scholarly journals Safety and Effectiveness of Apixaban, LMWH, and Warfarin Among Venous Thromboembolism Patients with Active Cancer: A Retrospective Analysis Using Four US Claims Databases

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 326-326 ◽  
Author(s):  
Alexander T Cohen ◽  
Allison Keshishian ◽  
Theodore Lee ◽  
Gail Wygant ◽  
Lisa Rosenblatt ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Lower Risk ◽  
Select Committee ◽  
Advisory Committees ◽  
Recurrent Vte ◽  
High Risk Cancer ◽  
Similar Risk ◽  
Active Cancer

BACKGROUND: Venous thromboembolism (VTE) is the second leading cause of death in cancer patients. The treatment of cancer-associated VTE carries a significantly greater risk of major bleeding (MB) and recurrent VTE compared to that in non-cancer patients. CHEST Guidelines suggest the use of low molecular weight heparin (LMWH) over a vitamin K antagonist (VKA) in patients diagnosed with VTE and cancer. The last decade has seen an emergence of non-VKA anticoagulants (NOACs) for the treatment of VTE. Despite completed and ongoing clinical trials, there is a lack of real-world evidence comparing the effectiveness and safety of LWMH with VKAs and NOACs among VTE patients with active cancer. Therefore, this study evaluates the risk of MB, clinically relevant non-MB (CRNMB), and recurrent VTE (fatal or non-fatal) among VTE patients with active cancer prescribed apixaban, LMWH, or warfarin in routine clinical practice. METHODS: Four US commercial insurance claims databases were used to identify VTE patients with active cancer (defined as cancer diagnosis or cancer treatment [chemotherapy, radiation and cancer-related surgery] within 6 months before or 30 days after VTE diagnosis) who initiated apixaban, LMWH, or warfarin within 30-days following the first VTE event (01SEP2014-31MAR2018). Patients who used LMWH as bridging therapy for warfarin (≤14 days before or after warfarin initiation) were classified as warfarin users. Patients were followed to the earliest of: health plan disenrollment, death, index therapy discontinuation, switch to another anticoagulant, study end, or a maximum of 6 months. Additional analysis using all available follow-up was also conducted. Stabilized inverse probability treatment weighting (IPTW) was used to balance treatment cohorts. Cox proportional hazard models were used to evaluate the risk of MB, CRNMB, and recurrent VTE. RESULTS: After applying all eligibility criteria, 3,393 apixaban, 6,108 LMWH, and 4,585 warfarin patients were identified with mean ages of 65, 64, and 64 years, respectively. After IPTW, all patient characteristics were balanced. The mean follow-up was 105, 88, and 113 days for apixaban, LMWH, and warfarin, respectively. Among the weighted VTE cancer population, 51% of the patients had metastatic cancer and 77% of patients received cancer treatment. Further, 15% of patients had very high-risk cancer (brain, stomach, or pancreas), and 40% patients had high-risk cancer (lung, lymphoma, gynecologic, bladder, testicular, renal cell carcinoma). Apixaban patients had a lower risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH. Apixaban patients also had a lower risk of recurrent VTE and a similar risk of MB and CRNM bleeding compared to warfarin. Warfarin patients had a similar risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH (Figure). When the entire available follow-up period (mean follow-up was 137, 106, and 166 days for apixaban, LMWH, and warfarin, respectively) was used, the trends were similar to the 6-month analysis for apixaban vs. LMWH and warfarin vs. LMWH. However, apixaban patients were associated with a lower risk of both MB and recurrent VTE compared to warfarin patients. CONCLUSION: VTE patients with active cancer initiating apixaban had significantly lower risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH patients. Apixaban patients also had a lower risk of recurrent VTE compared to warfarin patients. These results may be helpful for clinicians in evaluating different anticoagulation treatments for VTE patients with active cancer. Further studies are needed to evaluate these outcomes between different anticoagulation treatment options. Figure Disclosures Cohen: Lifeblood: Other: advisor to Lifeblood: the thrombosis charity and is the founder of the European educational charity the Coalition to Prevent Venous Thromboembolism; ONO: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; TRN: Consultancy; UK Government Health Select Committee: Other: advised the UK Government Health Select Committee, the all-party working group on thrombosis, the Department of Health, and the NHS, on the prevention of VTE; Temasek Capital: Consultancy; ACI Clinical: Consultancy; Navigant: Consultancy; McKinsey: Consultancy; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy; Aspen: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Boston Scientific: Consultancy; Boehringer-Ingelheim: Consultancy, Speakers Bureau; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Consultancy; GlaxoSmithKline: Consultancy, Speakers Bureau; GLG: Consultancy; Guidepoint Global: Consultancy; Johnson and Johnson: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Leo Pharma: Consultancy; Medscape: Consultancy, Speakers Bureau. Keshishian:STATinMED Research: Other: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company and Pfizer Inc.. Lee:Pfizer Inc.: Employment, Equity Ownership. Wygant:Bristol-Myers Squibb Company: Employment. Rosenblatt:Bristol-Myers Squibb: Other: Stock Owner ; Bristol-Myers Squibb Company: Employment. Hlavacek:Pfizer Inc.: Employment. Mardekian:Pfizer Inc.: Employment. Wiederkehr:Pfizer Inc.: Employment. Sah:STATinMED Research: Other: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company and Pfizer Inc.. Luo:Pfizer Inc.: Employment.

scholarly journals Safety and Effectiveness of Apixaban, LMWH and Warfarin Among Venous Thromboembolism (VTE) Patients with Active Cancer: A Subgroup Analysis of VTE Risk Scale

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 327-327
Author(s):  
Alexander T Cohen ◽  
Allison Keshishian ◽  
Theodore Lee ◽  
Gail Wygant ◽  
Lisa Rosenblatt ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Cancer Patients ◽  
Lower Risk ◽  
Cancer Type ◽  
Advisory Committees ◽  
Recurrent Vte ◽  
High Risk Cancer ◽  
Similar Risk ◽  
Active Cancer

