Survival in Patients With De Novo Metastatic Prostate Cancer.

This cross-sectional study investigates trends in overall survival among patients with newly diagnosed metastatic prostate cancer in 2 national registries in the United States.

The Association of Agent Orange Exposure with the progression of monoclonal gammopathy of undetermined significance to multiple myeloma: a population-based study of Vietnam War Era Veterans.

Herbicide and pesticide exposure [e.g., agent orange (AO)] is associated with an increased risk of multiple myeloma (MM) due to the contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, it is unclear whether TCDD/AO exposure (AO exposure hereafter) increases the risk of progression of monoclonal gammopathy of undetermined significance (MGUS) to MM. We sought to evaluate the association in a nationwide study of US Veterans. A natural language processing algorithm was used to confirm MGUS and progression to MM. We included Veterans who were diagnosed with MGUS from 10/1/1999 to 12/31/2021 and served during the Vietnam War Era from 1/9/1962 to 5/7/1975. AO exposure was stratified according to three TCDD exposure levels: high (1/9/1962-11/30/1965), medium (12/1/1965-12/31/1970), or low (1/1/1971-5/7/1975). The association between AO exposure and progression was analyzed using multivariable Fine-Gray subdistribution hazard model with death as a competing event. The analytic cohort included 10,847 Veterans with MGUS, of whom 26.3% had AO exposure and 7.4% progressed to MM over a median follow-up of 5.2 years. In multivariable analysis, high exposure was associated with an increased progression rate (multivariable-adjusted hazard ratio 1.48; 95% confidence interval 1.02-2.16), compared to Veterans with no exposure. This information is critical to inform progression risk in patients diagnosed with MGUS and prior AO exposure. It is also applicable to MGUS patients with occupational TCDD exposure from herbicides and pesticides.

Hospitalizations Among Veterans Treated for Metastatic Prostate Cancer With Abiraterone or Enzalutamide.

BACKGROUND: Abiraterone and enzalutamide are second generation androgen receptor pathway inhibitors (ARPIs) used to treat advanced or metastatic prostate cancer. Without head-to-head comparative studies identifying 1 agent as preferred initial therapy, physician preferences guide initial ARPI choice. This study compares hospitalizations among patients treated initially with abiraterone versus enzalutamide. PATIENTS AND METHODS: United States veterans treated with abiraterone or enzalutamide between May 13, 2011 and December 31, 2019; then compared hospitalization rate during first treatment with ARPI in the Veterans Healthcare Administration. Baseline incidence rate of hospitalization was determined from data 1 year prior to ARPI. Incidence Rate Difference (IRD) was calculated using χ2 test and difference in IRD using Poisson Regression. RESULTS: 19,775 veterans were identified; 13,527 (68.4%) were initially treated with abiraterone and 6248 (31.6%) initially with enzalutamide. The enzalutamide cohort was older (75.8 vs. 74.5 years, P < .001) and had higher baseline comorbidities at ARPI initiation (4.4 vs. 4.0, P < .001). Patients were treated with enzalutamide longer than abiraterone (median 9.0 vs. 8.0 months, P < .001). Total hospitalizations increased from 465 per 1000 person-years in the year prior to treatment with abiraterone to 567 during treatment. Total hospitalizations increased from 417 per 1000 person-years in the year prior to treatment with enzalutamide to 430 during treatment. Total rate of hospitalization increased 22% for abiraterone compared to a 3% increase for enzalutamide in the 12 months after ARPI initiation (P < .0001). Abiraterone was associated with greater increase in rates of acute heart failure, atrial fibrillation, acute kidney injury, urinary tract infections, sepsis, and pneumonia. CONCLUSION: By comparing the rate of hospitalization before vs. during treatment, real world analyses identified a 22% versus 3% increase in hospitalizations with abiraterone compared to enzalutamide respectively, despite being used in a younger population with less comorbid disease. Abiraterone was also associated with higher risk of infections, a novel finding.

The Association of Agent Orange (AO) Exposure with Monoclonal Gammopathy of Undetermined Significance (MGUS) to Multiple Myeloma (MM) Progression: A Population-based Study of Vietnam War Era Veterans.

