prior to the initiation of therapy were noted and included, including history of heart failure, coronary artery disease, atrial fibrillation, and sudden cardiac arrest. 3. Patients’ clinic visits and hospitalizations with admitting and discharge diagnosis, electrocardiogram, echocardiogram, troponin T, and NT-proBNP were reviewed. Results: 6% of patients had new onset heart failure (both preserved and reduced), 1.3% had evidence of myocardial infarction, 2% had new atrial fibrillation with rapid ventricular rate, and 0.6% had fulminant myocarditis. Of patients with new cardiac events, 60% had a history of cardiac disease, which was significantly higher than in patients without (p< 0.05). There were no age or sex differences between the groups with and without cardiotoxicity. Conclusion: Immunotherapy with immune checkpoint inhibitors have broadened the horizon for treatment of multiple solid and hematological malignancies. Nonetheless, new adverse effects on multiple organ systems, specifically cardiac involvement, occur with these therapies, which are important and potentially detrimental toxicities. Patients with a history of prior cardiovascular disease have higher likelihood to develop cardiotoxicity.

scholarly journals Risk factors for cancer-associated thrombosis in patients undergoing treatment with immune checkpoint inhibitors

2019 ◽  
Vol 38 (4) ◽  
pp. 1200-1206 ◽  
Author(s):  
Yosuke Ando ◽  
Takahiro Hayashi ◽  
Reiko Sugimoto ◽  
Seira Nishibe ◽  
Kaori Ito ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Heart Disease ◽  
Anticancer Agents ◽  
Immune Checkpoint ◽  
Odds Ratio ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
History Of ◽  
Cancer Associated Thrombosis

SummaryPurpose Anticancer agents are known to increase cancer-associated thrombosis (CAT) onset. CAT onset rate is reported to be 1.92% in cisplatin-based therapy, 6.1% in paclitaxel plus ramucirumab combination therapy, and 11.9% in bevacizumab monotherapy. Because immune checkpoint inhibitors (ICIs) cause a sudden increase in T cell number, an association between administration of these drugs and increase in CAT incidence is likely. However, the extent to which ICI administration affects CAT incidence remains unclear. Further, risk factors for CAT incidence have not yet been identified. The present study investigated CAT incidence and associated risk factors in patients receiving ICI. Methods Patients administered nivolumab or pembrolizumab at Fujita Health University Hospital from April 2017 to March 2018 were enrolled. We collected retrospective data regarding age, sex, cancer type, BMI, medical history, laboratory data at treatment initiation, medications, and computed tomography (CT) interpretations from electronic medical records. Results We identified 122 eligible participants from 135 patients receiving nivolumab or pembrolizumab. Ten patients (8.2%) developed CAT. A history of venous thromboembolism (VTE) or arterial thromboembolism (ATE) was a risk factor for CAT incidence (odds ratio: 6.36, P = 0.039). A history of heart disease may be a risk factor for CAT incidence (odds ratio 6.56, P = 0.052). Significantly higher usage of antiplatelet and anticoagulant therapy was noted in patients who developed CAT (60%) than in those who did not (13.4%, p < 0.01). Conclusion High (8.2%) CAT incidence during ICI administration suggested that ICI is not associated with a lower blood clot risk than other anticancer agents investigated in previous studies. For patients with VTE, ATE, or heart disease history, it is crucial to consider the possibility of CAT even with antiplatelet therapy.

Efficacy of immune checkpoint inhibitors in patients with brain metastasis from NSCLC, RCC, and melanoma.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 214-214 ◽  
Author(s):  
Adam Lauko ◽  
Bicky Thapa ◽  
Xuefei Jia ◽  
Manmeet Singh Ahluwalia
Keyword(s):  
Brain Metastasis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Tertiary Care ◽  
Multivariable Analysis ◽  
Volumetric Analysis ◽  
Cell Lung Carcinoma ◽  
Combination Methods

214 Background: Immune checkpoint inhibitors are revolutionizing the treatment of multiple advanced malignancies, however, there is limited data on the efficacy of immune checkpoint blockade in brain metastasis. We conducted a study to analyze the overall survival (OS) and progression-free survival (PFS) among patients with brain metastasis from Non-Small Cell Lung Carcinoma (NSCLC), Renal Cell Carcinoma (RCC), and Melanoma treated with either Nivolumab, Pembrolizumab, Ipilimumab or a combination. Methods: After IRB approval, we retrospectively evaluated patients with brain metastasis treated at our tertiary care institution from 2011-2017 who underwent immunotherapy and one or more of the following; whole brain radiation therapy (WBRT), surgery, stereotactic radiosurgery (SRS) or systemic chemotherapy. Univariable and multivariable analysis was utilized to analyze OS and PFS. Volumetric analysis to assess treatment response is ongoing. Results: A total of 128 patients were identified with a median age of 60.6 years. 49% of patients were male; 77% of patients had a good (0 or 1) ECOG performance scores at the time of the brain metastasis; 83 patients had supratentorial brain metastasis, 11 had infratentorial and 24 had both. The prevalence of mutations was 34% in NSCLC patients, 58% in melanoma, and 0% in RCC. The median OS from the start of immunotherapy was not reached for RCC and was 17.1 and 28.9 months for Melanoma and NSCLC respectively. Median PFS was 5.9, 6.7 and 3.6 months for RCC, Melanoma, and NSCLC respectively. On multivariable analysis, SRS, sex and the number of cycles of immunotherapy had statistically significant hazard ratios. Conclusions: Immune checkpoint inhibitors are efficacious in the treatment of brain metastasis. Further analysis including response criteria using volumetric analysis is ongoing and final results will be presented at the meeting. [Table: see text]

scholarly journals Pericardial disease in patients treated with immune checkpoint inhibitors

