Venous thromboembolism (VTE) incidence and risk factors in patients (pts) with non-small cell lung cancer (NSCLC) receiving front-line therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19293-e19293
Author(s):  
Jai Narendra Patel ◽  
Myra M. Robinson ◽  
Hailey Hill ◽  
Lauren Lu ◽  
Daniel Slaughter ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
Checkpoint Inhibitors ◽  
Competing Risk ◽  
Tumor Type ◽  
First Line ◽  
Treatment Groups ◽  
Vein Thrombosis ◽  
Diagnosis Codes ◽  
Treatment Type

e19293 Background: VTE incidence varies based on factors such as tumor type, stage, and treatment. There is limited data on VTE incidence and risk factors in NSCLC pts receiving first-line therapies, including immune checkpoint inhibitors (ICIs) and targeted therapies (TTs). Methods: This is a single institution retrospective cohort study of adult NSCLC pts who received first-line treatment between July 2003 and July 2019. Treatments included chemotherapy (chemo) (platinums, taxanes, pemetrexed, gemcitabine, etoposide, bevacizumab), ICI (pembrolizumab, nivolumab, atezolizumab, durvalumab), chemo + ICI, or TT (erlotinib, gefitinib, afatinib, osimertinib, crizotinib, alectinib, ceritinib). Diagnosis codes (ICD 9/10 codes) confirmed VTE (deep vein thrombosis and/or pulmonary embolism) and presence of risk factors which are summarized in Table. Landmark VTE incidence was estimated from cumulative incidence curves for time to VTE, death as a competing risk. Time to VTE distributions were compared between groups with Gray’s tests. Univariable and multivariable competing risk analyses identified risk factors for time to VTE. Results: In 1,618 evaluable pts, the median age was 66 years, 53% were male, 79% White, 18% Black, 58% had adenocarcinoma, 32% squamous cell carcinoma, and 47% metastatic disease. 1178 received chemo, 172 ICIs, 157 chemo + ICI, and 111 TTs. 6-month VTE rates per arm were 5.3%, 7.0%, 7.2%, and 12.0% and 12-month rates were 8.9%, 8.1%, 11.7%, and 13.3%, respectively. Cumulative incidence of VTE was not significantly different between treatment groups (p = .27). Univariable and multivariable analyses are summarized in the Table below. Conclusions: Treatment type was not associated with VTE risk in first-line NSCLC, but rates were numerically highest in pts receiving TTs. Khorana risk score was significantly associated with VTE risk and may identify those likely to benefit from thromboprophylaxis. [Table: see text]

scholarly journals POS0210 THE INCIDENCE AND RISK FACTORS OF RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 322-322
Author(s):  
B. Samhouri ◽  
R. Vassallo ◽  
S. Achenbach ◽  
V. Kronzer ◽  
J. M. Davis ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Cumulative Incidence ◽  
Population Based ◽  
Competing Risk ◽  
Olmsted County ◽  
Research Support ◽  
Risk Of Death

