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PurposeCardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers.MethodsRecommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology.ResultsA total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms.RecommendationsIt is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.

e19534 Background: Cardiovascular adverse events (CVAE) are common in patients with multiple myeloma (MM). Recent evidence suggests higher rates of CVAE occur among patients receiving carfilzomib (CFZ) compared to other MM therapies. We sought to determine the real-world relative incidence of CVAE in patients receiving CFZ and bortezomib (BTZ). Methods: We conducted a retrospective cohort study using the Optum Clinformatics Datamart. Patients with MM were included if they received BTZ or CFZ from 2012 to 2016. Exposure periods were defined as 90 days following infusion of either drug. Cardiac hospitalizations were identified using validated ICD-9 or ICD-10 code algorithms for heart failure, arrhythmia, myocardial infarction, and hypertensive urgency. Incidence rate ratios (IRR) were calculated using Poisson regression. Results: We identified 922 patients receiving CFZ and 4092 patients receiving BTZ (median age 70 and 72; median treatment duration 99 and 107 days; concurrent immunomodulatory drugs received in 28% and 25%, respectively). Unadjusted CVAE rates are summarized below. A multivariable regression model showed age (IRR 1.43, 95% CI 1.33-1.55) and male gender (IRR 1.22, 95% CI 1.07-1.40) were independent risk factors for CVAE while concurrent IMiD prescription was associated with lower risk (IRR 0.70, 95% CI 0.58-0.85). Adjusted CVAE rates were similar for patients treated with CFZ and BTZ (IRR 1.06, 95% CI 0.89-1.27). Conclusions: We found higher rates of CVAE hospitalizations than described in clinical trials. This may reflect differences in real-world treatment, patient selection patterns, or later identification of CVAE. Further study is need to identify patients at high-risk of CVAE and to develop risk reduction strategies. [Table: see text]

PurposeTo review the evidence on the incidence of long-term cardiac or pulmonary toxicity secondary to chemotherapy, radiotherapy, or trastuzumab in symptomatic and asymptomatic cancer survivors.MethodsAn American Society of Clinical Oncology Panel reviewed pertinent information from the literature through February 2006.ResultsFew studies directly addressing the benefits of screening for long-term cardiac or pulmonary toxicity in asymptomatic cancer survivors who received chemotherapy, radiotherapy, or trastuzumab were identified. The reviewed literature included primarily retrospective and cross-sectional studies describing the incidence of cardiac and pulmonary late effects. Anatomic and/or functional abnormalities have been associated with use of all currently available anthracyclines and their derivatives. Trastuzumab-related cardiac dysfunction rarely causes death, and in most cases is reversible with improvement in cardiac function on drug discontinuation and/or treatment with cardiac medications. The estimated aggregate incidence of radiation-induced cardiac disease is 10% to 30% by 5 to 10 years post-treatment, although the incidence may be lower with modern techniques. Radiation pneumonitis is reported in 5% to 15% of lung cancer patients receiving definitive external-beam radiation therapy. A minority of patients may develop progressive pulmonary fibrosis; late complications include cor pulmonale and respiratory failure. Bleomycin-induced pneumonitis is an acute rather than late effect of treatment. Late pulmonary complications in bone marrow or stem cell transplantation patients who develop interstitial pneumonitis include idiopathic pneumonia syndrome and bronchiolitis obliterans.ConclusionAn increased incidence of cardiac and/or pulmonary dysfunction is observed in cancer survivors. Research is needed to identify high-risk patients, and to determine the optimal screening strategies and subsequent treatment.

8018 Background: The incidence and nature of cardiovascular adverse events (CVAEs) with carfilzomib (CFZ) in multiple myeloma (MM) remain incompletely defined. We performed the first systematic review and meta-analysis of CFZ CVAEs. Methods: PubMed was queried for the keywords “carfilzomib,” “Kyprolis,” and “PX-171.” Phase 1-3 clinical trials of carfilzomib in MM with evaluable toxicity data were included. CVAEs were defined as heart failure, hypertension, ischemia, and arrhythmia. All-grade and grade ≥3 CVAEs and study characteristics were recorded. Summary incidence rates and relative risks (for randomized trials) with 95% confidence intervals were calculated using the logistic-normal random-effects model. Subgroup analyses were performed using study level covariates. Results: 514 studies were reviewed. 2623 MM patients from 25 eligible studies were included. Incidence rates are summarized in the table. All grade and grade ≥3 CVAEs were seen in 16.8% and 7.6 %, respectively. Phase 2 or 3 studies, carfilzomib doses ≥45mg/m2, and longer infusion length were study characteristics associated with high-grade cardiac AEs (p65, prior MM therapies, and concurrent MM therapies were not associated with CVAEs (p>.05). For the three randomized trials, the relative risk of all-grade and grade ≥3 CVAEs were 1.75 and 2.25, respectively (p