Background: Herbicide and pesticide exposure (e.g., agent orange [AO]) is associated with an increased risk of multiple myeloma (MM) due to the contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Monoclonal gammopathy of undetermined significance (MGUS) is the precursor state to MM; however, not all patients with MGUS progress to MM. It is unclear whether AO exposure increases the risk of progression of MGUS to MM. Purpose: We aimed to determine the association between AO exposure and progression to MM in a nation-wide study of U.S. Veterans with MGUS. Patients and Methods: This is a population-based cohort study of Vietnam Era Veterans diagnosed with MGUS. A natural language processing (NLP) algorithm was used to confirm MGUS and progression to MM. The association between AO and progression was analyzed using multivariable Fine-Gray subdistribution hazard model with death as a competing event. Veterans who served during the Vietnam War Era from 1/9/1962-5/7/1975 and were diagnosed with MGUS between 10/1/1999-12/31/2021 were included. We excluded patients with missing BMI values, progression within 1 year after MGUS diagnosis date, non-IgG or IgA MGUS, or birth years outside of the range of the AO exposed group, and race other than Black and White. AO exposure and service during 1/9/1962-;5/7/1975 and stratified according to TCDD exposure levels by three time periods: 1/9/1962-11/30/1965 (high), 12/1/1965-12/31/1970 (medium), or 1/1/1971-5/7/1975 (low). The association between AO and progression was analyzed using multivariable Fine-Gray subdistribution hazard model with death as a competing event. Results: We identified 10,847 Veterans with MGUS, of whom 7,996 had AO exposure. Overall, 7.4% of MGUS patients progressed to MM over a median follow-up of 5.2 years. In multivariable analysis, AO exposure from 1/9/1962-11/30/1965, high TCDD exposure, was associated with an increased risk of progression (adjusted hazard ratio 1.48; 95% confidence interval 1.02-2.16), compared to Veterans with no exposure. Conclusions: In patients with MGUS, the high Agent Orange exposure time period is associated with a 48% increased risk of progression to multiple myeloma. This suggests that patients with MGUS and prior Agent Orange exposure or occupational exposure to TCDD (eg. Agricultural workers) may require thorough screening for plasma cell dyscrasias.

Non-bacterial thrombotic endocarditis in a patient with COVID.

Non-bacterial thrombotic endocarditis is mainly associated with malignancies and rheumatological diseases. We report the case of mildly symptomatic COVID-19 infection with non-bacterial aortic valve vegetation complicated by transient ischemic attack (TIA) and pulmonary embolism during his hospitalisation. This case emphasised rare life-threatening complications from a hypercoagulable state related to COVID-19 infection. To the best of our knowledge, this is the third case report of non-bacterial endocarditis in a patient with COVID-19 patients as a potential rare complication of COVID-19.

Venous Thromboembolism Risk in Patients With Newly Diagnosed Multiple Myeloma Treated with Carfilzomib or Bortezomib in Combination With Lenalidomide and Dexamethasone.

BACKGROUND: Multiple myeloma (MM), as well as some treatments for MM, increase the risk of venous thromboembolism (VTE). Prior literature suggests carfilzomib, lenalidomide, and dexamethasone (KRd) may have a higher incidence of thromboembolic events compared with bortezomib, lenalidomide, and dexamethasone (VRd). We aimed to evaluate VTE risk with KRd induction compared to VRd at a large academic medical center in the United States. MATERIALS AND METHODS: We retrospectively reviewed patients with newly diagnosed MM presenting at a single institution. Patients were followed for objectively diagnosed VTE events for 6 months following the start of induction therapy. RESULTS: A total of 209 patients were included, with 69 (33%) receiving KRd and 140 (67%) receiving VRd. Overall, 18 patients (9%) had a VTE event, with 5 (7%) in the KRd cohort and 13 (9%) in the VRd cohort (P = .80). Treatment with KRd was not associated with an increased risk of VTE compared to VRd (HR 0.74; 95% CI 0.26-2.08; P = .57). CONCLUSION: In this cohort, KRd was not associated with an increase in VTE risk compared to VRd, contrary to prior literature.

Mortality in the US Populations With Monoclonal Gammopathy of Undetermined Significance.

This cohort study analyzes a nationally representative sample with a screening test for monoclonal gammopathy of undetermined significance (MGUS) to evaluate overall survival of populations with MGUS compared with those without MGUS among the general population in the US.

Frailty and survival among veterans treated with abiraterone or enzalutamide for metastatic castration-resistant prostate cancer.