Background:Rheumatoid arthritis (RA) is a systemic inflammatory disease of the joints and other organs, including the lungs.1 Interstitial lung disease (ILD) is a lung injury pattern associated with significant symptom burden and poor outcomes in RA.2 Better understanding of its risk factors could help with disease prevention and treatment.Objectives:Using a population-based cohort, we sought to ascertain the incidence and risk factors of RA-associated ILD (RA-ILD) in recent years.Methods:The study included adult residents of Olmsted County, Minnesota with incident RA between 1999 and 2014 based on the 1987 ACR classification criteria.3 Study subjects were followed until death, migration, or 4/30/2019. ILD was defined by the presence of bilateral interstitial fibrotic changes (excluding biapical scarring) on chest computed tomography (CT). In the absence of chest CT imaging, a physician’s diagnosis of ILD in conjunction with chest X-ray findings suggestive of ILD and a restrictive pattern on pulmonary function testing (defined as a total lung capacity less than the lower limit of normal) was considered diagnostic of ILD. Evaluated risk factors included age, sex, calendar year, smoking status, body mass index (BMI) and presence/absence of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). Cumulative incidence of ILD was adjusted for the competing risk of death. Cox models were used to assess the association between potential risk factors and the development of RA-ILD.Results:In Olmsted County, 645 residents were diagnosed with RA between 1999 and 2014. Seventy percent of patients were females, and 30% were males; median age at RA diagnosis was 55.3 [IQR 44.1-66.6] years, and most patients (89%) were white. Fifty-three percent of patients were never-smokers, and 64% had seropositive RA. Forty percent were obese (i.e., BMI ≥30 kg/m2); median BMI was 28.3 [IQR 24.3-33.0] kg/m2.In the cohort, ILD was identified in 73 patients. The ILD diagnosis predated RA diagnosis in 22 patients (3.4%) who were excluded from subsequent analyses. Final analyses included the remaining 623 patients with no ILD preceding, or at the time of RA diagnosis. Over a median follow-up interval of 10.2 [IQR 6.5-14.3] years, 51 patients developed ILD. Cumulative incidence of ILD, adjusted for the competing risk of death, was 4.3% at 5 years; 7.8% at 10 years; 9.4% at 15 years; and 12.3% at 20 years after RA diagnosis (Figure 1).Age, and history of smoking at RA diagnosis correlated with the incidence of ILD; adjusted hazard ratios (HRs) were 1.89 per 10-year increase in age (95% confidence interval 1.52-2.34) and 1.94 (95% confidence interval 1.10-3.42), respectively. On the other hand, sex (HR: 1.21; 95% CI: 0.68-2.17), BMI (HR: 0.99; 95% CI: 0.95-1.04), obesity (HR: 0.89; 95% CI: 0.50-1.58), and seropositivity (HR: 1.15; 95% CI: 0.65-2.03) did not demonstrate significant associations with ILD.Conclusion:This study provides a contemporary estimate of the occurrence of ILD in a well-characterized population-based cohort of patients with RA. Our findings of a lack of association between sex, obesity and seropositivity with ILD may indicate a change in established risk factors for ILD and warrant further investigation.References:[1]Shaw M, Collins BF, Ho LA, Raghu G. Rheumatoid arthritis-associated lung disease. Eur Respir Rev. 2015;24(135):1-16. doi:10.1183/09059180.00008014[2]Bongartz T, Nannini C, Medina-Velasquez YF, et al. Incidence and mortality of interstitial lung disease in rheumatoid arthritis - A population-based study. Arthritis Rheum. 2010;62(6):1583-1591. doi:10.1002/art.27405[3]Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-2581. doi:10.1002/art.27584Figure 1.Cumulative incidence of ILD in patients diagnosed with RA between 1999 and 2014, adjusted for the competing risk of death. Abbreviations. ILD: interstitial lung disease; RA: rheumatoid arthritis.Disclosure of Interests:Bilal Samhouri: None declared, Robert Vassallo Grant/research support from: Research grants from Pfizer, Sun Pharmaceuticals and Bristol Myers Squibb, Sara Achenbach: None declared, Vanessa Kronzer: None declared, John M Davis III Grant/research support from: Research grant from Pfizer., Elena Myasoedova: None declared, Cynthia S. Crowson: None declared

scholarly journals Dermo-Hipodermites Bacterianas Agudas Não Necrotizantes: Erisipela e Celulite Infeciosa

2021 ◽  
Vol 34 (3) ◽  
pp. 217
Author(s):  
Maria Alexandra Rodrigues ◽  
Mónica Caetano ◽  
Isabel Amorim ◽  
Manuela Selores
Keyword(s):  
Risk Factors ◽  
Necrotizing Fasciitis ◽  
Lower Limbs ◽  
First Line ◽  
Correct Treatment ◽  
Vein Thrombosis ◽  
Group A ◽  
Low Sensitivity ◽  
Atypical Presentations ◽  
Main Complication

Non-necrotizing acute dermo-hypodermal infections are infectious processes that include erysipela and infectious cellulitis, and are mainly caused by group A β-haemolytic streptococcus. The lower limbs are affected in more than 80% of cases and the risk factors are disruption of cutaneous barrier, lymphoedema and obesity. Diagnosis is clinical and in a typical setting we observe an acute inflammatory plaque with fever, lymphangitis, adenopathy and leucocytosis. Bacteriology is usually not helpful because of low sensitivity or delayed positivity. In case of atypical presentations, erysipela must be distinguished from necrotizing fasciitis and acute vein thrombosis. Flucloxacillin and cefradine remain the first line of treatment. Recurrence is the main complication, so correct treatment of the risk factors is crucial.

scholarly journals Upper Extremity Deep Vein Thrombosis in Acute Leukemia and Non-Hodgkin's Lymphoma: Analysis of the California Cancer Registry

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 932-932
Author(s):  
Christina Poh ◽  
Ann M Brunson ◽  
Theresa H.M. Keegan ◽  
Ted Wun ◽  
Anjlee Mahajan
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Deep Vein Thrombosis ◽  
Major Bleeding ◽  
Cumulative Incidence ◽  
Steering Committee ◽  
Vein Thrombosis ◽  
California Cancer Registry ◽  
Increased Risk ◽  
Deep Vein

