Long-term outcomes in patients with chronic lymphocytic leukemia treated with ibrutinib: Focus on hypertension and cardiovascular toxicity.

BACKGROUND: Continuous ibrutinib administration is needed to maintain efficacy in patients with chronic lymphocytic leukemia (CLL) and, as such, long-term toxicity is a concern. The authors report the 5-year follow-up of patients with CLL who received treatment with ibrutinib with a focus on hypertension and cardiovascular toxicities. METHODS: Patient characteristics were assessed, including blood pressure, cardiovascular disease, disease progression, and death. Univariate logistic regression analysis assessed the relation of patient characteristics and the development of new or worsened hypertension. The incidence of hypertensive outcomes was evaluated using competing risk. Survival was estimated using the Kaplan-Meier method. RESULTS: Three hundred patients with CLL who were treated with ibrutinib on clinical trials were included. The median patient age at study enrollment was 65 years (range, 29-83 years). Seventy percent of patients were men, and 88% were Caucasian. Sixty-nine percent of patients had hypertension at baseline, and 47% were on antihypertensive medication. Eighty-eight percent had relapsed or refractory CLL. New-onset and worsening hypertension were common, occurring in 68.5% and 38% of patients, respectively. Systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg was observed in 16.9% of patients. Hypertension was reversible after ibrutinib discontinuation. Older age, male sex, tobacco use, and chronic kidney disease were associated with ibrutinib-related hypertension. Baseline hypertension was not associated with major adverse cardiovascular events in ibrutinib-treated patients nor with event-free or overall survival. CONCLUSIONS: Hypertension is a common toxicity in patients with CLL who receive ibrutinib but is manageable in most patients. Other than chronic kidney disease, baseline cardiovascular disease did not affect ibrutinib-related hypertension nor was hypertension associated with major adverse cardiovascular events or survival. PLAIN LANGUAGE SUMMARY: Ibrutinib is an effective treatment for patients with chronic lymphocytic leukemia. Ibrutinib is a well tolerated therapy, however hypertension can develop or worsen in patients receiving ibrutinib and other cardiovascular events are significant challenges to the use of this drug. This may be particularly true in patients with heart disease. Short-term side effects may worsen heart disease, but the long-term impact is unknown. The long-term results of ibrutinib on heart disease and hypertension are described.

Reclassification of Treatment Strategy with Fractional Flow Reserve in Cancer Patients with Coronary Artery Disease.

Background and Objectives: Cancer and coronary artery disease (CAD) often coexist. Compared to quantitative coronary angiography (QCA), fractional flow reserve (FFR) has emerged as a more reliable method of identifying significant coronary stenoses. We aimed to assess the specific management, safety and outcomes of FFR-guided percutaneous coronary intervention (PCI) in cancer patients with stable CAD. Materials and Methods: FFR was used to assess cancer patients that underwent coronary angiography for stable CAD between September 2008 and May 2016, and were found to have ≥50% stenosis by QCA. Patients with lesions with an FFR > 0.75 received medical therapy alone, while those with FFR ≤ 0.75 were revascularized. Procedure-related complications, all-cause mortality, nonfatal myocardial infarction, or urgent revascularizations were analyzed. Results: Fifty-seven patients with stable CAD underwent FFR on 57 lesions. Out of 31 patients with ≥70% stenosis as measured by QCA, 14 (45.1%) had an FFR ≥ 0.75 and lesions were reclassified as moderate and did not receive PCI nor DAPT. Out of 26 patients with <70% stenosis as measured by QCA, 6 (23%) had an FFR < 0.75 and were reclassified as severe and were treated with PCI and associated DAPT. No periprocedural complications, urgent revascularization, acute coronary syndromes, or cardiovascular deaths were noted. There was a 22.8% mortality at 1 year, all cancer related. Patients who received a stent by FFR assessment showed a significant association with decreased risk of all-cause death (HR: 0.37, 95% CI 0.15−0.90, p = 0.03). Conclusions: Further studies are needed to define the optimal therapeutic approach for cancer patients with CAD. Using an FFR cut-off point of 0.75 to guide PCI translates into fewer interventions and can facilitate cancer care. There was an overall reduction in mortality in patients that received a stent, suggesting increased resilience to cancer therapy and progression.

Immune Checkpoint Inhibitor (ICI)-Related Cardiotoxicity.