INTRODUCTION: Abiraterone and enzalutamide are treatments for metastatic castration-resistant prostate cancer (mCRPC). Due to a lack of head-to-head trials, they are prescribed interchangeably. However, the drugs have different pharmacokinetics and thus may have differing efficacy and adverse effects influenced by patient functional status and comorbid diseases. Additionally, mCRPC mainly affects older adults and since the prevalence of frailty increases with age, frailty is an important patient factor to consider in personalizing drug selection. MATERIALS AND METHODS: We conducted a retrospective observational study of US veterans treated with abiraterone or enzalutamide for mCRPC from September 2014 to June 2017. Frailty was assessed using the Veterans Affairs Frailty Index (VA-FI), which utilizes administrative codes to assign a standardized frailty score. Patients were categorized as frail if VA-FI scores were > 0.2. The primary outcome was difference in overall survival (OS) between the two treatment groups. Cox regression modeling and propensity score matching was used to compare between abiraterone and enzalutamide treatments. RESULTS: We identified 5,822 veterans, 57% of whom were initially treated with abiraterone and 43% with enzalutamide. Frail patients (n = 2,314; 39.7%) were older, with a mean age of 76.1 versus 74.9 years in the non-frail group (n = 3,508; 60.3%, p < 0.001) and had shorter OS compared to non-frail patients regardless of treatment group (18.5 vs. 26.6 months, p < 0.001). Among non-frail patients there was no significant difference in OS between abiraterone and enzalutamide treatment (27.7 vs 26.1 months, p = 0.07). However, frail patients treated with enzalutamide versus abiraterone had improved OS (20.7 vs 17.2 months, p < 0.001). In a propensity score matched analysis of frail patients (n = 2,070), enzalutamide was associated with greater median OS (24.1 vs 20.9 months, p < 0.001). In patients with dementia, enzalutamide was associated with longer OS (19.4 vs. 16.6 months, p = 0.003). DISCUSSION: In this study of 5822 US veterans with mCRPC, treatment with enzalutamide was associated with improved OS compared to abiraterone among frail veterans and veterans with dementia, but not among non-frail veterans. Future studies should evaluate interactions between frailty and cancer treatments to optimize selection of therapy among frail adults.

Survival of veterans treated with enzalutamide and abiraterone for metastatic castrate resistant prostate cancer based on comorbid diseases.

BACKGROUND: Comorbid diseases influence patient outcomes, yet little is known about how comorbidities interact with treatments for metastatic castrate-resistant prostate cancer (mCRPC). No head-to-head trials have compared the efficacy of abiraterone and enzalutamide - oral androgen-receptor targeted agents (ARTAs) for mCRPC. In patients with comorbid disease, outcomes with ARTAs may differ due to disparate mechanisms of action, adverse events, and drug interactions. METHODS: Retrospective observational study of US veterans initiating treatment for mCRPC with abiraterone or enzalutamide between September 2014 and June 2017. Treatment duration and overall survival (OS) was compared based on age and comorbid diseases. The association between ARTA and OS was assessed using Cox proportional hazards and propensity-score matched modeling while adjusting for potential confounders. Sensitivity analyses were performed based on patient age, comorbidities, and subsequent treatments for mCRPC. RESULTS: Of 5822 veterans treated for mCRPC, 43.0% initially received enzalutamide and 57.0% abiraterone. Veterans initially treated with enzalutamide versus abiraterone were older (mean 75.8 vs. 75.0 years) with higher mean Charlson comorbidity index (4.4 vs. 4.1), and higher rates of cardiovascular disease or diabetes (74.2% vs. 70.6%). In the entire population, veterans initially treated with enzalutamide had longer median OS compared to those initially treated with abiraterone (24.2 vs. 22.1 months, p = 0.001). In veterans with cardiovascular disease or diabetes, median treatment duration with enzalutamide was longer (11.4 vs. 8.6 months, p < 0.001) with longer median OS compared to abiraterone (23.2 vs. 20.5 months, p < 0.001). In a propensity score matched cohort, enzalutamide was associated with decreased mortality compared to abiraterone (HR 0.90, 95% CI 0.84-0.96). CONCLUSIONS: Veterans with cardiovascular disease or diabetes had longer treatment duration and OS with enzalutamide compared to abiraterone. Further study of ARTA selection may benefit men with metastatic castrate resistant prostate cancer and likely hormone sensitive prostate cancer, especially among patients with comorbid diseases.

D-dimer predicts venous thromboembolism in multiple myeloma: a nested case-control study.