Background Venous thromboembolism (VTE) is a known complication in patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and non-Hodgkin's lymphoma (NHL). However, the cumulative incidence, risk factors, rate of subsequent VTE and impact on mortality of upper extremity deep vein thrombosis (UE DVT) in these diseases is not well-described. Methods Using the California Cancer Registry, we identified patients with a first primary diagnosis of AML, ALL and NHL from 2005-2014 and linked these patients with the statewide hospitalization and emergency department databases to identify an incident UE DVT event using specific ICD-9-CM codes. Patients with VTE prior to or at the time of malignancy diagnosis or who were not treated with chemotherapy were excluded. We determined the cumulative incidence of first UE DVT, adjusted for the competing risk of death. We also examined the cumulative incidence of subsequent VTE (UE DVT, lower extremity deep vein thrombosis (LE DVT) and pulmonary embolism (PE)) and major bleeding after incident UE DVT. Using Cox proportional hazards regression models, stratified by tumor type and adjusted for other prognostic covariates including sex, race/ethnicity, age at diagnosis, neighborhood, sociodemographic status and central venous catheter (CVC) placement, we identified risk factors for development of incident UE DVT, the effect of incident UE DVT on PE and/or LE DVT development, and impact of incident UE DVT on cancer specific survival. The association of CVC placement with incident UE DVT was not assessed in acute leukemia patients, as all who undergo treatment were assumed to have a CVC. Results are presented as adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results Among 37,282 patients included in this analysis, 6,213 had AML, 3,730 had ALL and 27,339 had NHL. The 3- and 12-month cumulative incidence of UE DVT was 2.6% and 3.6% for AML, 2.1% and 3% for ALL and 1.0% and 1.6% for NHL respectively (Figure 1A). Most (56-64%) incident UE DVT events occurred within the first 3 months of malignancy diagnosis. African Americans (HR 1.66; CI 1.22-2.28) and Hispanics (HR 1.35; CI 1.10-1.66) with NHL had an increased risk of incident UE DVT compared to non-Hispanics Whites. NHL patients with a CVC had over a 2-fold increased risk of incident UE DVT (HR 2.05; CI 1.68-2.51) compared to those without a CVC. UE DVT was a risk factor for development of PE or LE DVT in ALL (HR 2.53; CI 1.29-4.95) and NHL (HR 1.63; CI 1.11-2.39) but not in AML. The 12-month cumulative incidence of subsequent VTE after an incident UE DVT diagnosis was 6.4% for AML, 12.0% for ALL and 7.6% for NHL. 46-58% of subsequent VTEs occurred within the first 3 months of incident UE DVT diagnosis. The majority of subsequent VTEs were UE DVT which had a 12-month cumulative incidence of 4.6% for AML, 6.6% for ALL and 4.0% for NHL (Figure 1B). The 12-month cumulative incidence of subsequent LE DVT was 1.3% for AML, 1.6% for ALL and 1.9% for NHL (Figure 1C). The 12-month cumulative incidence of subsequent PE was 0.4% for AML, 4.1% for ALL and 1.8% for NHL (Figure 1D). The 12-month cumulative incidence of major bleeding after an UE DVT diagnosis was 29% for AML, 29% for ALL and 20% for NHL. Common major bleeding events included gastrointestinal (GI) bleeds, epistaxis and intracranial hemorrhage. GI bleeding was the most common major bleeding event among all three malignancies (14.2% in AML, 9.6% in ALL and 12.4% in NHL). The rate of intracranial hemorrhage was 6% in AML, 3.5% in ALL and 1.7% in NHL. A diagnosis of incident UE DVT was associated with an increased risk of cancer-specific mortality in all three malignancies (HR 1.38; CI 1.16-1.65 in AML, HR 2.16; CI 1.66-2.82 in ALL, HR 2.38; CI 2.06-2.75 in NHL). Conclusions UE DVT is an important complication among patients with AML, ALL and NHL, with the majority of UE DVT events occurring within the first 3 months of diagnosis. The most common VTE event after an index UE DVT was another UE DVT, although patients also had subsequent PE and LE DVT. UE DVT was a risk factor for development of PE or LE DVT in ALL and NHL, but not in AML. Major bleeding after an UE DVT was high in all three malignancies (>20%), with GI bleeds being the most common. UE DVT in patients with AML, ALL and NHL is associated with increased risk of mortality. Disclosures Wun: Janssen: Other: Steering committee; Pfizer: Other: Steering committee.

scholarly journals The Incidence of Cancer Associated Thrombosis is Increasing Over Time

2021 ◽  
Author(s):  
Anjlee Mahajan ◽  
Ann Brunson ◽  
Oyebimpe Adesina ◽  
Theresa HM Keegan ◽  
Ted Wun
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
Temporal Trends ◽  
Individual Risk ◽  
Cancer Type ◽  
Tumor Type ◽  
Risk Of Death ◽  
Breast And Prostate Cancer ◽  
Cancer Associated Thrombosis ◽  
Over Time