2021 ◽  
Vol 9 (6) ◽  
pp. e002771
Author(s):  
Jingyi Gong ◽  
Zsofia Dora Drobni ◽  
Amna Zafar ◽  
Thiago Quinaglia ◽  
Sarah Hartmann ◽  
...  
Keyword(s):  
Pericardial Effusion ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cancer Type ◽  
Pericardial Disease ◽  
Fourfold Increase ◽  
Large Pericardial Effusion ◽  
Academic Center ◽  
Increased Risk

BackgroundThere are limited data on the occurrence, associations and outcomes of pericardial effusions and pericarditis on or after treatment with immune checkpoint inhibitors (ICIs).MethodsThis was a retrospective study at a single academic center that compared 2842 consecutive patients who received ICIs with 2699 age- and cancer-type matched patients with metastatic disease who did not receive ICI. A pericardial event was defined as a composite outcome of pericarditis and new or worsening moderate or large pericardial effusion. The endpoints were obtained through chart review and were blindly adjudicated. To identify risk factors associated with a pericardial event, we compared patients who developed an event on an ICI with patients treated with an ICI who did not develop a pericardial event. Cox proportional-hazard model and logistical regression analysis were performed to study the association between ICI use and pericardial disease as well as pericardial disease and mortality. An additional 6-week landmark analysis was performed to account for lead-time bias.ResultsThere were 42 pericardial events in the patients treated with ICI (n=2842) over 193 days (IQR: 64–411), yielding an incidence rate of 1.57 events per 100 person-years. There was a more than fourfold increase in risk of pericarditis or a pericardial effusion among patients on an ICI compared with controls not treated with ICI after adjusting for potential confounders (HR 4.37, 95% CI 2.09 to 9.14, p<0.001). Patients who developed pericardial disease while on an ICI had a trend for increased all-cause mortality compared with patients who did not develop a pericardial event (HR 1.53, 95% CI 0.99 to 2.36, p=0.05). When comparing those who developed pericardial disease after ICI treatment with those who did not, a higher dose of corticosteroid pre-ICI (>0.7 mg/kg prednisone) was associated with increased risk of pericardial disease (HR 2.56, 95% CI 1.00 to 6.57, p=0.049).ConclusionsICI use was associated with an increased risk of development of pericardial disease among patients with cancer and a pericardial event on an ICI was associated with a trend towards increase in mortality.

Examining the real-world utility of immune checkpoint inhibitors in genitourinary oncology: A single-institution retrospective.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17112-e17112
Author(s):  
Lydia Glick ◽  
Cassra Clark ◽  
Timothy M. Han ◽  
James Ryan Mark ◽  
Leonard G. Gomella ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Tertiary Care ◽  
University Hospital ◽  
Rank Test ◽  
Single Institution ◽  
Number Of Patients

e17112 Background: Immune Checkpoint Inhibitors (ICI) are increasingly utilized for genitourinary (GU) malignancies. However, data is lacking on the efficacy of these drugs in “real-world” populations - patients who do not fit the strict clinical trial criteria, but may still benefit from therapy. We performed a retrospective analysis of patients receiving ICI at a single tertiary-care institution, with special attention to clinical trial enrollment, adverse events, progression and survival. Methods: Patients receiving ICI for GU malignancies at Thomas Jefferson University Hospital from January 2017 to January 2019 were identified. Descriptive statistics of treatment and pathologies were performed. Progression-free survival (PFS) was calculated from start of ICI to documentation of progression or last follow-up. PFS and overall survival were assessed using Kaplan Meier log-rank test, stratified by trial enrollment. Results: 111 patients were included: 37 on ICI clinical trial, 70 received ICI “off-trial” and 4 received ICI in both settings. 11 patients (10%) underwent multiple courses of ICI throughout treatment. The number of patients initiating ICI increased annually; by 2018, the number of patients initiated on ICI “off-trial” exceeded those initiating ICI “on-trial” (79% vs 21%). Treated pathology included Urothelial Carcinoma (UC; 42%), Renal Cell Carcinoma (RCC; 28%), and Prostate Adenocarcinoma (PCa; 20%). “Off-trial” ICI was more often administered later in the disease course, compared to a more even distribution of “on-trial” ICI administration. Mean PFS and OS for both cohorts can be seen in Table. Conclusions: As seen in our single-institution referral center, the use of immune checkpoint inhibitors has significantly increased – and is now more commonly used off-trial than on-trial. As their use becomes more common, their efficacy in “off-trial” populations must be further investigated. [Table: see text]

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