Background: Clinical risk assessment scores, such as IMPEDE VTE, can identify patients with multiple myeloma (MM) at high-risk of venous thromboembolism (VTE). Refinement of these scores, by including 1 or more biomarkers, could improve risk assessment. Objectives: We sought to determine the association between soluble P-selectin (sP-selectin) and D-dimer with VTE in MM. Methods: We identified 545 patients with newly diagnosed MM. Using a nested case-control design, we identified 38 cases of VTE within 6-months of MM treatment and 137 randomly selected controls. Using logistic regression, we examined the association between D-dimer and sP-selectin with VTE. We also analyzed the association after adjusting for IMPEDE VTE. Results: Each 1-point increase in IMPEDE VTE score was associated with a 27% increase in odds of VTE (odds ratio 1.27; 95% CI 1.08-1.51; c-statistic 0.61; 95% CI 0.51-0.71). There was no association between sP-selectin and VTE. Each one increase in natural log of D-dimer was associated with a 44% increase in odds of VTE, so we assigned points (ranging from -2 to +2) to D-dimer values and incorporated them into IMPEDE VTE, forming IMPEDED VTE. There was a 30% increase in odds of VTE per each 1-point increase in IMPEDED VTE (OR 1.30; 95% CI 1.12-1.52; c-statistic 0.65; 95% CI 0.55-0.75). Conclusion: Among patients with newly diagnosed MM starting chemotherapy, D-dimer was associated with increased odds of developing VTE within the subsequent 6-months. The addition of D-dimer to IMPEDE VTE-IMPEDED VTE-could improve prediction of VTE among patients with MM.

A real-world study of pneumonitis in non-small cell lung cancer patients receiving durvalumab following concurrent chemoradiation.

Background: Locally advanced non-small cell lung cancer (LA-NSCLC) treated with the programmed death-ligand 1 inhibitor durvalumab has been associated with significant rates of pneumonitis, which has led to higher rates of discontinuation of therapy in real-world populations. Thus far there has been no consensus in the literature on the impact of pneumonitis on survival. Methods: This is a retrospective cohort study of veterans receiving durvalumab between 12/5/2017 and 4/15/2020. Participants were identified using VINCI data services. Patients were followed through 9/14/2021. Development of clinical pneumonitis was assessed through review of documentation and graded using CTCAE 4.0 criteria. Univariate logistic regression analysis evaluated for associations between body mass index (BMI), age, race, co-morbidity index, chemotherapy regimen, chronic obstructive pulmonary disease (COPD) severity, and development of clinical pneumonitis. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier methods. Cox proportional hazards models were utilized to evaluate the association between risk of death at 1 and 2 years and candidate predictor variables. Results: A total of 284 patients were included in this study. Sixty-one patients developed clinically significant pneumonitis, 7 patients developed grade 5 pneumonitis (death from pneumonitis). The median OS in patients that developed pneumonitis was 27.8 vs. 36.9 months in patients that did not develop pneumonitis (P=0.22). BMI was found to be a clinical predictor of pneumonitis (P=0.04). COPD severity, race, age at durvalumab start date, chemotherapy regimen, and Romano comorbidity index were not significant predictors of pneumonitis. Cox proportional hazards analysis failed to demonstrate an association between the development of pneumonitis and risk of death in this population. Conclusions: The incidence of clinically significant pneumonitis is higher than noted in the PACIFIC trial in this cohort, however this high rate of pneumonitis does not have an impact on OS or PFS. Obesity was found to be a significant predictor of pneumonitis in this patient population.

Mitigating the risk of venous thromboembolism in patients with multiple myeloma receiving immunomodulatory-based therapy.

Patients with multiple myeloma (MM) have up to a 20-fold increased risk of venous thromboembolism (VTE) compared with the general population, with most events occurring within the first 6 months of diagnosis. Treatment with immunomodulatory drugs (IMiDs) is a strong risk factor for VTE in MM. In a meta-analysis of 2 large, randomized trials comparing anticoagulant thromboprophylaxis vs placebo in ambulatory patients with cancer at high risk of VTE based on a validated risk score, the risk of VTE decreased without increasing the risk of major bleeding. However, few patients with MM participated in these trials (1.1%). Initial guidance for risk-stratifying patients with MM resulted in persistent rates of VTE >10% and highlighted the need for improved VTE risk stratification in patients with MM. Three validated risk scores are now available to quantify risk of VTE in patients with MM: SAVED, IMPEDE VTE, and PRISM scores. Using best available data, thromboprophylaxis should be strongly considered in patients with MM assessed as high risk for VTE, especially newly diagnosed patients receiving IMiD-based combination therapies. However, prospective studies are needed to further validate available models and identify the optimal thromboprophylactic agent for each VTE risk category.

Peri-procedure management of antithrombotic agents and thrombocytopenia for common procedures in oncology: Guidance from the SSC of the ISTH.