The growing success of immune checkpoint inhibitors (ICIs) has led to improved outcomes in several types of cancers with studies looking for expanding their indications and use. However immune-related adverse events have been recognized of which myocarditis is associated with a high mortality. Other cardiac events such as arrhythmias, pericardial disease, and coronary atherosclerosis have been observed in patients on ICI therapy. These cardiac toxicities are thought to be the result of increased inflammatory responses after inhibition of specific checkpoint proteins on T cells. Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant myocarditis, hemodynamic instability, and cardiac arrest. We will review the most commonly reported cardiovascular toxicities associated with ICIs and their management.

Immune Checkpoint Inhibitors (ICIs)-Related Cardiotoxicity.

The growing success of immune checkpoint inhibitors (ICIs) has led to effectively treating several types of cancers. Even though their use has been associated with the development of cardiac adverse effects, which may decrease the overall survival in cancer patients. These cardiac toxicities are thought to be the result of targeting specific checkpoint proteins on normal myocardial cells leading to over stimulation of the immune system as well as secondary downstream off-target effects on normal tissue.Although cardiotoxicities related to immunotherapy are reportedly rare, they can be severe and associated with life-threatening conditions such as fulminant myocarditis, hemodynamic instability, and cardiac arrest.We will review the most commonly reported cardiovascular toxicities associated with ICIs and their management.

Cardiac toxicities of anticancer treatments: chemotherapy, targeted therapy and immunotherapy.

PURPOSE OF REVIEW: Current oncologic treatments have shown improvement in overall survival in cancer patients. However, the cardiac toxicities of cancer therapeutics, particularly chemotherapy, targeted therapy and immunotherapy can have life-threatening side effects. RECENT FINDINGS: A MEDLINE search for cardiovascular toxicities associated with Federal Drug Administration (FDA)-approved cancer treatments including chemotherapy, targeted therapy and immunotherapy was performed. We included comprehensive articles and research articles establishing the incidence, diagnosis, monitoring and management of cardiovascular toxicities related to cancer treatments until January 2019.This review highlights the mechanisms and epidemiology of cardiotoxicity associated with some cancer treatments. The most common cardiovascular side-effects are discussed at an introductory level with emphasis on those related with the development of heart failure. SUMMARY: Cardiovascular side effects of cancer treatments are common and might affect the survival in cancer patients. Recognition and management of these side effects require understanding of their mechanisms and their clinical manifestations. A multidisciplinary approach with understanding of both the cardiovascular and oncologic risks is necessary in order to provide well tolerated and effective cardio-oncology care.

Management of CAD in Patients with Active Cancer: the Interventional Cardiologists' Perspective.

PURPOSE OF REVIEW: Coronary artery disease in patients with active cancer presents particular challenges for clinicians, as optimum management is required in order to treat the underlying malignancy and to reduce morbidity and mortality associated with cardiovascular diseases. Special considerations must be made in respect to either primary or secondary thrombocytopenia, the presence of coagulopathies and the propensity of bleeding, vascular access complications, and increased risk of stent thrombosis. RECENT FINDINGS: In presence of acute coronary symptoms, the cardio-oncology team has to make a complex decision between conservative medical management or early angiography (within 24 h) and revascularization. There is a lack of reliable data on the outcomes of patients with active cancer who undergo invasive procedures for the diagnostic and treatment of coronary artery disease. Cardiac catheterization recommendations in cancer patients are being currently elaborated by cardio-oncologists in order to improve the overall survival in cancer patients with coronary artery disease.

Long-term evaluation of cardiac and vascular toxicity in patients with Philadelphia chromosome-positive leukemias treated with bosutinib.