7525 Background: Cardiovascular (CV) complications associated with ibrutinib (Ibr) include hypertension (HTN) and atrial fibrillation (AFIB) (incidence 26% and 9%, OBrien, ASH 2016). Unlike clinical trials, Ibr toxicities are the most common reasons for its discontinuation in clinical practice. The incidence of HTN in pts treated with Ibr outside of clinical trial setting and its impact on outcomes is unknown. Methods: Retrospective, cohort study of Ibr-treated CLL pts to estimate HTN incidence. Baseline CLL characteristics and co-morbidities were recorded. Blood pressure (BP) measurements were recorded prior to Ibr and sequentially following exposure at specific time points. CV meds were reviewed during a 12 mo follow-up period. The association between Ibr exposure and BP was tested. Results: 153 consecutive CLL pts treated with Ibr at a dose of 420 mg/day were identified. Med age was 57 yr (range: 34-87), relapsed CLL (69%), follow-up 14.5 mo. CV pre-Ibr characteristics included: smoking hx (49%), HTN (42%), hyperlipidemia (39%), diabetes (17%), CAD (12%), AFIB (6.8%). Proportion of pts on ≥1 anti-HTN med increased from 44% pre-Ibr (20% ≥ 2) to 57% during Ibr (30% ≥ 2). Med pre-Ibr BP was 127/70 mmHg (range 90-182/48-95mmHg). At 1, 3, 6, 9, 12 mo, med BPs were 137/73, 141/75, 143/76, 140/75, 142/77 (7 mo to peak BP). There was a significant association between Ibr exposure and increased BP (p

9624 Background: Anthracyclines are highly effective as anticancer therapies and have led to important survival gains. There are, however, significant concerns over cardiotoxicity. The overall obje...

9644 Background: Anthracyclines (ANTH) are widely used as cancer therapies but carry a significant risk of heart failure (HF) and left ventricular dysfunction (LVD). Improved cardiovascular (CV) ri...

TO THE EDITOR: We read with interest the article by Nowakowski et al concerning statin use and prognosis in patients with lymphoma treated in the rituximab era. As a result of the work of Winiarska et al and correspondence with Rabinowitz, we reviewed our recent experience at the Abramson Cancer Center of the University of Pennsylvania (Philadelphia, PA) in a similar cohort of patients. After approval by the institutional review board, we examined the medical records of 108 patients with non-Hodgkin’s lymphoma who were treated with rituximab. The primary end point was clinical response 1 year after therapy completion. Response was defined according to standard definitions. We used 2 analysis to compare the proportions of complete responders, partial responders, and nonresponders in the statin group with those in the nonstatin group. We found no significant difference in these proportions between the two groups. According to our analysis, the proportion of complete responders in the statin group was 0.7 versus 0.662 in the nonstatin group (P .75; 95% CI, 0.760 to 1.470). Additional analysis revealed no relationship between type of statin, dose used, or duration of therapy before start of chemotherapy. Our findings are consistent with those of Nowakowski et al and represent additional evidence that the concurrent use of statins in the clinical setting during treatment of patients with lymphoma does not adversely affect outcome.

4592 Background: Testicular cancer survivors (TCS) who receive cisplatin-based chemotherapy (CBCT) are reported to have an increased risk of coronary heart disease (CHD) compared to chemo-naive TCS (J Clin Oncol 21:1513–1523, 2003). We hypothesized that TCS treated with CBCT would demonstrate abnormal objective measures of future CHD risk compared to chemo-naive TCS. Methods: TCS ≥ 2 years from diagnosis underwent evaluation using established objective measures predictive of future CHD risk: body mass index (BMI), Framingham relative risk (RR), flow-mediated endothelium-dependent vasodilation of the brachial artery (FMD), carotid artery intima-media thickness (IMT), serum intercellular adhesion molecule-1 (ICAM-1), and high sensitivity C-reactive protein (hs-CRP). Data were analyzed using parametric and non-parametric statistics as appropriate. Results: 30 TCS who received CBCT and 20 chemo-naive TCS were recruited. The mean age and time from diagnosis were similar between the 2 groups. Both groups demonstrated elevated BMI, increased Framingham RR, and impaired FMD, consistent with an increased risk of CHD. However, there were no statistically significant differences in these measures between the two groups. Carotid IMT, ICAM-1, and hs-CRP were not significantly abnormal and these measures also did not differ between the two groups. Conclusions: TCS demonstrate abnormal objective measures of CHD risk in both CBCT-treated and chemo-naive groups. These data suggest that behavioral interventions to modify CHD risk should target all TCS independent of chemotherapy status. All values reported are mean ± standard deviation [Table: see text] No significant financial relationships to disclose.

8163 Background: Studies suggest that TC survivors treated with cisplatin-based chemotherapy (CBCT) have increased cardiovascular risk (Meinardi, et al. J Clin Oncol, 2000; Huddart, et al. J Clin Oncol, 2003). Detection of SA in asymptomatic individuals could identify an at risk cohort for targeting behavioral and/or pharmacologic interventions. SA can be detected by measuring flow-mediated brachial artery vasodilatation (FMD), carotid artery intima-media thickness (IMT), and biochemical markers including ICAM and hsCRP. Methods: In this pilot study, we compared TC survivors who received CBCT with those who are chemo-naive (CN) with respect to Framingham risk scores, brachial artery FMD, carotid artery IMT, and ICAM/hsCRP. Results: To date, 27 subjects have been enrolled: 16 received CBCT, 11 were CN. Median age of the CBCT subgroup is 41 years vs. 43 years for the CN subgroup. Both groups are approximately 6 years post-diagnosis. Both subgroups have an increased 10-year coronary heart disease risk compar...