Patients with cancer have an increased risk of thrombosis requiring anticoagulants and/or antiplatelet agents, and they can also encounter thrombocytopenia due to cancer itself or cancer therapies. They often undergo many procedures such as tissue or bone marrow biopsies, placement of central access lines, diagnostic or therapeutic draining procedures, lumbar puncture, and more. Management of antithrombotic agents or thrombocytopenia around the time of these procedures is highly variable. In this document, the Hemostasis and Malignancy Subcommittee of the International Society on Thrombosis and Haemostasis aims to provide useful practice guidance in the management of antithrombotic agents and thrombocytopenia around the time of common procedures in patients with cancer.

Venous thromboembolism and risk stratification in hematological malignancies.

Patients with hematologic malignancy have an increased risk of venous thromboembolism (VTE) compared to the general population. This risk is highest during the first months after diagnosis and subsequently decreases over time. The risk of VTE in leukemia ranges from less than 1% to almost 7% within the first 6-months of diagnosis, and is higher in patients with acute leukemia compared to chronic leukemia. The risk of VTE in lymphoma ranges from less than 1% to almost 20% in the first year of diagnosis, varying by lymphoma type. Risk is lowest in patients with indolent lymphoma and highest in those with aggressive lymphoma, including central nervous system (CNS) lymphoma. The risk of VTE in multiple myeloma is highest in the first 6-months of diagnosis and decreases over time. Despite incorporation of thromboprophylaxis strategies in many patients, 6-month incidence of VTE remains greater than 10%. Primary thromboprophylaxis has the potential to decrease risk of VTE in patients at high-risk. Clinical risk prediction models can quantify risk of VTE, thereby identifying those at high-risk. VTE risk prediction models are available for patients with leukemia, lymphoma and multiple myeloma. However, these models either require external validation or have room for improvement in VTE risk discrimination. Future efforts should focus in validation of available models, incorporation of biomarkers as predictors of VTE, and evaluation of the risk/benefit of thromboprophylaxis in high risk patients.

Thrombosis and bleeding in hematological malignancy.

Venous (VTE) and arterial (ATE) thromboemboli are a leading cause of morbidity and mortality in patients with cancer. Patients with hematological malignancies are at an exceptionally high risk of both VTE and ATE. This risk varies based on patient- and disease-specific risk factors and can be predicted using risk prediction models for some types of hematological malignancies. Treatment of VTE for patients with hematological malignancies is largely based on randomized control trials that predominately enrolled patients with solid tumors. However, treatment must be balanced with the risk of anticoagulant or antiplatelet therapy in this unique patient population that can have a competing risk of bleeding. In this review, we present the evidence that addresses the risk and prediction of VTE, ATE and bleeding in patients with hematological malignancies and considerations for treatment of these conditions.

Standardization of risk prediction model reporting in cancer-associated thrombosis: Communication from the ISTH SSC subcommittee on hemostasis and malignancy.

Since the development of the Khorana score to predict risk of cancer-associated venous thromboembolism (VTE), many modified and de novo risk prediction models (RPMs) have been proposed. Comparison of the prognostic performance across models requires comprehensive reporting and standardized methods for model development, validation and evaluation. To improve the standardization of RPM reporting, the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD) tool was published in 2015. To better understand the quality of reporting and development of RPMs for cancer-associated VTE, we performed a literature search of published RPMs and assessed each model using the TRIPOD checklist. Our results yielded 29 RPMs for which 30 items were evaluated. There was a non-significant (p = 0.15) improvement in reporting of the 30 items in the post-TRIPOD era (81%) versus the pre-TRIPOD era (75%). Of seven items (title, sample size, missing data handling, baseline demographics, methods and results for model performance, and supplemental resources) with the lowest reporting in the pre-TRIPOD era (<70%), there was an average improvement of 22% in the post-TRIPOD era. Only two of the 22 studies published in the post-TRIPOD era acknowledged compliance with TRIPOD. Informed by the results of this assessment, the Scientific and Standardization Committee (SSC) Subcommittee on Hemostasis & Malignancy of the International Society on Thrombosis and Hemostasis (ISTH) advocates for standardization of four key elements of RPMs for cancer-associated VTE: (1) inclusion of the TRIPOD checklist, (2) clear definition of the derivation population, with justification of sample size, (3) clear definition of predictors, and (4) external validation prior to implementation.

Unanswered questions in cancer-associated thrombosis.