Vascular and cardiac safety during tyrosine kinase inhibitor (TKI) therapy is an emerging issue. We evaluated vascular/cardiac toxicities associated with long-term bosutinib treatment for Philadelphia chromosome-positive (Ph+) leukemia based on treatment-emergent adverse events (TEAEs) and changes in QTc intervals and ejection fraction in two studies: a phase 1/2 study of second-/third-/fourth-line bosutinib for Ph+ leukemia resistant/intolerant to prior TKIs (N = 570) and a phase 3 study of first-line bosutinib (n = 248) versus imatinib (n = 251) in chronic phase chronic myeloid leukemia. Follow-up time was ≥48 months (both studies). Incidences of vascular/cardiac TEAEs in bosutinib-treated patients were 7%/10% overall with similar incidences observed with first-line bosutinib (5%/8%) and imatinib (4%/6%). Few patients had grade ≥3 vascular/cardiac events (4%/4%) and no individual TEAE occurred in >2% of bosutinib patients. Exposure-adjusted vascular/cardiac TEAE rates (patients with events/patient-year) were low for second-line or later bosutinib (0.037/0.050) and not significantly different between first-line bosutinib (0.015/0.024) and imatinib (0.011/0.017; P ≥ 0.267). Vascular/cardiac events were managed mainly with concomitant medications (39%/44%), bosutinib treatment interruptions (18%/21%), or dose reductions (4%/8%); discontinuations due to these events were rare (0.7%/1.0%). Based on logistic regression modelling, performance status >0 and history of vascular or cardiac disorders were prognostic of vascular/cardiac events in relapsed/refractory patients; hyperlipidemia/hypercholesterolemia and older age were prognostic of cardiac events. In newly diagnosed patients, older age was prognostic of vascular/cardiac events; history of diabetes was prognostic of vascular events. Incidences of vascular and cardiac events were low with bosutinib in the first-line and relapsed/refractory settings following long-term treatment in patients with Ph+ leukemia. Am. J. Hematol. 91:606-616, 2016. © 2016 Wiley Periodicals, Inc.

Coronary artery disease detected by coronary computed tomography angiography in adult survivors of childhood Hodgkin lymphoma.

BACKGROUND: Survivors of Hodgkin lymphoma (HL) have significant cardiovascular risk and require long-term surveillance. The current study assessed the prevalence of coronary artery disease (CAD) by coronary computed tomography angiography (CCTA) in adult survivors of childhood HL. METHODS: Thirty-one survivors of HL, 13 of whom (42%) were treated with radiotherapy (RT) only and 18 of whom (58%) were treated with multimodal therapy, underwent CCTA, echocardiography, electrocardiography (ECG), and treadmill stress testing. Obstructive CAD was defined as ≥50% occlusion of the left main or ≥70% occlusion of the left anterior descending, left circumflex, or right coronary arteries on CCTA. Echocardiograms with resting wall motion abnormalities or an ejection fraction <50%; ECGs with Q waves, ST abnormalities without Q waves, or T-wave abnormalities without Q waves; and a J-point depression of ≥1 mm with a horizontal or downsloping ST segment on stress testing were considered abnormal. RESULTS: The prevalence of disease in participants (median age, 40 years [range, 26 years-55 years]; median time from cancer diagnosis, 24 years [range, 17 years-39 years]) was 39%, with 39 plaques detected among 12 survivors. Three participants (10%) treated with RT only had 4 obstructive lesions; 9 patients (29%; 5 of whom were treated with RT only and 4 of whom were treated with multimodal therapy) had nonobstructive lesions. Approximately 15% of lesions involved the left main, 21% involved the proximal left anterior descending, 18% involved the proximal right coronary, and 13% involved the proximal left circumflex arteries. Of the 12 participants found to have CAD by CCTA, 7 had a positive ECG, 1 had a positive echocardiogram, and 1 had a positive stress test. CONCLUSIONS: CCTA identified CAD in a substantial percentage of survivors of HL and may be an effective screening modality for this population.

Evaluation of a novel blood pressure scoring method and its association with clinical response in cancer patients treated with anti-vascular endothelial growth factor therapy.

BACKGROUND: The purposes of this study were to establish a novel blood pressure (BP) scoring method and to correlate it with clinical response in advanced cancer patients treated with anti-vascular endothelial growth factor (VEGF) therapies. METHODS: We retrospectively analyzed data for 368 patients from 23 clinical trials that included at least one anti-VEGF agent. We determined BP scores using the traditional Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and our novel method that considers both BP readings and number of anti-hypertensive medications the patient received. BP scores were categorized at baseline and four months. Logistic regression analysis correlated elevated scores with clinical response. Agreement between the CTCAE and the new method was assessed. RESULTS: Under the new BP scoring method, partial response rates were 20 % in patients with an elevated score at four months versus 6 % in patients without elevated score (P < 0.001). When adjusted for tumor type, age, sex, history of anti-VEGF treatment, and number of anti-VEGF treatments, elevated BP under the new scoring method had an odds ratio of 3.8 (95 % confidence interval [CI]: 1.8, 8.2; P < 0.001). The kappa statistic for agreement between the CTCAE and new scoring methods was 0.57 (95 % CI: 0.47, 0.67; P < 0.001), indicating significant concordance. CONCLUSION: Using the novel scoring method, an increase in BP scores was a marker for favorable clinical response in patients who received anti-VEGF treatment. This new method ultimately provides information with regard to clinical tumor response over and above that provided by the CTCAE scoring method.