BACKGROUND: Cancer is an independent risk factor for venous thromboembolism (VTE) and the strongest predictor for all-cause and pulmonary embolism-related mortality. VTE risk is 4-7 times higher in cancer patients compared to non-cancer patients. Different cancer types are associated with different risk of VTE. Cancers of the brain, pancreas, stomach, liver, lungs, and kidneys-and hematologic malignancies-have the strongest association with the occurrence of VTE. The Khorana risk score based on the cancer type, blood counts, and body mass index is one of the VTE risk scales to predict the risk of thrombosis in cancer patients. This study evaluates the risk of major bleeding (MB), clinically relevant non-major (CRNM) bleeding, and recurrent VTE (non-fatal and fatal) among VTE patients with active cancer prescribed apixaban, low-molecular weight heparin (LMWH), or warfarin stratified by VTE risk. METHODS: A pooled study using four US commercial insurance claims databases identified VTE patients diagnosed with active cancer (defined as cancer diagnosis [any stage] or cancer treatment [chemotherapy, radiation, and cancer-related surgery] within 6 months before or 30 days after VTE diagnosis) who initiated apixaban, LMWH, or warfarin within 30 days following the first VTE event (01SEP2014-31MAR2018). Patients were followed to the earliest of: health plan disenrollment, death, index therapy discontinuation, switch to another anticoagulant, study end, or a maximum of 6 months. Stabilized inverse probability treatment weighting (IPTW) was used to balance treatment cohorts. A subgroup analysis using a modified Khorana VTE risk scale (cancer type only) was conducted. Patients were classified as very high risk (stomach, brain, or pancreas), high risk (lung, lymphoma, gynecologic, bladder, testicular, renal cell carcinoma), or other (all remaining cancer types) depending on their cancer type. Cox proportional hazard models were used to evaluate the risk of MB, CRNM bleeding, and recurrent VTE. The statistical significance (P<0.10) of the interaction between treatment and different levels of VTE risk was evaluated. RESULTS: After applying the selection criteria, 3,393 apixaban, 6,108 LMWH, and 4,585 warfarin patients were identified with mean ages of 65, 64, and 64 years, respectively. After IPTW, all patient characteristics were balanced. Among all VTE cancer patients after IPTW, 15% of patients had very high-risk cancer and 40% patients had high-risk cancer. In the main analysis, apixaban patients had a lower risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH. Warfarin patients had a similar risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH. Apixaban patients had a lower risk of recurrent VTE and a similar risk of MB and CRNM bleeding compared to warfarin (Figure). When stratifying by the VTE risk scale, study findings were generally consistent with the primary analysis and across the different subgroups. No significant interactions were observed for MB or CRNM bleeding (Figure). Two significant interactions were evident for recurrent VTE: apixaban trended towards a lower risk of recurrent VTE compared to LMWH across all three subgroups, but the magnitude of the difference was larger in the other cancer group vs. very high risk and high risk cancer groups. For warfarin vs. LMWH, different trends in recurrent VTE risk were observed among patients with different VTE risk levels (Figure). CONCLUSION: Across subgroups of VTE cancer patients with different VTE risk levels, apixaban had a lower risk of recurrent VTE compared to warfarin and a lower risk of MB, CRNM bleeding, and recurrent VTE compared to LMWH consistent with the overall results. Warfarin patients had a similar risk of MB and CRNM bleeding compared to LMWH. Further studies are needed to evaluate the role of anticoagulants in high-risk subgroups of VTE cancer patients. Figure Disclosures Cohen: Aspen: Consultancy, Speakers Bureau; CSL Behring: Consultancy; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ONO: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Leo Pharma: Consultancy; Guidepoint Global: Consultancy; TRN: Consultancy; Boehringer-Ingelheim: Consultancy, Speakers Bureau; UK Government Health Select Committee: Other: advised the UK Government Health Select Committee, the all-party working group on thrombosis, the Department of Health, and the NHS, on the prevention of VTE; Temasek Capital: Consultancy; Boston Scientific: Consultancy; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Lifeblood: Other: advisor to Lifeblood: the thrombosis charity and is the founder of the European educational charity the Coalition to Prevent Venous Thromboembolism; Johnson and Johnson: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Consultancy, Speakers Bureau; AbbVie: Consultancy; GLG: Consultancy; Medscape: Consultancy, Speakers Bureau; McKinsey: Consultancy; Navigant: Consultancy; Takeda: Consultancy; ACI Clinical: Consultancy. Keshishian:STATinMED Research: Other: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company and Pfizer Inc.. Lee:Pfizer Inc.: Employment, Equity Ownership. Wygant:Bristol-Myers Squibb Company: Employment. Rosenblatt:Bristol-Myers Squibb: Other: Stock Owner ; Bristol-Myers Squibb Company: Employment. Hlavacek:Pfizer Inc.: Employment. Mardekian:Pfizer Inc.: Employment. Wiederkehr:Pfizer Inc.: Employment. Sah:STATinMED Research: Other: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company and Pfizer Inc.. Luo:Pfizer Inc.: Employment.

scholarly journals Effectiveness and Safety of Apixaban, Low-Molecular-Weight Heparin, and Warfarin among Venous Thromboembolism Patients with Active Cancer: A U.S. Claims Data Analysis

2020 ◽  
Author(s):  
Alexander Cohen ◽  
Allison Keshishian ◽  
Theodore Lee ◽  
Gail Wygant ◽  
Lisa Rosenblatt ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Venous Thromboembolism ◽  
Lower Risk ◽  
Low Molecular Weight Heparin ◽  
Claims Data ◽  
Low Molecular Weight ◽  
Recurrent Vte ◽  
Similar Risk ◽  
Active Cancer