Cancer associated thrombosis (CAT) is an important cause of morbidity and mortality for patients with malignancy and varies by primary cancer type, stage and therapy. We aimed to characterize the incidence, risk factors, temporal trends and the effect on mortality of CAT. The California Cancer Registry was linked to the statewide hospitalization database to identify individuals with the 13 most common malignancies diagnosed 2005 -2017 and determine the 6 and 12-month cumulative incidence of CAT by venous thromboembolism (VTE) location, tumor type and stage after adjusting for competing risk of death. Cox proportional hazard regression models were used to determine risk factors associated with CAT and the effect of CAT on all-cause mortality. 942,019 patients with cancer were identified; 62,003 (6.6%) had an incident diagnosis of CAT. Patients with pancreatic, brain, ovarian, and lung cancer had the highest and patients with breast and prostate cancer had the lowest 12-month cumulative incidence of CAT. For most malignancies, men, those with metastatic disease and more co-morbidities, and African-Americans (vs. non-Hispanic Whites) were at highest risk for CAT. Patients diagnosed with cancer 2014-2017 had higher risk of CAT compared to those diagnosed 2005-2007. CAT was associated with increased overall mortality for all malignancies (HR ranges 1.89 - 4.79). The incidence of CAT increased over time and was driven by an increase in PE±DVT. CAT incidence varies based on tumor type and stage, and on individual risk factors including gender, race/ethnicity, and co-morbidities. For all tumor types CAT is associated with an increased mortality.

scholarly journals Timing of steroid initiation and response rates to immune checkpoint inhibitors in metastatic cancer

2021 ◽  
Vol 9 (7) ◽  
pp. e002261
Author(s):  
Diana V Maslov ◽  
Karine Tawagi ◽  
Madhav KC ◽  
Victoria Simenson ◽  
Helen Yuan ◽  
...  
Keyword(s):  
Survival Data ◽  
Immune Checkpoint ◽  
Cell Function ◽  
Checkpoint Inhibitors ◽  
Metastatic Cancer ◽  
Objective Response ◽  
P Value ◽  
Cancer Type ◽  
Tumor Type ◽  
Treatment Type

BackgroundCorticosteroids (CS) are the mainstay of immune-related adverse effect (irAE) management, as well as for other indications in cancer treatment. Previous studies evaluating whether CS affect immune checkpoint inhibitor (CPI) efficacy compared patients receiving CS versus no CS. However, there is a paucity of clinical data evaluating the timing of concomitant CS and CPI efficacy.MethodsWe retrospectively collected data from patients who received CS during CPI treatment at a single institution. Patients were in two cohorts based on timing of initiation of CS (≥2 months vs <2 months after initiating CPI). Patient characteristics, irAEs, cancer type, treatment type, treatment response/progression per RECIST V.1.1, and survival data were collected. Kaplan-Meier and Cox proportional hazard regression methods estimated HRs for the primary endpoint of progression-free survival (PFS) along with overall survival (OS).ResultsWe identified 247 patients with metastatic cancer who received CS concurrently with CPIs. The median time on CS was 1.8 months. After adjusting for treatment type, tumor type, brain metastases, and irAEs, those treated with CS ≥2 months after starting CPI had a statistically significant longer PFS (HR=0.30, p<0.001), and OS (HR 0.34, p<0.0001) than those who received CS <2 months after starting CPI. Objective response rate (ORR) for patients on CS ≥2 months was 39.8%, versus ORR for patients <2 months was 14.7% (p value =<0.001)ConclusionOur results suggest that early use of CS during CPI treatment significantly hinders CPI efficacy. This data needs to be validated prospectively. Future studies should focus on the immune mechanisms by which CSs affect T-cell function early in the CPI treatment course.

scholarly journals Incidence and risk factors of pulmonary hypertension after venous thromboembolism: An analysis of a large healthcare database

2020 ◽  
Author(s):  
Pamela L. Lutsey ◽  
Kurt W. Prins ◽  
Line H. Evensen ◽  
Rob F. Walker ◽  
Joel F. Farley ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Hypertension ◽  
Venous Thromboembolism ◽  
Cumulative Incidence ◽  
Administrative Databases ◽  
World Population ◽  
Healthcare Database ◽  
Vein Thrombosis ◽  
Sex Risk ◽  
Hazard Ratios