Endobronchial ultrasound: A novel screening test for pulmonary hypertension prior to major pulmonary surgery.

Objectives: Pulmonary hypertension (PH) is an important physiologic variable in the assessment of patients undergoing major thoracic operations but all too often neglected because of the need for right heart catheterization (RHC) due to the inaccuracy of transthoracic echocardiography. Patients with lung cancer often require endobronchial ultrasound (EBUS) as part of the staging of the cancer. We sought to investigate whether EBUS can be used to screen these patients for PH. Methods: Patients undergoing a major thoracic operation requiring EBUS for staging were included prospectively in the study. All patients had also a RHC (gold standard). We aimed to compare the pulmonary artery pressure measurements by EBUS with the RHC values. Results: A total of 20 patients were enrolled in the study. The prevalence of abnormal pulmonary artery pressure was 65% based on RHC. All patients underwent measurement of the pulmonary vascular acceleration time (PVAT) by EBUS with no adverse events. Linear regression analysis comparing PVAT and RHC showed a correlation (r = -0.059, -0.010 to -0.018, P = .007). A receiver operator characteristic curve (area under the curve = 0.736) was used to find the optimal PVAT threshold (140 milliseconds) to predict PH; this was used to calculate a positive and negative likelihood ratio following a positive diagnosis of 2.154 and 0.538, respectively. Conclusions: EBUS interrogation of pulmonary artery hemodynamic is safe and feasible. EBUS may be used as a screening test for PH in high-risk individuals.

Cardiotoxicity of the cancer therapeutic agent imatinib mesylate.

Imatinib mesylate (Gleevec) is a small-molecule inhibitor of the fusion protein Bcr-Abl, the causal agent in chronic myelogenous leukemia. Here we report ten individuals who developed severe congestive heart failure while on imatinib and we show that imatinib-treated mice develop left ventricular contractile dysfunction. Transmission electron micrographs from humans and mice treated with imatinib show mitochondrial abnormalities and accumulation of membrane whorls in both vacuoles and the sarco- (endo-) plasmic reticulum, findings suggestive of a toxic myopathy. With imatinib treatment, cardiomyocytes in culture show activation of the endoplasmic reticulum (ER) stress response, collapse of the mitochondrial membrane potential, release of cytochrome c into the cytosol, reduction in cellular ATP content and cell death. Retroviral gene transfer of an imatinib-resistant mutant of c-Abl, alleviation of ER stress or inhibition of Jun amino-terminal kinases, which are activated as a consequence of ER stress, largely rescues cardiomyocytes from imatinib-induced death. Thus, cardiotoxicity is an unanticipated side effect of inhibition of c-Abl by imatinib.

COVID-19 severity and cardiovascular outcomes in SARS-CoV-2-infected patients with cancer and cardiovascular disease.

Background: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. Objectives: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. Methods: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated. Results: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p<0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31-1.74] vs. OR 1.04 [95% CI 0.90-1.20], pinteraction <0.001). Conclusions: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701).

Evaluation of contemporary echocardiographic and histomorphology parameters in predicting mortality in patients with endomyocardial biopsy-proven cardiac AL amyloidosis.

Introduction: This study examined the role of echocardiographic and cardiac histomorphology parameters in predicting mortality in patients with cardiac AL amyloidosis. Methods: Patients with endomyocardial biopsy-proven cardiac AL amyloidosis treated at MD Anderson Cancer Center between 6/2011 and 6/2020 were identified. Stored echocardiographic images and endomyocardial biopsy samples were processed for myocardial strain analysis and a detailed histomorphology characterization. Results: Of 43 patients; 44% were women and 63% white. Median age was 65 years; 51% underwent stem cell transplantation (SCT). Thirty patients (70%) died during follow up (median follow up: 4.1 years). Lower LA strain (<13.5%) and absence of SCT as a time-varying covariate were significantly associated with increased risk of death in the multivariate cox regression analysis. Higher LV mass and lower RV tricuspid annular plane systolic excursion were associated with increased odds of having ≥5% interstitial amyloid deposition on biopsy in the multivariate logistic regression analysis. Conclusion: Lower LA strain independently predicted mortality in our cohort, and its performance in the routine assessment of AL amyloidosis may be beneficial. Furthermore, SCT for cardiac AL amyloidosis was associated with improved OS. These findings need to be confirmed by larger studies in the era of contemporary systemic therapies.