Cancer-associated venous thromboembolism (VTE) is a leading cause of morbidity and mortality in patients with cancer. Treatment of cancer-associated VTE comes with a heightened risk of anticoagulant-related bleeding that differs by choice of anticoagulant as well as by patient- and disease-specific risk factors. Available data from randomized controlled trials and observational studies in cancer-associated VTE suggest that direct oral anticoagulants are effective, continuing anticoagulation beyond six months is indicated in those with active cancer and that patients who develop 'breakthrough' thrombotic events can be effectively treated. We review the evidence that addresses these key clinical questions and offer pragmatic approaches in individualizing care. While significant investigative efforts over the past decade have made impactful advances, future research is needed to better define the factors that contribute to anticoagulant-related bleeding and VTE recurrence, in order to aid clinical decision-making that improves the care of patients with cancer-associated VTE.

Evaluation of the Khorana score for prediction of venous thromboembolism in patients with multiple myeloma.

BACKGROUND: Guidelines recommend thromboprophylaxis for patients with multiple myeloma (MM) at high risk for venous thromboembolism (VTE). However, the optimal risk prediction model for VTE in MM remains unclear. Khorana et al developed a VTE risk score (Khorana score) in ambulatory cancer patients receiving chemotherapy. We aimed to evaluate the predictive ability of the Khorana score in patients with MM. METHODS: We identified patients with MM within the Veterans Affairs health care system between 2006 and 2013. The Khorana score was calculated before treatment initiation. Using logistic regression, the relationship between risk group and VTE was assessed at 3 and 6 months. We tested model discrimination using the concordance statistic. RESULTS: In the cohort of 2870 patients with MM, there were 1328 at low risk (0 points), 1521 at intermediate risk (1-2 points), and 21 at high risk (≥3 points) for VTE by the Khorana score. The 6-month cumulative incidence of VTE was 5.1% (95% confidence interval [CI], 4.0%-6.4%) in low risk, 3.9% (95% CI, 3.0%-5.0%) in intermediate risk, 4.8% (95% CI, 0.3%-20.2%) in high risk. The Khorana score did not strongly discriminate between patients who did and did not develop VTEs at 3 or 6 months (concordance statistic, 0.58; 95% CI, 0.54-0.63; and 0.53, 95% CI, 0.50-0.57, respectively. CONCLUSIONS: In conclusion, in this cohort of 2870 patients with MM, the Khorana score did not predict VTE. Our study supports the need to use myeloma-specific risk models to predict VTE risk in patients with MM.

Characteristics and outcomes of patients on concurrent direct oral anticoagulants and targeted anticancer therapies-TacDOAC registry: Communication from the ISTH SSC Subcommittee on Hemostasis and Malignancy.

BACKGROUND: Cancer patients are increasingly prescribed direct oral anticoagulants (DOACs) and targeted anticancer therapies, but limited data are available on the outcomes during concurrent use. OBJECTIVES: We conducted an international registry through the Scientific and Standardization Committee of the ISTH to evaluate the characteristics, bleeding, and thrombotic outcomes in patients receiving concurrent DOACs and targeted anticancer therapies. PATIENTS/METHODS: Patients receiving concurrent DOACs for venous thromboembolism (VTE) or atrial fibrillation and selected targeted anticancer therapies were followed for 6 months after the start of concurrent use. Data including patient and cancer characteristics, major bleeding, non-major bleeding events, and venous or arterial thromboses were collected. RESULTS: Two hundred and two patients were included from six institutions in the United States and Israel. The most common malignancies were hematologic (N = 57, 28.2%), followed by breast (N = 50, 24.8%) and lung (N = 44, 21.8%). The most common anticancer therapies were epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors (N = 43, 21.3%), followed by Bruton's tyrosine kinase (BTK) inhibitors (N = 42, 20.8%) and palbociclib (N = 42, 20.8%). During follow-up, there were 9 major bleeding and 12 non-major bleeding events, corresponding to cumulative incidences of 4% (95% confidence interval [CI]: 2-8%) and 6% (95% CI: 3-10%), respectively. The cumulative incidence of major bleeding events was highest in BTK inhibitor users (10%). There were 3 VTE and 2 arterial thromboses, corresponding to cumulative incidences of 1.5% (95% CI: 0.4-4.0%) and 1.0% (95% CI: 0.2-3.3%), respectively. CONCLUSIONS: In this cohort receiving concurrent DOACs and targeted anticancer therapies, the incidence of bleeding is higher compared to thrombosis, particularly with BTK inhibitors. Future larger prospective studies are needed.