Abstract Background This study primarily evaluates the risk of recurrent venous thromboembolism (VTE) and major bleeding (MB) among patients with VTE and active cancer prescribed apixaban, low-molecular-weight heparin (LMWH), or warfarin, with claims data. Methods Four U.S. commercial insurance claims databases were used to identify patients with VTE and active cancer who initiated apixaban, LMWH, or warfarin within 30 days following the first VTE event. Stabilized inverse-probability treatment weighting (IPTW) was used to balance treatment cohorts. Cox proportional hazard models were used to evaluate risk of recurrent VTE and MB. Results All eligibility criteria were fulfilled by 3,393 apixaban, 6,108 LMWH, and 4,585 warfarin patients. After IPTW, all patient characteristics were balanced. When the follow-up was censored at 6 months, apixaban patients had a lower risk of recurrent VTE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.47–0.81) and MB (HR: 0.63; 95% CI: 0.47–0.86) versus LMWH. Apixaban patients had a lower risk of recurrent VTE (HR: 0.68; 95% CI: 0.52–0.90) and similar risk of MB (HR: 0.73; 95% CI: 0.53–1.00) versus warfarin. Warfarin patients had a similar risk of recurrent VTE (HR: 0.91; 95% CI: 0.72–1.15) and MB (HR: 0.87; 95% CI: 0.68–1.12) versus LMWH. The trends were similar for the entire follow-up; however, apixaban patients had a lower risk of MB versus warfarin patients. Conclusion Patients with VTE and active cancer who initiated apixaban had a lower risk of recurrent VTE and MB compared with LMWH patients. Apixaban patients also had a lower risk of recurrent VTE compared with warfarin patients.

scholarly journals Rate of Clonal Hematopoiesis in Patients with Venous Thromboembolism

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4297-4297
Author(s):  
Tamanna Haque ◽  
Arletta Lozanski ◽  
Tzyy-Jye Doong ◽  
Ying Huang ◽  
Rui Li ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Major Bleeding ◽  
Reference Sequence ◽  
Advisory Committees ◽  
Clonal Hematopoiesis ◽  
Male Patients ◽  
Baseline Characteristics ◽  
Recurrent Vte

Abstract Background Venous thromboembolism (VTE) is the third most common cardiovascular disease with an incidence over 1% in the elderly. About 50% of VTE is unprovoked, which is associated with higher rates of recurrent VTE and complications such as post-thrombotic syndrome. Clonal hematopoiesis (CH) refers to recurrent somatic mutations associated with hematologic malignancies that are present in otherwise healthy individuals. CH is more common with increased age, occurring in more than 10% of people over the age of 70 and has been associated with an increased risk of coronary artery disease. The rates of CH in patients with VTE or complications arising from this is not known. Methods Adult patients (age ≥ 18) with VTE were enrolled at the Ohio State University Thrombosis Clinic between 2017 and 2020. Clinical data was obtained at the time of routine clinic follow-up or ad hoc, and a research blood sample was collected with routine blood work. DNA extracted from peripheral blood mononuclear cells were analyzed for the presence of CH via error corrected next generation sequencing (NGS) using the Ion Gene Studio S5 System. A custom AmpliSeq panel IAH150087 was designed to detect CH, which included whole gene sequencing and hotspots in 25 common genes associated with myeloid malignancies, including DNMT3A, TET2, ASXL1, among others, with a sequencing depth of up to 50,000X. Data was collected and analyzed using Ion Torrent S5/GS-S5 Instrument with Torrent Suite 5.12.0 version. Final analysis of sequence data was performed using combination of software: Variant Caller v.5.12.10-1, IGV5.01 (0) and Ion Reporter v.5.12.3.0. The hg19 reference sequence was used to assess for deviation. CH was defined as a variable allele frequency ≥ 2%. Two sample t-test and chi-square test were used to compare patients with and without CH for continuous and categorical variables, respectively. Results A total of 167 patients are included the study. Median age is 60.3 years and 55% of patients are female. 80% of patients are white. The majority of patients have unprovoked VTE (81%); 23 patients (13.8%) have VTE associated with cancer. 84% of patients were treated with a direct oral anticoagulant. Over the median follow-up duration of 400 days, 7 patients had recurrent VTE and 19 patients had a total of 21 bleeding events (7 major bleeding and 14 clinically relevant non-major bleeding [CRNMB] by ISTH criteria). Overall, 22 patients (13.2%) have detectable CH. Patients with CH are significantly older than those without CH (mean age 70 vs 59, p <0.0001). There is a trend towards increased CH rate in male patients (17% of male patients vs 10% of female patients with CH). There are no other differences in baseline characteristics among patients with and without CH, including type or location of VTE or cancer status. Among the 144 VTE patients without cancer, the median age is 60 years old and the CH rate is also 13.2%. In this group, the mean age of patients with CH is 12 years older than those without CH (70.5 years vs 58.4 years, p <0.0001). No other significant baseline characteristics are noted. 30 distinct CH mutations are noted in these 22 patients. Most patients have a single gene mutation (77%). Gene mutations in DNMT3A are the most common (46%), followed by TET2 (13%), and PPM1D (10%) (see figure). Most mutations are missense (57%), followed by nonsense (30%) and insertion/deletion mutations (13%). One patient has a JAK2 V617F mutation without known history of myeloproliferative disease. 8 CH patients with serial samples collected over a median duration of 136 days (range 91 - 490 days) showed no significant change in CH clone size over time. Patients with CH have no differences in rates of recurrent VTE or arterial thrombosis compared to those without CH. Patients with CH have a trend towards increased rate of combined major bleeding and CRNMB events (23% vs 10%, p=0.14). Patients with CH also had a trend towards increased mean corpuscular volume (MCV) (mean 93.5 vs 90.7, p=0.13), although no other cytopenias or differences in complete blood count parameters were noted. Conclusion The CH rate in patients with VTE was not found to be much higher than what might be expected by age alone. We found no change in the CH rate after excluding cancer patients. A larger VTE population with age-matched controls will better determine the CH rate in patients with VTE. CH can be a consideration in designing future clinical VTE studies that assess bleeding risk. Figure 1 Figure 1. Disclosures Byrd: Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Newave: Membership on an entity's Board of Directors or advisory committees; Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria. Wang: Servier: Membership on an entity's Board of Directors or advisory committees; Leo Pharma: Research Funding.

