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Introduction Over the last few years, improved outcomes in patients with chronic lymphocytic leukemia (CLL) have been credited to the introduction of novel agents for its treatment. However, the overall cardiovascular safety profile of these agents has not been studied adequately. Methods We searched the Food and Drug Administration Adverse Event Reporting System (FAERS) database for adverse events reported for several of these novel agents: ibrutinib, acalabrutinib, venetoclax, and idelalisib. Results A total of 6074 cardiac adverse events were identified; ibrutinib (4832/36581; 13.2%) was found to have the highest risk of cardiac adverse events. The frequency of atrial fibrillation was highest (41.5%) in the ibrutinib group, while the idelalisib and acalabrutinib groups had the highest reported frequencies of heart failure (25.1%) and myocardial infarction (13.6%), respectively. Hypertension was noted to be relatively higher in the acalabrutinib (25.6%) and venetoclax (11.8%) groups. Overall reported mortality associated with cardiac events was highest in the venetoclax (29.4%) and idelalisib (27.1%) groups. Conclusion Novel agents in the CLL armamentarium have been associated with several cardiovascular adverse events. Further studies are needed to identify high-risk groups that would benefit from robust cardiovascular surveillance after initiation of treatment with these novel agents.

BackgroundSeveral anti-cancer drugs have been linked to new onset atrial fibrillation (AF) but the true association of these drugs with AF is unknown. The FDA Adverse Event Reporting System (FAERS), a publicly available pharmacovigilance mechanism provided by the FDA, collects adverse event reports from the United States and other countries, thus providing real-world data.ObjectivesTo identify anti-cancer drugs associated with AF using the FAERS database.MethodsThe FAERS database was searched for all drugs reporting AF as an adverse event (AE). The top 30 anti-cancer drugs reporting AF cases were shortlisted and analyzed. Proportional reporting ratio (PRR) was used to measure disproportionality in reporting of adverse events for these drugs.ResultsWhen analyzed for AF as a percentage of all reported AE for a particular drug, Ibrutinib had the highest percentage (5.3%) followed distantly by venetoclax (1.6%), bortezomib (1.6%), carfilzomib (1.5%), and nilotinib (1.4%). The percentage of cardiac AE attributable to AF was also highest for ibrutinib (41.5%), followed by venetoclax (28.4%), pomalidomide (23.9%), bortezomib (18.2%), and lenalidomide (18.2%). Drugs with the highest PRR for AF included ibrutinib (5.96, 95% CI= 5.70–6.23), bortezomib (1.65, 95% CI = 1.52–1.79), venetoclax (1.65, 95% CI = 1.46–1.85), carfilzomib (1.53, 95% CI = 1.33–1.77), and nilotinib (1.46, 95% CI = 1.31–1.63).ConclusionsWhile newer anti-cancer drugs have improved the prognosis in cancer patients, it is important to identify any arrhythmias they may cause early on to prevent increased morbidity and mortality. Prospective studies are needed to better understand the true incidence of new onset AF associated with anti-cancer drugs.