Management and outcomes of severe aortic stenosis in cancer patients.

BACKGROUND: Aortic stenosis (AS) is the commonest native valve lesion, affecting 43% of all patients with valvular heart disease. The optimal treatment of severe AS in cancer patients is unknown. The purpose of this study was to assess the impact of aortic valve replacement (AVR) on survival of cancer patients with severe AS. METHODS: Cancer patients with severe AS seen at our center between January 2001 and April 2007 were identified. Baseline demographics, symptoms, cancer diagnosis, laboratory data, treatment, and outcome were collected. Patient who had AVR were matched with controls who did not have AS. RESULTS: Out of 39,071 echocardiograms performed over the study period, 1,299 had AS (3.3%), of which 50 patients (0.13%) were identified as having severe AS. Thirteen patients (27%) underwent AVR, and 35 were managed medically. Two patients underwent valvuloplasty and were excluded. Survival was significantly longer in patients with severe AS who underwent AVR and was independent of cancer status or presence of metastases. No difference in survival was found between patients who underwent AVR and matched cancer controls. In a multivariable Cox proportional hazard regression analysis, AVR was the only significant predictor of longer survival (adjusted hazard ratio = 0.22, P = .028). CONCLUSIONS: Cancer patients with severe AS who underwent AVR had an improved survival, regardless of cancer status.

Ibrutinib-Associated Cardiovascular Events in a Patient Wearing an Implanted Loop Recorder.

Ibrutinib is a well-tolerated and effective therapy used for the treatment of chronic lymphocytic leukemia (CLL). However, its use has been associated with cardiovascular events such as atrial fibrillation (Afib), hypertension, and ventricular arrhythmias. Cardiac arrhythmias represent a significant cause of morbidity and mortality. Implanted loop recorders have been integrated into our clinical practice and have been considered a useful tool in guiding the management of patients with cardiac arrhythmias. We report a case that describes our experience on a patient diagnosed with CLL treated with ibrutinib.

A Rare Case of Testicular Teratoma Metastasizing to the Right Ventricle.

We describe a case of testicular teratoma with metastasis to the right ventricle. The mass nearly completely resolved with chemotherapy, obviating the need for upfront surgery. We review the workup of intracardiac metastatic tumors. (Level of Difficulty: Intermediate.).

Clinical Impact of Cardiovascular Magnetic Resonance in Cancer Patients With Suspected Cardiomyopathy.

Objectives: To assess the clinical impact of Cardiovascular Magnetic Resonance (CMR) in clinical decision making of cancer patients with a suspected cardiomyopathy in a tertiary cancer center. Background: Cardiomyopathies of diverse etiologies are frequently encountered in a Cardio-Oncology practice. The clinical impact of CMR after a presumptive diagnosis of cardiomyopathy has not been studied in cancer patients. Methods: We reviewed data on cancer patients with presumptive diagnosis of cardiomyopathy who underwent CMR in a tertiary cancer center. The clinical impact of CMR was defined as either change in clinical diagnosis or management post CMR results. Univariate and multivariate logistic regression models were used to assess whether any of the baseline characteristics were predictive of the clinical impact of CMR. Results: A total of 110 consecutive patients were identified. Clinical impact of CMR was seen in 68 (62%) patients. Change in the clinical diagnosis and management was seen in 56 (51%) and 41 (37%) of patients, respectively. The most common change was prevention of endomyocardial biopsy in 26 patients (24%). Overall, patients with higher left ventricular ejection fraction (LVEF) by echocardiography (echo), clinical impact was influenced more by CMR (LVEF of 37.2 ± 12.3% vs. 51.5 ± 11.6%, p < 0.001). Cancer diagnosis of multiple myeloma was associated with change in the management post CMR (adjusted OR of 25.6, 95% CI 4.0-162.4, p = 0.001). Suspicion of infiltrative cardiomyopathy was associated with a higher likelihood of change in diagnosis. Having an LVEF≥40 by echo was associated with change in diagnosis and management by CMR. Conclusions: Utilization of CMR has a significant clinical impact in cancer patients with suspected cardiomyopathy. Patients with cancer diagnosis of multiple myeloma, suspicion of infiltrative cardiomyopathy and those with higher LVEF by echo seem to benefit more from CMR.