scholarly journals Baseline Characteristics and Clinical Outcomes from the Cancer Associated Thrombosis - Patient Reported Outcomes with Rivaroxaban (COSIMO) Trial

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2161-2161
Author(s):  
Anthony Maraveyas ◽  
Jan Beyer-Westendorf ◽  
Agnes Yuet Ying Lee ◽  
Lorenzo G Mantovani ◽  
Yoriko De Sanctis ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Research Funding ◽  
Bleeding Event ◽  
Select Committee ◽  
Advisory Committees ◽  
Government Health ◽  
Patient Reported ◽  
Uk Government ◽  
Active Cancer

Background: Patients living with cancer who develop venous thromboembolism (VTE) have a high risk of VTE recurrence, and traditional anticoagulants (low molecular weight heparin [LMWH] or vitamin K antagonists [VKAs]) are associated with significant treatment burdens. Rivaroxaban is a direct oral anticoagulant (DOAC) that may provide a more convenient treatment option for these patients. Methods: The COSIMO study was a multinational, prospective, non-interventional, single-arm cohort study designed to collect real-world data on patient treatment satisfaction and outcomes associated with rivaroxaban treatment following ≥4 weeks of LMWH/VKA therapy for the treatment of acute VTE in patients with active cancer. Here, we report on the secondary objectives, which were to provide descriptive analyses of clinical characteristics and patterns of use of anticoagulant treatment, and to assess the safety and effectiveness of rivaroxaban in this patient population. Results: Overall, 505 patients were enrolled, and the qualifying venous thromboembolic event was deep vein thrombosis (DVT) only in 45.3% of patients, pulmonary embolism (PE) only in 37.2% of patients, DVT with PE in 9.7% of patients, and catheter-associated DVT in 7.5% of patients (Table). The majority of patients had solid tumors (n=449, 88.9%); 56 patients had hematological malignancies. The most common reasons to switch to rivaroxaban were patient preference/quality of life (n=310, 61.4%) and physician decision (n=174, 34.5%). A total of 150 (29.7%) patients were treated with concomitant chemotherapy and 79 (15.6%) received concomitant radiotherapy. Overall, 117 (23.2%) patients discontinued the study: 59 (11.7%) died, 21 (4.2%) withdrew consent, and 17 (3.4%) were lost to follow-up. 80.2% of patients were treated with rivaroxaban for at least 3 months, and most patients (78.6%) received rivaroxaban 20 mg once daily on study entry. Treatment-emergent adverse events (AEs) were reported: 312 (61.8%) patients had an AE (148 [29.3%] serious AEs), and 95 (18.8%) patients had a bleeding event reported, of which 18 (3.6%) patients had an adjudicated major bleeding event. Adjudicated symptomatic and incidental VTE recurrence occurred in 15 (3.0%) and 3 (0.6%) patients, respectively. Adjudicated other site thromboembolic events such as splanchnic or cerebral vein thromboses were symptomatic in 1 (0.2%) patient and incidental in 1 (0.2%) patient. Conclusions: Observed incidence rates of VTE and bleeding events in COSIMO were similar to previous studies of DOACs for VTE treatment in patients with active cancer (Young AM et al. J Clin Oncol 2018;36:2017; Raskob GE et al. N Engl J Med 2018;378:615). Study governance Bayer AG Funding The COSIMO study is funded by Bayer AG and Janssen Pharmaceuticals. Trial protocol number NCT02742623. Registered 19 April 2016. Documented approval from appropriate independent ethics committees/institutional review boards will be obtained for all participating centers prior to study start. Patients were asked to provide signed informed consent forms before joining the study. Few patients have yet completed the study, and so no data are available to share. Acknowledgements Editorial assistance was provided by Kate Weatherall of Chameleon Communications Int. Ltd. with funding from Bayer AG and Janssen Scientific Affairs, LLC. Disclosures Maraveyas: Bristol-Myers Squibb: Honoraria; Bayer AG: Honoraria, Research Funding; Pfizer: Honoraria. Beyer-Westendorf:Pfizer: Honoraria, Research Funding; Bayer HealthCare: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding. Lee:Pfizer: Consultancy, Honoraria; LEO Pharma: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding. Mantovani:Daiichi Sankyo: Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Bayer AG: Honoraria; Fondazione Charta: Consultancy; Pfizer: Honoraria. De Sanctis:Bayer US LLC: Employment, Equity Ownership. Abdelgawwad:Bayer AG: Employment. Fatoba:Bayer AG: Employment. Bach:Bayer AG: Employment. Cohen:Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithKline: Consultancy, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; ACI Clinical: Consultancy; CSL Behring: Consultancy; Aspen: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Lifeblood: Other: advisor to Lifeblood: the thrombosis charity and is the founder of the European educational charity the Coalition to Prevent Venous Thromboembolism; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ONO: Consultancy, Membership on an entity's Board of Directors or advisory committees; Boehringer-Ingelheim: Consultancy, Speakers Bureau; TRN: Consultancy; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy; Temasek Capital: Consultancy; Boston Scientific: Consultancy; Guidepoint Global: Consultancy; Medscape: Consultancy, Speakers Bureau; McKinsey: Consultancy; Navigant: Consultancy; UK Government Health Select Committee: Other: advised the UK Government Health Select Committee, the all-party working group on thrombosis, the Department of Health, and the NHS, on the prevention of VTE; Leo Pharma: Consultancy; GLG: Consultancy; Johnson and Johnson: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals Management of Secondary Prevention in Venous Thromboembolism: Use of Reduced Doses of Rivaroxaban and Apixaban in Extended Therapy

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Desiree Campoy ◽  
Katia Flores ◽  
Gonzalo Artaza ◽  
César A Velasquez ◽  
Tania Canals ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Secondary Prevention ◽  
Board Of Directors ◽  
Dose Reduction ◽  
Standard Dose ◽  
Control Group ◽  
Advisory Committees ◽  
The Mean ◽  
D Dimer