AbstractBackgroundPulmonary hypertension (PH) is a devastating potential complication of pulmonary embolism (PE), a manifestation of venous thromboembolism (VTE). The incidence of and risk factors for PH in those with prior VTE is poorly characterized.MethodsICD codes from inpatient and outpatient medical claims from MarketScan administrative databases for years 2011-2018 were used were used to identify cases of VTE, comorbidities prior to the VTE event, and PH occurring subsequent to the VTE event. Cumulative incidence and hazard ratios (HR), and their 95% confidence intervals (CI), were calculated.ResultsThe 170,021 VTE cases included in the analysis were on average (± SD) 57.5 ± 15.8 years old and 50.5% were female. A total of 5,946 PH cases accrued over an average follow-up of 1.94 years. Two years after incident VTE the cumulative incidence (95% CI) of PH was 3.5% (3.4%, 3.7%) overall. It was higher among women [3.9% (3.8%-4.1%)] than men [3.2% (3.0%-3.3%)], and among patients presenting with PE [6.2% (6.0%-6.5%)] than those presenting with deep vein thrombosis-only [1.1% (1.0%-1.2%)]. Adjusting for age and sex, risk of PH was higher among VTE patients with underlying comorbidities. The strongest associations were observed with concomitant heart failure [HR: 2.17 (1.04-2.31)], chronic pulmonary disease [2.01 (1.90-2.14)], and myocardial infarction [1.53 (1.40-1.67)].ConclusionsIn this large real-world population of insured people with VTE, 3.5% developed PH in the 2 years following their initial VTE event. Risk was higher among women, with increasing age, and in those with additional comorbidities at the time of the VTE event. These data provide insights into the burden of PH and risk factors for PH among VTE patients.

scholarly journals Risk of Venous Thromboembolism in Patients with Lung Cancer Treated with Immune Checkpoint Inhibitors

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3223-3223
Author(s):  
Doaa Attia ◽  
Wei Wei ◽  
Nathan A Pennell ◽  
Keith R. McCrae ◽  
Alok A Khorana ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Venous Thromboembolism ◽  
Incidence Rate ◽  
Immune Checkpoint ◽  
Cumulative Incidence ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Rank Test ◽  
Cumulative Incidence Rate ◽  
Vein Thrombosis

Abstract Background: Thromboembolism (TE) in cancer significantly contributes to morbidity and mortality. Cancer immunotherapy is linked to several inflammatory immune mediated adverse events. Inflammation plays a key role in thrombosis but the association between immunotherapy and venous thromboembolism (VTE) has not been thoroughly investigated. Here, we report the incidence of thromboembolism in patients with lung cancer treated with immune checkpoint inhibitors (ICIs). Methods: A single institution retrospective cohort of 514 adult patients with lung cancer who received ICIs (pembrolizumab, nivolumab, atezolizumab, ipilumab, avelumab) between 2013 and 2017 was included. Diagnosis of VTE (deep vein thrombosis and/or pulmonary embolism, and visceral vein thrombosis "VVT") was confirmed by imaging. Overall survival (OS) was estimated by Kaplan-Meier and compared using log rank test. Cumulative incidence rate of VTE was estimated and compared using Gray's method. Results: Of 514 patients (pts), 58.75% were males, 83.27% were white with a median age of 67 (range 22-91). Nivolumab was most commonly used (52.14%), followed by Pembrolizumab (30.16%), Atezolizumab (10.89%), combination of ipilimumab plus nivolumab (6.61), ipilimumab (2.33%), Avelumab (1.17%). 88.52% had stage 4 disease at treatment initiation. VTE events occurred in 62 pts (12%) (3.5% DVT, 4.47% PE, 2.72% both, 0.97 VVT, 0.19 VVT + PE, 0.19% VVT+DVT+PE). The cumulative incidence rate of VTE of all pts at 6-month and 1-year post IO was 7.6% (95% CI:5.3-9.9%) and 11.6% (95% CI:8.7-14.6%) respectively. The rate of survival without VTE at 6 months after IO treatment was 91% (95% CI: 89-94%). None of the following factors (age, gender, race, cancer staging, IO type or line) were significantly associated with time-to-VTE (TTVTE) survival post treatment (P &gt;0.05). Median OS of all pts was 12.6 months (95% CI: 11.0-16.7 months), with 2-year OS rate of 35% (95% CI: 31-41%). Conclusion: ICIs in lung cancer are associated with higher VTE risk within six months and a year of initiation of treatment. Further studies are needed to investigate the risk factors for ICIs-associated VTE. Disclosures Pennell: Astrazeneca: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; G1 therapeutics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Mirati Therapeutics, Inc.: Consultancy, Honoraria; Viosera Therapeutics: Consultancy, Honoraria; Eli Lilly: Consultancy, Honoraria; BMS: Consultancy, Honoraria. McCrae: Sanofi, Novartis, Alexion, and Johnson & Johnson: Consultancy, Honoraria; Dova, Novartis, Rigel, and Sanofi Genzyme: Consultancy. Khorana: Pfizer: Consultancy, Honoraria; Anthos: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Halozyme: Consultancy, Honoraria; Bayer: Consultancy, Honoraria.