e18076 Background: Mammary analog secretory carcinoma (MASC) is a rare malignant salivary gland tumor of the head and neck region that was first described by Skálová et al. in 2010. It histologically mimics breast secretory carcinoma and parotid acinic cell carcinoma, and characterized by ETV6-NTRK3 fusion gene. This review aims to investigate the clinicopathologic features, treatment, and outcomes of MASC in adults. Methods: PubMed search for MASC adults (18+ years) from data inception through 2021, pooled with a case from our institution. Kaplan-Meier analysis was used to plot survival curves. Results: Of the 254 included cases, female:male ratio 1.02:1 with a mean age at diagnosis (±SD, range) of 50.1 (±16.7, 18–86) years. In terms of location, 143 (56.3%) occurred in the parotid gland, 21 (8.3%) in the submandibular gland, 21 (8.3%) in the lip, 15 (5.9%) in the thyroid gland–all (100%) had a component of classical type papillary carcinoma, 15 (5.9%) were cutaneous, 13 (5.1%) in the buccal mucosa, 12 (4.7%) split between hard and soft palate, 4 (1.6%) in the nasal mucosa, 2 (0.8%) in the lung, and remaining 8 (3.1%) each in the conjunctiva, tongue, minor salivary gland, submaxillary gland, maxillary sinus, ethmoid sinus, upper esophagus, and mandible. Patients mostly presented with swelling or growing mass in 95.4% (out of which, 93.3% were painless), followed by a painful ulcer in 1.8%. Median tumor size was 1.9 cm (range 0.3cm–8.5cm). Median duration of symptoms at time of presentation was 12 (range 1-360) months. Tumors were T1 (49.7%), T2 (23.9%), T3 (20.3%), and T4 (6.1%), N0 (81.9%), N1 (10.7%), N2 (7.4%), M0 (97.4%), and M1 (2.6%). Most patients (70.7%) presented as early stage (I or II) which was associated with a high survival probability based on a log-rank test (p-value: 0.0007). All patients had surgical resection, mostly combined with neck dissection (ND) in11.4%, radiation (RT) in 7.8%, ND+RT in 4.7%, ND with platinum-based chemoradiation in 1.0%, and one case reported use of Crizotinib followed by Entrectinib with disease progression at 4.5 and 7 months, respectively. Among patients with reported outcomes, 92.2% were alive with a median follow-up of 26 (range 1-228) months, and 7.8% deceased with a median time-to-death of 29 (range 1-107) months. Eleven (4.3%) reported a high-grade MASC and 18.5% of patients lived for over five years after their diagnosis. Conclusions: Early stage was a notable predictor of higher survival probability in MASC patients. Its rarity, heterogeneity of clinical behaviors, and variable outcomes make it even more challenging. This review serves as real-world evidence to further our understanding of this rare entity and shed light on prospective clinical trial design.

8550 Background: The PACIFIC study (PS) concluded that the use of durvalumab from 1 to 42 days after concurrent chemoradiotherapy (CXRT) in stage 3 unresectable non-small cell lung cancer (NSCLC) increased the median overall survival (mOS) from 29 to 48 months. It also showed a benefit in tumors with PD-L1 50%. Less than 35% of patients with PD-L1 50% (p-value 0.02). Patients who received durvalumab 30-60 days after concurrent CXRT had a lower OS at 30 months compared to those who started before 30 days (44% versus 90%). However, statistical significance was not reached (p-value 0.45). Conclusions: This study demonstrates that patients with a PD-L1 tumor expression of 50% in this patient population. Time from CXRT to the start of durvalumab was not shown to affect survival outcomes.[Table: see text]

Background Lung cancer cause nearly 1.76 million deaths worldwide in 2018. In 2011, the National-Lung-Cancer-Screening-Trial showed 20% relative risk reduction with LDCT and subsequently led to the current USPSTF screening guidelines. However, the predominant focus on elderly, Caucasian questions its generalizability to communities with young, African Americans such as our institution. Hence, the objective of our study is to investigate the need to modify the current screening guidelines at our institution by assessing the applicability of newer individual risk-based prediction models for LDCT screening. Methods This is a retrospective observational cohort study of newly diagnosed lung cancer patients at LSU Health Sciences Center Shreveport from 2011 to 2015. One-third of the patients did not meet the current USPSTF screening guidelines. We categorized them into high-risk (groups1 and 2), moderate-risk, and low-risk according to 2018 NCCN Lung Cancer Screening Guidelines Version 1.2020. The high-risk groups were differentiated using the Tammemagi lung cancer risk calculator. Results Among those who did not meet the screening guidelines, nearly 50% were African American, 95% with known smoking history, and 80% diagnosed at advanced stage at the time of diagnosis. After employing the Tammemagi Risk based calculator, 12.5% were categorized into high-risk group 2, who are also eligible for annual LDCT. Conclusion The current USPSTF guidelines have failed in our population consisting of young African American smokers, questioning the health disparity in medicine. By employing individual risk-based prediction models, we could potentially identify tailored high-risk populations leading to appropriate use of LDCT screening.