BACKGROUND After a standard anticoagulation period (3-6 months), the risk of venous thromboembolism recurrence (RVTER) needs to be considered. Such risk is higher in unprovoked events and patients with persistent risk factor. The increase of D-dimer (DD) levels during the therapy seems to be strongly associated to RVTER. The use of rivaroxaban 10 mg/day and apixaban 2.5mg/12h as an extended therapy (ET) after the standard anticoagulation period has been proven to be an effective strategy to prevent recurrence without increasing bleeding events. AIM To assess the effectiveness and safety of reduced doses of rivaroxaban and apixaban as ET in patients with RVTER and to compare their DD levels with those of a control group on anticoagulant therapy at a standard dose. METHODS From April 2016 to June 2020, we included patients with venous thromboembolism (VTE) who received ET with rivaroxaban and apixaban with/at reduced doses. Dose reduction was performed following the clinical algorithm of our unit (Fig. 1). The DD values were determined using HemosIl D-Dimer HS-500 and the cut-off value was established at 500 µg/L DD levels were compared with a control group of 235 patients with VTE who received ET with standard doses of anticoagulation. DD levels were measured at the time of diagnosis (D1), initiation of treatment (D2) and 3 months after treatment (D3). RESULTS From a total of 116 patients (65.5% women), 77.6% (n=90) received rivaroxaban 10 mg/24h and 22.4% received apixaban 2.5 mg/12h as an ET. The mean duration of the initial anticoagulant therapy was 12 +/- 8.8 months. The mean DD value prior to the ET was 388 µg/L. In this group, 63.8% (n=74) was an unprovoked VTE and 17.2% (20) had hereditary thrombophilia. The mean of follow-up time was 6.9 +/- 8.3 months. No recurrences of VTE were observed during the follow-up and only one major bleeding event was reported in a high-bleeding risk patient. We observed a progressive decrease of DD levels from the VTE diagnosis to the last visit, with D1, D2, and D3 values of 987 µg/L ± 324, 388 µg/L ± 134, and 288 µg/L ± 98, respectively. There were no differences in d-dimer concentrations between patients with reduce doses of rivaroxaban or apixaban and the control group with standard doses (D1: 85.6% vs 81%, p =0.22; D2: 10.2% vs 8.0%, p =0.14; and D3: 9.1% vs 9.5%, p =0.18). CONCLUSIONS Our data indicated that an ET strategy with reduced doses of rivaroxaban or apixaban is effective and safe. We did not observe significant differences in DD levels at follow-up compared to the control group receiving a standard dose of anticoagulation. Further studies are needed in order to select and standardize dose reduction criteria in secondary prevention. Figure 1 Disclosures Campoy: boehringer ingelheim: Consultancy; Daiichi Sankyo: Speakers Bureau. Sierra:Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Research Funding; Astellas: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead-Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Olivera:Daiichi Sankyo: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Boehringer Ingelheim: Consultancy, Speakers Bureau; BAYER: Consultancy.

Response to Treatment Among SF3B1 Mutated Myelodysplastic Syndromes (MDS): A Case-Control Study from the MDS Clinical Research Consortium (MDS CRC)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1697-1697 ◽  
Author(s):  
Rami S. Komrokji ◽  
Amy E. DeZern ◽  
Katrina Zell ◽  
Najla H. Al Ali ◽  
Eric Padron ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Lower Risk ◽  
Research Funding ◽  
Somatic Mutations ◽  
Response To Treatment ◽  
Wild Type ◽  
Advisory Committees ◽  
Baseline Characteristics ◽  
Matching Criteria

Abstract Introduction Somatic mutations in SF3B1 ,a gene encoding a core component of RNA splicing machinery, have been identified in patients (pts) with myelodysplastic syndrome (MDS). The SF3B1 mutation (MT) is more commonly detected in pts with ring sideroblasts (RS) morphology and is associated with favorable outcome. The pattern of response among SF3B1 mutated MDS pts to available treatment options, including erythropoiesis stimulating agents (ESA), hypomethylating agents (HMA) and lenalidomide is not known. The distinct underlying disease biology among such pts may alter response to treatment. Methods Pts treated at MDS CRC institutions with MT vs wild-type SF3B1 (WT) controls were matched 1:2. Matching criteria were age at diagnosis, year of diagnosis and International Prognostic Scoring System (IPSS) category at diagnosis. IPSS category was split into two groups (Low or Int-1 vs. Int-2 or High). Matching was performed using the R package by calculating a propensity score, which was then used to determine the two most similar WT SF3B1 patients for each SF3B1-mutated pt, without replacement. Additionally, to be included in the population, pts also had to have been treated with one of the following: ESAs, HMA, or lenalidomide. Response to treatment was evaluated by international Working Group criteria (IWG 2006) and classified as response if hematological improvement or better was achieved (HI+). Survival was calculated from date of treatment until date of death or last known follow-up, unless otherwise noted. Results: We identified 48 Pts with MT and 96 matched controls. Table 1 summarizes baseline characteristics comparing MT vs WT SF3B1 cohorts. SF3B1 MT was detected more often in association with RS, as expected. The majority of pts had lower-risk disease by IPSS and revised IPSS (IPSS-R). Pts with MT had higher platelets than controls. The most common concomitant somatic mutations observed were TET2 (30%), DNMT3A (21%), and ASXL1 (7%). Median follow-up time from diagnosis was 35 months (mo). Median overall survival (OS) from diagnosis was significantly longer for patients with SF3B1 MT (108.5 mo (68.8, NA)) than wild-type controls (28.3 mo (22.3, 36.4); p < 0.001). Patients with an SF3B1 MT had a decreased hazard of death (hazard ratio [HR]: 0.49 (95% confidence limits [95% CL]: 0.29, 0.84); p = 0.009) ESA was the first line therapy for 43 pts (88%) with MT and 55 WT Pts (56%). For ESA treated pts, 14 out 40 MT Pts responded (35%) compared to 9/56 among WT Pts (16%), p 0.032. Among those treated with HMA therapy, 5 out 21 (24%) MT pts responded compared to 11/46 (24%) WT Pts (p 0.99). Finally, for Pts treated with lenalidomide 4/16 (25%) and 4/21 (19%) responded among SF3B1 MT and WT Pts respectively, p 0.7. Conclusions SF3B1 somatic mutation in MDS is commonly associated with RS, lower risk disease, and better OS. Pts with SF3B1 mutation had higher response to ESA compared WT SF3B1. No difference in response to HMA or lenalidomide was observed compared to WT patients. Response rates to lenalidomide and HMA were low in both MT patients and controls. Biologically rational therapies are needed that target this molecular disease subset. Table 1. Baseline characteristics SF3B1 MT (n=48) SF3B1 WT (n=96) P value Age median 65 67 0.6 Gender male 29 (60%) 64(67%) 0.5 Race White 44/45 (98%) 83/90 (92%) 0.34 WHO classification RA RARS RCMD RARS-T Del5 q RAEB-I RAEB-II MDS-U MDS/MPN CMML 3 24 8 4 1 3 3 2 0 0 6 9 17 2 6 10 9 3 11 9 IPSS Low Int-1 Int-2 High 29 (60%) 16 (33%) 3 (6%) 0 21 (22%) 69 (72%) 4 (4%) 2 (2%) < 0.001 IPSS-R Very low Low Intermediate High Very High 15 (31%) 26 (54%) 5 (10%) 2 (4%) 0 11 (11%) 37 (39%) 26 (27%) 18 (19%) 4 (4%) <0.001 Lab values (mean) Hgb Platelets ANC myeloblasts 9.7 274 2.63 1 9.6 108 1.92 2 0.46 <0.001 0.04 0.05 Disclosures Komrokji: Novartis: Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding; Incyte: Consultancy; Pharmacylics: Speakers Bureau. Padron:Novartis: Speakers Bureau; Incyte: Research Funding. List:Celgene Corporation: Honoraria, Research Funding. Steensma:Incyte: Consultancy; Amgen: Consultancy; Celgene: Consultancy; Onconova: Consultancy. Sekeres:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; TetraLogic: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