scholarly journals High Incidence of Bleeding Found with Direct Oral Anticoagulant Use in Myeloproliferative Neoplasm Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3632-3632
Author(s):  
Chi-Joan How ◽  
Charlotte McIlwaine Story ◽  
Siyang Ren ◽  
Donna S. Neuberg ◽  
Rachel P. Rosovsky ◽  
...  
Keyword(s):  
Risk Factors ◽  
Board Of Directors ◽  
Median Duration ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Practice Patterns ◽  
Recurrent Thrombosis ◽  
Advisory Committees ◽  
Bleeding Rate ◽  
Vein Thrombosis

Abstract BACKGROUND: Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are at increased risk of arterial (ATE) and venous thromboembolism (VTE). There are no clear guidelines regarding selection of anticoagulation (AC) in MPN patients. Direct oral anticoagulants (DOACs) are increasingly used in the general population to treat a variety of conditions including VTE, ATE, and atrial fibrillation (AF). Data on the safety and efficacy of DOACs in MPNs limited. We conducted a multi-center, retrospective analysis of DOAC use in MPN patients to characterize real-world practice patterns and evaluate thrombosis and bleeding risks. METHODS: We retrospectively analyzed 133 MPN patients prescribed DOACs across the Massachusetts General Brigham / Dana Farber Harvard Cancer Center system from 1995 to 2020. Patients were identified using ICD-9 and 10 codes in the electronic medical record. Patient and treatment characteristics were described with summary statistics. We calculated cumulative incidence functions of VTE and ATE, and major and clinically relevant non-major bleeding (CRNMB) by ISTH criteria, using death on DOAC as a competing risk. A Gray's test was used to compare cumulative incidence between groups. Analysis of risk factors associated with bleeding/thrombosis was carried out by univariate and multivariable Fine-Gray models. RESULTS: Baseline characteristics are displayed in Table 1. Seventy-five (56.4%) MPN patients were prescribed DOAC for VTE, 46 (34.6%) for AF, 7 (5.3%) for stroke, and 5 for other ATE (3.8%). The median age at DOAC initiation was 71; the AF population was significantly older than patients with VTE (75 vs 59, p&lt;0.001). Fifty-seven percent of patients (N = 76) had a diagnosis of PV, with 89% (N = 118) of patients carrying a JAK2 driver mutation. Apixaban was the most commonly prescribed DOAC (N = 83, 62.4%). Nearly half (N = 59, 45%) of patients had a prior VTE/ATE at DOAC initiation, and 23% (N = 31) of patients were switched from warfarin. Among the VTE-treated patients, 43% of events were deep vein thrombosis (N = 39), 31% (N = 28) were pulmonary embolism, 21% (N = 19) were splanchnic vein thrombosis (SVT), and 4.4% (N=4) were other VTE. Table 2 displays practice patterns of DOAC use in MPN patients. The median duration of AC was 37.0 months for all patients, with no difference (p=0.01) between patients treated for AF (42.3 months) and VTE (37.0 months). Twenty-one percent of VTE-treated patients completed a finite course of AC of 6 months median duration. Fifteen percent (N = 11) of VTE-treated and 4.3% (N = 2) of AF patients had reduction to prophylactic dosing. Fifty percent (N = 66) of patients took aspirin and AC concurrently; 83% (N = 110) of patients took cytoreduction with AC. After a median follow-up of 37 months, we found 12 thrombotic (7 arterial, 3 venous, 2 TIPS occlusions) and 28 bleeding (6 major with 4 contributing to patient death, 2 CRNMB) events on DOAC. The estimated 1-year cumulative incidence of thrombosis and bleeding on DOAC was 5.5% (1.5%-9.5%) and 12.3% (6.4%-18.2%), respectively (Figure 1). Thrombosis and bleeding rates were not significantly different between patients treated for VTE versus AF. Prior history of thrombosis and use of dabigatran or edoxaban were significantly associated with increased thrombosis on both univariate and multivariable analysis (p&lt;0.05). Age ≤ 65 also emerged as a risk factor for recurrent thrombosis in multivariate analysis (p=0.04). Use of dabigatran or edoxaban trended toward increased bleeding, but otherwise we found no significant risk factors for bleeding at α=0.05 level, including concomitant aspirin use. DISCUSSION: DOACs are increasingly prescribed in MPN patients for a wide range of indications, with heterogeneity in practice patterns. In our cohort, 1-year thrombosis and bleeding incidence rates on DOAC were 5.5% and 12.3%, respectively. While our 5.5% thrombosis rate is similar to recurrent thrombosis rates reported in MPN patients on DOACs and VKA, our 12.3% bleeding rate appears much higher. This may be related to the complexity of patients seen at our tertiary referral center. The higher-than-expected bleeding rate found in our study indicates the continued need for rigorous evaluation of DOACs in this population, with the gold standard being randomized controlled trials comparing DOAC with warfarin. Figure 1 Figure 1. Disclosures Neuberg: Madrigal Pharmaceuticals: Other: Stock ownership; Pharmacyclics: Research Funding. Rosovsky: Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Inari: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hobbs: Bayer: Research Funding; Merck: Research Funding; AbbVie.: Consultancy; Celgene/Bristol Myers Squibb: Consultancy; Novartis: Consultancy; Incyte Corporation: Research Funding; Constellation Pharmaceuticals: Consultancy, Research Funding. Connors: Abbott: Consultancy; Bristol-Myers Squibb: Honoraria; takeda: Honoraria; Alnylam: Consultancy; Pfizer: Honoraria; CSL Behring: Research Funding.