Background: Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Both clinical probability and laboratory testing are needed for establishing a diagnosis of HIT. The 4Ts clinical scoring system, due to a very high negative predictive value when low, offers a robust means to exclude a diagnosis of HIT. However, these strategies are under-employed in clinical practice and limited evidence indicates a high prevalence of over-testing for HIT. Methods: This retrospective analysis was conducted to identify patients who underwent heparin/PF4 antibody testing over a period of 12 months. The testing was performed using an ELISA-based IgG anti-heparin/PF4 antibody assay and an optical density (OD) of 0.4 was used as a cut-off for a positive value. Electronic medical records were reviewed for 4T score documentation, anti-PF4 results, SRA testing and 4T scores were retrospectively calculated for all the patients. SAS v9.4 (Cary, NC) was used for statistical analysis. Results: A total of 105 patients who underwent anti-PF4 antibody testing were included for analysis. Majority of the patients in our cohort were admitted in an intensive care unit setting (75/105,71.4%). On chart review, only 17 patients (16.2%) were noted to have documentation of 4T score. Based on the retrospectively calculated 4T scores, 60 patients (57.1%) had low pre-test probability, 41 (39%) had intermediate pre-test probability and 4 (3.8%) patients were noted to have high pre-test probability. Anti-PF4/heparin antibodies were positive in 9 patients, of which 5 (55.5%) patients did not undergo concomitant SRA testing. Out of 9, 4 (44.4%) had weakly positive (0.4-1.0 OD units), 2 (21.1%) had strongly positive (1.0-2.0 OD units) and 2 (21.1%) patients had very strongly positive (>2 OD units) anti-PF4 antibody titers. Out of 105 patients, SRA was tested in 11 patients (10.5%) and was noted to be positive in 1 (0.95%). Overall, 2 patients were diagnosed and treated for HIT, out of which the diagnosis was not confirmed with SRA in 1 patient (due to high pre-test probability and very strong anti-PF4 titers). In the remaining patients, sepsis (48, 46.6%) and drug-induced thrombocytopenia (29, 28.2%) emerged as the most common possible causes of thrombocytopenia. Conclusion: Among hospitalized patients, over-testing for HIT is common. Practices to promote 4T score documentation and evidence-based anti-PF4 testing may help prevent unnecessary costs associated with serological testing and costly alternate anticoagulants. To improve overall outcomes, clinicians should also attempt to identify and treat other more likely causes of thrombocytopenia, especially in patients with low pre-test probability for HIT. Disclosures No relevant conflicts of interest to declare.

// Ashish D. Dwary 1 , Samip Master 1 , Abhishek Patel 1 , Constance Cole 1 , Richard Mansour 1 , Glenn Mills 1 , Nebu Koshy 1 , Prakash Peddi 1 , Gary Burton 1 , Dalia Hammoud 1 and Kavitha Beedupalli 1 1 Department of Medicine, Division of Hematology-Oncology, Louisiana State University Health Sciences Center, Shreveport, LA, USA Correspondence to: Kavitha Beedupalli, email: // Keywords : excellent response, chemotherapy, immunotherapy Received : June 28, 2017 Accepted : July 26, 2017 Published : August 08, 2017 Abstract Introduction: Immunotherapy in the form of immune checkpoint inhibitors has changed the landscape of cancer treatment. Newer monoclonal antibodies are coming up and are being tested in various cancers during different stages of treatment. With the increasing use of immune checkpoint inhibitors in the management of various types of cancers, the question is raised as to what next can be offered to a patient who has progressed on this newer treatment. Does Sequence matter? There have been reports of improved responses to chemotherapy after immunotherapy in the form of vaccines. Here we present a case series of 6 patients who progressed on immunotherapy with immune checkpoint inhibitors after initial modality of treatment (chemotherapy/radiation), subsequently received chemotherapy with excellent response. Methods: We have a cohort of six patients who had disease progression on second line Immunotherapy for solid or hematological malignancies and had ECOG < 2. All these patients received third line salvage chemotherapy. Three patients had metastatic head and neck cancer, 2 had non-small cell lung cancer (NSCLC), and one had T -cell rich B- cell lymphoma. Prior review and approval were obtained from our institutional review board. Results: All patients had an excellent response to chemotherapy in third line setting, after immune checkpoint inhibitors and most of them achieved a complete response. Conclusion: Targeting cancer with chemotherapy after failure of immunotherapy is a valid option and can lead to better response rates and PFS which may lead to OS. This effect may be secondary to immunotherapy removing the inhibition exerted by tumor cells or other immune cells initially followed by cytotoxic chemotherapy mediated killing of tumor cells.