Effectiveness and safety of apixaban, low-molecular weight heparin, and warfarin among high-risk subgroups of venous thromboembolism patients with active cancer

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Cohen ◽  
A Keshishian ◽  
T Lee ◽  
G Wygant ◽  
L Rosenblatt ◽  
...  
Keyword(s):  
High Risk ◽  
Cancer Treatment ◽  
Lower Risk ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Funding Source ◽  
Event Type ◽  
Recurrent Vte ◽  
Similar Risk ◽  
Active Cancer

Abstract Background Cancer-associated venous thromboembolism (VTE) carries a high risk for recurrent events and major bleeding (MB) which further increases among some high-risk subgroups of patients. Purpose This study evaluates recurrent VTE and MB among VTE patients with active cancer within 6 months of initiating apixaban, low-molecular weight heparin (LMWH), or warfarin stratified by cancer type, cancer treatment, and VTE characteristics. Methods Four US commercial insurance claims databases were pooled to identify VTE patients with active cancer (defined as ≥1 claim with cancer diagnosis [any stage] or cancer treatment [chemotherapy, radiation, and cancer-related surgery] within 6 months before to 30 days after VTE diagnosis). Patients who initiated apixaban, LMWH, or warfarin within 30 days following the first VTE event (01SEP2014–31MAR2018) were included. Treatment cohorts were balanced using stabilized inverse probability treatment weighting (IPTW). Cox proportional hazards models were used to estimate hazard ratios of recurrent VTE and MB for each subgroup stratification: metastatic diagnosis, cancer treatment, chemotherapy, upper and lower gastrointestinal (GI) cancer, and VTE event type (PE with or without deep vein thrombosis [DVT] versus DVT only). Statistical significance (P&lt;0.10) of the interaction between the subgroup strata and outcomes were evaluated. Results A total of 3,393 apixaban, 6,108 LMWH, and 4,585 warfarin patients were identified with a mean follow-up of 105–166 days across cohorts. After IPTW, all patient characteristics were balanced. In the overall population, apixaban had a lower risk of recurrent VTE and MB vs. LMWH. Warfarin had a similar risk of recurrent VTE and MB vs. LMWH. Apixaban had a lower risk of recurrent VTE and a similar risk of MB vs. warfarin (Figure). Analyses stratified by metastatic diagnosis, cancer treatment, chemotherapy, VTE event type, and GI cancer show generally consistent results across the subgroups (most of the p values for interaction &gt;0.10) and with the overall population. There was a significant interaction in cancer treatment strata: apixaban trended towards a lower risk of MB vs. LMWH with or without cancer treatment; however, patients without cancer treatment had a larger difference vs. patients with cancer treatment. Two significant interactions were observed in metastatic diagnosis strata: apixaban and warfarin had a lower risk of recurrent VTE vs. LMWH in patients without a metastatic diagnosis whereas apixaban and warfarin had similar risk of recurrent VTE vs. LMWH in patients with a metastatic diagnosis (Figure). Conclusion Across these high-risk subgroups of VTE cancer patients, apixaban generally had a lower risk of recurrent VTE and MB vs. LMWH and lower risk of recurrent VTE compared to warfarin. Warfarin patients generally had a similar risk of recurrent VTE and MB vs. LMWH. The findings are generally consistent with the overall population results. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Pfizer Inc. and Britstol-Myers Squibb Company.

scholarly journals Validation of the Ottawa Score in Cancer Patients with Venous Thromboembolism. the Predicare Cohort Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 167-167 ◽  
Author(s):  
Guy Meyer ◽  
Celine Chapelle ◽  
Philippe Girard ◽  
Florian Scotté ◽  
Anne Lamblin ◽  
...  
Keyword(s):  
Cohort Study ◽  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Research Funding ◽  
Advisory Committees ◽  
Patients With Cancer ◽  
Recurrent Vte ◽  
Support Research