Long Term Outcome and Late Effects in Patients Transplanted with Filgrastim-Mobilized Blood or Bone Marrow Treated in a Randomized Trial. A Study from the EBMT Late Effects Working Party

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 451-451 ◽  
Author(s):  
Birte Friedrichs ◽  
Andre Tichelli ◽  
Andrea Bacigalupo ◽  
Nigel H. Russell ◽  
Tapani Ruutu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Late Effects ◽  
Cumulative Incidence ◽  
Competing Risk ◽  
Secondary Malignancy ◽  
Cervix Carcinoma ◽  
Long Term Outcome ◽  
Treatment Groups

Abstract In 2002, the EBMT reported on the largest prospective randomized study comparing filgrastim-mobilized peripheral blood progenitor cell (PBPC) to bone marrow (BM) transplantation (Schmitz et al. Blood 2002). Patient accrual took place between 02/95 and 09/99 and included 329 patients transplanted from HLA-identical sibling donors mostly for early leukaemia (ALL, AML, MDS, CML). Here we report long-term follow-up data collected at a median of 9.1 years (BM 9.2 yrs; PBPC 8.9 yrs) after transplantation. Questionnaires on long-term events of allogeneic transplantation were sent out to the treating centers of all 202 patients surviving at 3 years post-transplant. Follow-up data were available for 162 patients (80.2%; BM n = 86; PBPC n = 76) from 38 of 42 centers (90.4%). The 8-year overall survival (OS) was 46.0 % for PBPC recipients versus 54.1 % for BM recipients (p = 0.23). Leukemia-free survival (LFS) was 43.7% for PBPC recipients versus 46.2% for BM recipients (p = 0.66). Late deaths (&gt; 3 years) occurred in 22 cases (9 BM, 13 PBPC); 8 patients died due to relapse (4 BM, 4 PBPC). While relapse remains the most frequent cause of late deaths, non-relapse mortality included secondary malignancy (n = 1), GvHD (n = 4), brain hemorrhage (n = 2), other/unknown (n = 7), and did not show differences between BM and PBPC. Late relapses (&gt;3 years) occurred in 11 patients (9 BM; 2 PBPC); the cumulative incidence of late relapse with death as competing risk was 18.4% for BM and 6.8% for PBPC (p = 0.056). While for AML and ALL no differences in relapse rate (RR) were found between the two treatment groups, CML patients showed a significantly lower RR after transplantation with PBPC (BM 19.4% PBPC 6.8%; p = 0.036). Fourteen cases of secondary malignancies occurred (5 BM; 9 PBPC) (1 lymphoma, 1 lung cancer, 1 prostate cancer, 2 thyroid cancer, 1 squamous cell cancer, 3 basalioma, 1 histiocytofibroma, 1 ependymoma, 1 tongue carcinoma, 1 breast cancer, 1 cervix carcinoma). For 3-year-survivors, the cumulative incidence of secondary malignancy with death as competing risk was 7.2% for BM and 16.1% in the PBPC group (p = 0.16). Significantly more patients transplanted with PBPC than with BM have developed chronic GvHD (72.6% vs 54.1%, p=0.013) with also a higher cumulative incidence of extensive disease (56.3% vs. 30.4%; p=0.002). Five years after transplantation, 29.4% (20/68) of patients transplanted with PBPC were reported to be still on immunosuppressive drugs, compared to 10.6% (10/75) of the BM group (p=0.004). Nonetheless, there was no difference in mean performance status (mean ECOG = 0.5; range 0–3). Sixty-nine percent of the 3-year survivors have returned to work with no difference between treatment groups. Among 3-year survivors, overall incidence of bronchiolitis obliterans and cataract was 9.8% each, with no differences between the recipients of BM (10.8% and 9.8%) and PBPC (8.7% and 10%). Long-term hematopoietic function was similar in both treatment groups with median concentrations of hemoglobin of 141g/L (range 10.1–17.4) vs. 139g/L (range 10.0–16.6) and median platelet counts of 225G/L (range 120–554) vs. 251G/L (range 109–425) for BM and PBPC recipients, respectively. In conclusion, OS and LFS remain similar between BM and PBPC transplanted recipients with an increasing trend to better OS for patients transplanted with BM. The higher incidence of cGvHD in the PBPC group resulted in longer times of immunosuppression in a higher number of patients. Lower relapse rates in CML for patients transplanted with PBPC might be the consequence of a more intense GvL effect. However, overall these differences did not affect survival outcomes, general health status and the occurrence of late events in recipients treated with BM and PBPC.