e18763 Background: Recent single-center, retrospective reviews have evaluated the effect of influenza vaccinations on the incidence and severity of immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICI). Methods and outcomes in these studies vary. The most common medication investigated was ipilimumab, an Anti-CTLA-4 monoclonal antibody. There is limited data evaluating the incidence of irAEs in those receiving the specific ICIs, program death-1 (PD-1) and program death ligand-1 (PD-L1) inhibitors. Methods: A retrospective chart review was conducted including patients 18 to 89 years old who received single-agent pembrolizumab, nivolumab, atezolizumab, or durvalumab at an academic medical center from August 2015 to August 2019. The primary objective was to evaluate the incidence of irAEs in those who received an influenza vaccine compared to those who did not. Electronic health records, and the Louisiana Immunization Network for Kids (LINKS), which now collects adult information, were utilized for data collection. Chi-square tests were used to evaluate all endpoints. Results: Of the 217 charts screened, 133 were included in this study Fifty-three patients were included in the influenza vaccination group and 80 patients in the group that did not receive influenza vaccinations. The median age in those who received an influenza vaccine and in those who did not were 61 years and 62 years, respectively. The most common cancer diagnoses were lung cancer and melanoma. Ninety-one percent of patients in the vaccination group versus 81% in the group who did not receive an influenza vaccine received either nivolumab or pembrolizumab (PD-1 inhibitors). There was no statistical difference in irAEs in those who received an influenza vaccine versus those who did not (30% versus 45%, p = 0.15). The only significant secondary outcome found was the rate of irAEs in patients receiving a PD-1 inhibitor versus a PD-L1 inhibitor regardless of vaccination (42.2% versus 11.1%, p = 0.03). The majority of irAEs were grade 1 or 2. Conclusions: Based on this study, receiving an influenza vaccine does not have an influence on the risk of irAEs in those receiving ICI, specifically PD-1 and PD-L1 inhibitors. These outcomes may have been affected by adherence issues with yearly influenza vaccinations, inaccurate vaccine records, and receiving vaccines out of state. The statistically significant secondary outcome may have been affected by the disproportionate number of patients who were receiving a PD-1 inhibitor in this study. Larger population studies are needed to validate these findings and identify both the risk and benefit of patients receiving their yearly influenza vaccine while receiving ICI.

e13572 Background: Lung cancer is the leading cause of cancer related deaths in men and women with 1.76 million deaths worldwide in 2018 [1]. Given its high prevalence and mortality, trials were developed to improve screening strategies. National-Lung-Screening-Trial showed a 20% relative-risk-reduction in mortality in people screened with annual low-dose-CT-scan [2] leading to the implementation of current USPSTF guidelines. We used USPSTF screening criteria to estimate the proportion of non-small cell lung cancer (NSCLC) patients that would have been screening-eligible at our institution.Upon chart review 33% of overall lung cancer patients at our institution did not meet the screening guidelines. We decided to investigate the need to modify the current screening guidelines of our institution based on individual risk assessment. Methods: We conducted a retrospective observational cohort study of the new diagnoses at Louisiana-State-University-Shreveport from 2011-2015. Patients were categorized into high-risk (groups 1 and 2), moderate risk, and low risk according to 2018 NCCN Lung Cancer Screening Guidelines Version 1.2020 [3]. To differentiate between high-risk group 2 and moderate risk, the Tammemagi lung cancer risk calculator was employed, considering 1.3% threshold of lung cancer risk over 6-year time frame [4]. According to NCCN, high-risk group 1 and 2 are eligible for annual low-dose-CT-scan. Results: 33% of overall lung cancer patients at our institution did not meet the screening guidelines criteria, among the 33% ineligible for screening, only 12.5% fell under the high-risk category based on the Tammemagi calculator. Conclusions: Despite using individual risk assessment based on Tammemagi calculator, 87.5% of lung cancer patients ineligible to current USPSTF guidelines are still missing the eligibility for screening at our institution. We believe more efficient risk prediction models have to be developed to improve selection of individuals for lung cancer screening.