Introduction Venous thromboembolism (VTE) is a difficult to treat condition in patients with cancer with a persisting risk of recurrent VTE during anticoagulant treatment with low-molecular weight heparin (LMWH). Recent data suggest that direct oral anticoagulants (DOACS) are associated with a lower risk of recurrence but a higher risk of bleeding in these patients. Predicting the risk of recurrent VTE with LMWH may help to select the best treatment option. We conducted a prospective multicenter observational cohort study in cancer patients with VTE treated with tinzaparin for 6 months in order to validate the Ottawa score (NCT03099031) and search for additional risk of recurrent VTE. The Ottawa score is composed of 5 variables, female sex (+1), lung cancer (+1), breast cancer (-1) cancer stage 1 (-2) and previous DVT (+1). A score ≤0 is associated with a low risk of recurrent VTE. Methods Adult cancer patients with recent diagnosis of documented symptomatic or incidental VTE (deep vein thrombosis (DVT) or pulmonary embolism (PE) treated with tinzaparin for 6 months were included in the study. The primary endpoint was the recurrence of symptomatic or asymptomatic VTE within the first 6 months of treatment with tinzaparin. Other endpoints were symptomatic recurrent VTE, major bleeding, heparin induced thrombocytopenia (HIT), all-cause mortality within 3 and 6 months. All events were adjudicated by a Central Adjudication Committee. Time-to-event outcomes were estimated by the Kalbfleisch and Prentice method to take into account the competing risk of death. Cumulative incidences were presented with corresponding 95% confidence interval (95% CI). To validate the Ottawa score, the area under the curve (AUC) and its 95% CI were calculated on receiver operating characteristic (ROC) curve analysis; the most discriminant cut-off was then determined by calculating the Youden index. Univariate and multivariate analyses were performed to identify additional predictive factors of recurrent VTE to those included in the Ottawa score using the Fine and Gray method and adjusted on factors included in the Ottawa score. Hazard ratio and their 95% CI were calculated. Results A total of 409 patients were included and analyzed on an intention-to-treat basis; the median age was 68 years and 51% of patients were males. 60.4% of patients had a PE (with or without DVT) .64% received chemotherapy at inclusion or in the month before inclusion. Lung (31.3%) and digestive track (18.3%) cancers were the most common cancer types and 67.0% had stage IV cancers. According to Ottawa score, 58% of patients were classified at high clinical probability of recurrence (score ≥ 1). During the 6 months treatment period, 23 patients had a recurrent VTE, yielding a cumulative incidence of 6.1% (95% CI 4.0-9.3) with a median time for recurrent VTE of 33 days. The recurrence rate of VTE was estimated to 7.8% (95% CI 4.9-12.5) for patients classified at high risk of recurrence according to the Ottawa score (score ≥ 1) compared to 3.8% (95%CI 1.6-8.9) for other patients (Ottawa score &lt; 1). AUC of the Ottawa score was 0.60 (95% CI 0.55-0.65). In multivariable analysis, none of the potential risk factors for recurrent VTE was significantly associated with recurrent VTE at 6 months. During the 6 months treatment period, 15 patients had a major bleeding and 2 patients experienced a HIT. At 3 and 6 months, 104 and 144 patients had died yielding a cumulative incidence of 26.1%, (95% CI 21.8-30.4) and 37.8% (95% CI 32.8-42.9), respectively. The main cause of death was underlying cancer. Conclusion In this prospective cohort of patients with cancer receiving LMWH for VTE, the Ottawa score did not accurately predict recurrent VTE. No other clinical predictor of recurrent VTE was identified in this study. Disclosures Meyer: Bayer: Other: travel support; LEO pharma: Other: travel support, Research Funding; SANOFI: Other: travel support, Research Funding; BMS-Pfizer: Other: travel support, Research Funding; Boehringer Ingelheim: Research Funding. Girard:Leo Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: travel support. Scotté:LEO Pharma A/S: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria, Research Funding, Speakers Bureau; Tesaro: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Research Funding, Speakers Bureau; MSD: Honoraria, Research Funding, Speakers Bureau; Pierre Fabre Oncology: Honoraria, Research Funding, Speakers Bureau. Lamblin:Leo Pharma: Employment. Laporte:Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boston scientific: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Leo-Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Boehringer-Ingelheim: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Imetelstat Treatment Leads to Durable Transfusion Independence (TI) in RBC Transfusion-Dependent (TD), Non-Del(5q) Lower Risk MDS Relapsed/Refractory to Erythropoiesis-Stimulating Agent (ESA) Who Are Lenalidomide (LEN) and HMA Naive

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 463-463 ◽  
Author(s):  
David P. Steensma ◽  
Uwe Platzbecker ◽  
Koen Van Eygen ◽  
Azra Raza ◽  
Valeria Santini ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Lower Risk ◽  
Research Funding ◽  
Employment Equity ◽  
Advisory Committees ◽  
Transfusion Independence ◽  
Equity Ownership ◽  
Grade 3 ◽  
Rbc Transfusion