scholarly journals 649 Incidence of thromboembolism (TE) in patients with melanoma receiving immune checkpoint inhibitor (ICI) therapy and its adverse impact on survival

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A687-A687
Author(s):  
Tamara Sussman ◽  
Joanna Roopkumar ◽  
Hong Li ◽  
Keith McCrae ◽  
Pauline Funchain ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
Univariate Analysis ◽  
Single Agent ◽  
Cleveland Clinic ◽  
Stage Iv ◽  
Incidence Rates ◽  
Rank Test ◽  
Vein Thrombosis ◽  
Stage Iv Disease

BackgroundLittle is known about rates of arterial thromboembolism (ATE) and venous thromboembolism (VTE) in patients with melanoma on ICI. We assessed incidence and outcomes of ATE and VTE in patients with melanoma receiving ICI.MethodsWe conducted a retrospective cohort study of patients with melanoma receiving ICI from July 2015 through December 2017 at Cleveland Clinic. TE including VTE events of deep venous thrombosis (DVT), pulmonary embolism (PE), visceral vein thrombosis (VVT), and ATE events of myocardial infarction (MI), stroke, or transient ischemic attack (TIA) after ICI initiation were identified. Overall survival (OS) from ICI initiation was estimated by Kaplan-Meier and Cox hazard models; associations between TE, ICI regimen, and clinical risk factors were evaluated using log-rank test.ResultsThe study population comprised 228 patients with median age 65 (23–91) years, 67% male, and median follow up 27.3 months. Pembrolizumab was most commonly used (38.7%), followed by combination ipilimumab plus nivolumab (29.4%), ipilimumab (20%), and nivolumab (12.3%). Most had stage IV disease (81.1%) and 11% had brain metastases (BM) at treatment initiation. Fifty-one TE events occurred in 47 patients (20.6%), including 37 (16.2%) VTE and 14 (6.1%) ATE. Of VTE, DVT comprised 46.0%, PE 24.3%, DVT+PE 21.6%, VVT 5.4%, and DVT+VVT 2.7%. Of ATE, stroke comprised 57.2%, MI 35.7%, and TIA 7.1%. Of all TE events, 72% resulted in hospitalization and 19% resulted in clot-related mortality. Cumulative incidence of TE after ICI initiation was 9.3% (95%CI,6.0–13.6%) at 6 months, and 16.0% (95%CI,11.6–21.2%) at 12 months. The 6- and 12-month VTE cumulative incidence rates were 8.0% (95%CI,4.9–12.0%), and 12.9% (95%CI,8.9–17.7%), respectively. The 6- and 12-month ATE cumulative incidence rates were 2.2% (95%CI,0.84–4.8%), and 4.5% (95%CI,2.3–7.8%), respectively. The 6- and 12-month VTE cumulative incidence rates were higher with combination ICI than single agent (16.7% vs. 5.0% and 21.3% vs. 9.5%, respectively; p=0.02) (figure 1). Risk factors associated with VTE in univariate analysis included BM, stage IV disease, combination ICI, and Khorana score ≥1 (p<0.05 for all). In multivariate analysis, combination ICI (HR 2.21; [95%CI,1.04–4.72]; p=0.04) and Khorana score ≥1 (HR 2.48; [95%CI,1.18–5.20]; p=0.02) remained significantly associated with VTE.Of patients without BM, OS was worse in patients with TE compared to those without (3-year OS 34.9% vs. 62.9%; HR 1.84; [95%CI,1.16–2.93]; p<0.001), when adjusted for age, stage, and Khorana score (figure 2).Abstract 649 Figure 1Cumulative incidence of VTE, stratified by ICI*Death before VTE was considered a competing risk in CIF estimationAbstract 649 Figure 2OS in patients without BM stratified by TE statusConclusionsICI is associated with a high incidence of TE in patients with melanoma; TE is associated with substantial worsening of survival.

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