QT Prolongation in Cancer Patients.

Background: QT prolongation and torsades de pointes pose a major concern for cardiologists and oncologists. Although cancer patients are suspected to have prolonged QT intervals, this has not been investigated in a large population. The purpose of this study was to analyze the QT interval distribution in a cancer population and compare it to a non-cancer population in the same institution. Methods: The study was a retrospective review of 82,410 ECGs performed in cancer patients (51.8% women and 48.2% men) and 775 ECGs performed in normal stem cell donors (47.9% women and 52.1% men) from January 2009 to December 2013 at the University of Texas MD Anderson Cancer Center. Pharmacy prescription data was also collected and analyzed during the same time period. Correction of the QT interval for the heart rate was performed using the Bazett and Fridericia formulas. Results: After QT correction for heart rate by the Fridericia formula (QTcF), the mean and 99% percentile QTc for cancer patients were 414 and 473 ms, respectively. These were significantly longer than the normal stem cell donors, 407 and 458 ms, p < 0.001, respectively. Among the cancer patients, the QTc was longer in the inpatient setting when compared to both outpatient and emergency center areas. The most commonly prescribed QT prolonging medications identified were ondansetron and methadone. Conclusion: Our study demonstrates significantly longer QTc intervals in cancer patients, especially in the inpatient setting. Frequently prescribed QT prolonging medications such as antiemetics and analgesics may have a causative role in QT prolongation seen in our cancer hospital.

Cardiovascular Family History Increases Risk for Late-Onset Adverse Cardiovascular Outcomes in Childhood Cancer Survivors: A St. Jude Lifetime Cohort Report.

BACKGROUND: Survivors of childhood cancer have an increased risk of therapy-related cardiovascular disease. It is not known whether family history of cardiovascular disease further increases risk of adverse cardiovascular outcomes among survivors. METHODS: Family history of cardiovascular disease was collected from 1,260 survivors [median age at diagnosis, 8 years (range, 0-23); age at last follow-up, 35 years (range, 18-66)] of childhood cancer in the St. Jude Lifetime Cohort Study. Multivariable risk models evaluated associations with cardiovascular disease (Common Terminology Criteria for Adverse Events grade 2-4 events) and cardiovascular risk factors. RESULTS: Among survivors exposed to chest-directed radiation and/or anthracycline chemotherapy (n = 824), 7% reported a first-degree family history of heart failure, 19% myocardial infarction, 11% stroke, 26% atherosclerotic disease (myocardial infarction and/or stroke), 62% hypertension, and 31% diabetes mellitus. Eighteen percent of exposed survivors developed heart failure, 9% myocardial infarction, 3% stroke, 11% atherosclerotic disease, 30% hypertension, and 9% diabetes mellitus. Having a first-degree family history of atherosclerotic disease was independently associated with development of treatment-related heart failure [RR, 1.38; 95% confidence interval (CI), 1.01-1.88; P = 0.04] among exposed survivors. Risk for hypertension was increased among exposed survivors with a first-degree family history of hypertension (RR, 1.55; 95% CI, 1.26-1.92; P < 0.0001) or of any cardiovascular disease [myocardial infarction, stroke, or heart failure (RR, 1.30; 95% CI, 1.06-1.59; P = 0.01)]. CONCLUSIONS: Family history of cardiovascular disease and cardiovascular risk factors independently increased risk of heart failure and hypertension among survivors of childhood cancer exposed to cardiotoxic therapies. IMPACT: These data show the importance of cardiovascular family history as a risk factor for cardiovascular disease in survivors of childhood cancer.

Case Discussion and Literature Review: Cancer Immunotherapy, Severe Immune-Related Adverse Events, Multi-Inflammatory Syndrome, and Severe Acute Respiratory Syndrome Coronavirus 2.

Pediatric, adolescent and young adult (AYA) patients receiving novel cancer immunotherapies may develop associated toxicities with overlapping signs and symptoms that are not always easily distinguished from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/clinical sequelae. We describe 2 diagnostically challenging cases of SARS-CoV-2 and Multi-Inflammatory Syndrome-Adult (MIS-A), in patients with a history of acute lymphoblastic leukemia following cellular therapy administration and review evolving characterization of both the natural course of SARS-CoV-2 infection and toxicities experienced in younger cancer immunotherapy patients. Vigilant monitoring for unique presentations and epidemiologic surveillance to promptly detect changes in incidence of either condition may be warranted.