Abstract BACKGROUND: Patients with TD lower-risk (LR)-MDS relapsed or refractory to ESA have limited treatment options. Imetelstat is a first-in-class telomerase inhibitor that targets cells with short telomere lengths and active telomerase, characteristics observed in some MDS patients. IMerge is an ongoing global study of imetelstat in RBC TD patients with LR-MDS (IPSS Low or Int-1). In the first 32 patients enrolled, 8-week TI rate was 34%, with 24-week TI of 16%, and HI-E of 59%. The most frequently reported adverse events were reversible grade ≥3 cytopenias (Fenaux et al EHA 2018 Abstr S1157). Higher response rates were observed in patients (n=13) who were LEN and HMA naïve without del(5q). We report here results in an additional 25 LEN and HMA naïve patients without del(5q), with longer term follow-up of the 13 initial patients meeting the same criteria. METHODS: IMerge is a phase 2/3 trial (NCT02598661) that includes LR-MDS patients with a high transfusion burden (≥4 units / 8 weeks) who are relapsed/refractory to ESA or have sEPO >500 mU/mL. The additional 25 were required to be LEN and HMA naïve and lack del(5q). Imetelstat 7.5 mg/kg was administered IV every 4 weeks. In addition to the key endpoints noted above, secondary endpoints include safety, time to and duration of TI. Biomarkers are also being explored, including telomerase activity, hTERT, telomere length, and genetic mutations. RESULTS: Overall, for the 38 LEN/HMA naïve and non-del(5q) patients, median age was 71.5 years and 66% were men. 63% of patients were IPSS Low and 37% Int-1. Median prior RBC transfusion burden was 8.0 (range 4-14) U, and 71% had WHO 2008 RARS or RCMD-RS. 9/37 (24%) patients with evaluable sEPO levels had baseline level >500 mU/mL. As of July 2018, with a median follow-up of 25.8 months for the initial 13 patients, and 5.2 months for the 25 recently included patients, the 8-week RBC-TI rate was 37% (14/38). Durability of 24-week TI responses was demonstrated, with a median duration of 10 months and the longest ongoing response now >2 years. Among the patients achieving durable TI, all showed a Hb rise of ≥3.0 g/dL compared to baseline during the transfusion-free interval. Response rates were similar in RARS/RCMD-RS (33% [9/27]) and other patients (27% [3/11]), and those with baseline EPO levels >500 mU/mL (33% [3/9]) and ≤500 mU/mL (32% [9/28]). Reversible grade ≥3 neutropenia and thrombocytopenia were each reported in 58% of the patients. Liver function test (LFT) elevations were mostly grade 1/2. Reversible grade 3 LFTelevations were observed in 3 (8%) patients on study. An independent Hepatic Review Committee deemed the observed LFT elevations were not imetelstat-related hepatic toxicities. SUMMARY / CONCLUSIONS: In this cohort of 38 non-del(5q) LR-MDS patients with a high RBC transfusion burden who were ESA relapsed/refractory and naïve to LEN/HMA, single-agent imetelstat yielded a TI rate of 37%, with a median duration of 10 months and limited side effects. Durable responses were characterized by transfusion independence >24 weeks and accompanied by Hb rise. Updated data will be presented. Disclosures Steensma: Takeda: Consultancy; Syros: Research Funding; Otsuka: Membership on an entity's Board of Directors or advisory committees; Onconova: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Janssen: Consultancy, Research Funding; H3 Biosciences: Research Funding; Celgene: Research Funding; Amphivena: Membership on an entity's Board of Directors or advisory committees; Acceleron: Consultancy. Platzbecker:Celgene: Research Funding. Van Eygen:Janssen: Consultancy, Research Funding; Roche: Research Funding; Amgen: Research Funding. Raza:Kura Oncology: Research Funding; Onconova: Research Funding, Speakers Bureau; Celgene: Research Funding; Novartis: Speakers Bureau; Geoptix: Speakers Bureau; Janssen: Research Funding; Syros: Research Funding. Santini:Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; AbbVie: Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Research Funding. Germing:Celgene: Honoraria, Research Funding; Janssen: Honoraria; Novartis: Honoraria, Research Funding. Font:Celgene: Membership on an entity's Board of Directors or advisory committees. Samarina:Janssen: Research Funding. Díez-Campelo:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Bussolari:Janssen: Employment, Equity Ownership. Sherman:Janssen: Employment, Equity Ownership. Sun:Janssen: Employment, Equity Ownership. Varsos:Janssen: Employment, Equity Ownership. Rose:Janssen: Employment, Equity Ownership. Fenaux:Roche: Honoraria; Otsuka: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding.

scholarly journals Frequency of Venous Thromboembolism in 6513 Patients with COVID-19: A Retrospective Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-22
Author(s):  
Mark Crowther ◽  
David A. Garcia ◽  
Jason Hill ◽  
Bryan Savage ◽  
Shira Peress ◽  
...  
Keyword(s):  
Emergency Department ◽  
Mechanical Ventilation ◽  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Traditional Approach ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Increased Risk ◽  
Anticoagulant Prophylaxis

Background: Patients infected with coronavirus 2 (SARS-CoV-2) appear to be at increased risk for venous thromboembolism (VTE), especially if they become critically ill with coronavirus disease 2019 (COVID-19). Some centers have reported very high rates of thrombosis despite anticoagulant prophylaxis. Methods: The electronic health record (EHR) of a New Orleans-based health system was searched for all patients with PCR-confirmed SARS-CoV-2 infection who were either admitted to hospital or treated and discharged from an emergency department between March 1 and May 1, 2020. From this cohort, patients with confirmed VTE (either during or after their hospital encounter) were identified by administrative query of the EHR. Results: Between March 1, 2020 and May 1, 2020, 6,153 patients with COVID-19 were identified; 2,748 of these patients were admitted, while 3,405 received care exclusively through the emergency department. Data on patient outcomes were determined up until and including May 21, 2020. In total, 637 patients required mechanical ventilation and 206 required renal replacement therapy. Within the hospitalized cohort, the overall mortality rate was 24.5% and VTE occurred in 86 patients (3.1%). In the 637 patients who required mechanical ventilation at some point during their hospital stay, 45 developed VTE (7.2%). After a median follow-up of 14.6 days, VTE had been diagnosed in 3 of the 2,075 admitted who were discharged alive (0.14%). Conclusions: Among 6,153 patients with COVID-19 who were hospitalized or treated in emergency departments, we did not find evidence of unusually high VTE risk. Pending further evidence from prospective, controlled trials, our findings support a traditional approach to primary VTE prevention in patients with COVID-19. Disclosures Crowther: Precision Biologicals: Membership on an entity's Board of Directors or advisory committees; Hemostais Reference Laboratories: Honoraria; Pfizer: Speakers Bureau; CSL Behring: Speakers Bureau; Alnylam: Divested equity in a private or publicly-traded company in the past 24 months; Servier Canada: Membership on an entity's Board of Directors or advisory committees; Diagnostica Stago: Speakers Bureau; Asahi Kasei: Membership on an entity's Board of Directors or advisory committees.

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