Current management of cancer-associated venous thromboembolism in patients with thrombocytopenia: a retrospective cohort study

AbstractOptimal management of venous thromboembolism (VTE) in cancer patients with thrombocytopenia is uncertain. We described current management and clinical outcomes of these patients. We retrospectively included a cohort of cancer patients with acute VTE and concomitant mild (platelet count 100,000–150,000/mm3), moderate (50,000–99,000/mm3), or severe thrombocytopenia (< 50,000/mm3). Univariate and multivariate logistic regression analyses explored the association between different therapeutic strategies and thrombocytopenia. The incidence of VTE and bleeding complications was collected at a 3-month follow-up. A total of 194 patients of whom 122 (62.89%) had mild, 51 (26.29%) moderate, and 22 (11.34%) severe thrombocytopenia were involved. At VTE diagnosis, a full therapeutic dose of LMWH was administered in 79.3, 62.8 and 4.6% of patients, respectively. Moderate (OR 0.30; 95% CI 0.12–0.75), severe thrombocytopenia (OR 0.01; 95% CI 0.00–0.08), and the presence of cerebral metastasis (OR 0.06; 95% CI 0.01–0.30) were independently associated with the prescription of subtherapeutic LMWH doses. Symptomatic VTE (OR 4.46; 95% CI 1.85–10.80) and pulmonary embolism (OR 2.76; 95% CI 1.09–6.94) were associated with the prescription of full therapeutic LMWH doses. Three-month incidence of VTE was 3.9% (95% CI 1.3–10.1), 8.5% (95% CI 2.8–21.3), 0% (95% CI 0.0–20.0) in patients with mild, moderate, and severe thrombocytopenia, respectively. The corresponding values for major bleeding and mortality were 1.9% (95% CI 0.3–7.4), 6.4% (95% CI 1.7–18.6), 0% (95% CI 0.0–20.0) and 9.6% (95% CI 5.0–17.4), 48.2% (95% CI 16.1–42.9), 20% (95% CI 6.6–44.3). In the absence of sound evidence, anticoagulation strategy of VTE in cancer patients with thrombocytopenia was tailored on an individual basis, taking into account not only the platelet count but also VTE presentation and the presence of cerebral metastasis.

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Predicting recurrences or major bleeding in cancer patients with venous thromboembolism

Thrombosis and Haemostasis ◽

10.1160/th08-02-0125 ◽

2008 ◽

Vol 100 (09) ◽

pp. 435-439 ◽

Cited By ~ 105

Author(s):

Javier Trujillo-Santos ◽

José Nieto ◽

Gregorio Tiberio ◽

Andrea Piccioli ◽

Pierpaolo Micco ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Cancer Diagnosis ◽

Major Bleeding ◽

Bleeding Complications ◽

Vein Thrombosis ◽

Recurrent Pulmonary Embolism ◽

Acute Venous Thromboembolism ◽

Deep Vein

SummaryCancer patients with acute venous thromboembolism (VTE) have an increased incidence of recurrences and bleeding complications while on anticoagulant therapy. Methods RIETE is an ongoing registry of consecutive patients with acute VTE. We tried to identify which cancer patients are at a higher risk for recurrent pulmonary embolism (PE), deep vein thrombosis (DVT) or major bleeding. Up to May 2007, 3, 805 cancer patients had been enrolled in RIETE. During the first three months of follow-up after the acute, index VTE event, 90 (2.4%) patients developed recurrent PE, 100 (2.6%) recurrent DVT, 156 (4.1%) had major bleeding. Forty patients (44%) died of the recurrent PE,46 (29%) of bleeding. On multivariate analysis, patients aged <65 years (odds ratio [OR]: 3.0; 95% confidence interval [CI]: 1.9–4.9), with PE at entry (OR: 1.9; 95% CI: 1.2–3.1), or with <3 months from cancer diagnosis to VTE (OR: 2.0; 95% CI: 1.2–3.2) had an increased incidence of recurrent PE. Those aged <65 years (OR: 1.6; 95% CI: 1.0–2.4) or with <3 months from cancer diagnosis (OR: 2.4; 95% CI: 1.5–3.6) had an increased incidence of recurrent DVT. Finally, patients with immobility (OR: 1.8; 95% CI: 1.2–2.7), metastases (OR: 1.6; 95% CI: 1.1–2.3), recent bleeding (OR: 2.4; 95% CI: 1.1–5.1), or with creatinine clearance <30 ml/ min (OR: 2.2; 95% CI: 1.5–3.4), had an increased incidence of major bleeding. With some variables available at entry we may identify those cancer patients withVTE at a higher risk for recurrences or major bleeding.

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GECAT - German Evaluation of Cancer Associated Thrombosis: A Prospective Register Trial for Patients with Active Cancer and Venous Thromboembolism (VTE) in Berlin

Blood ◽

10.1182/blood-2019-128166 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4969-4969

Author(s):

Marianne Sinn ◽

Christiane Pollich ◽

Hanno Riess ◽

Sven Bischoff ◽

Piet Habbel ◽

...

Keyword(s):

Venous Thromboembolism ◽

General Practitioner ◽

Cancer Patients ◽

Research Funding ◽

Bleeding Complications ◽

Newly Diagnosed ◽

Anticoagulation Treatment ◽

Daily Care ◽

Active Cancer

Background: National and international guidelines for the diagnosis and treatment of cancer associated venous thromboembolism (CAT) recommend anticoagulation treatment for 3 to 6 months and a re-evaluation for resumption depending on the individual risk of every patient. In CAT low molecular weight heparin (LMWH) was estimated to be the most effective and safest treatment option in 2015. However, it remains unclear how cancer patients with VTE were (treated in clinical daily care in Germany. In former register trials, the specific characteristics of individual cancer patients were insufficiently characterized and inadequately discussed. Special aspects of daily care are lacking in most publications. Methods: The GECAT register was set up for Berlin´s two main hospital companies Charité-Universitaetsmedizin Berlin and Vivantes, (both covering about 50 % of the hospital beds in Berlin) to document prospectively patients with a newly diagnosed VTE . Patients with the diagnosis of cancer within 2 years prior to the VTE got basis documentation by a physician after informed consent. A follow up of these patients was scheduled after 3 and 6 months per telephone interview. Points of interest were: kind and location of the VTE event, diagnostic procedures, drug and dosage of initial and follow-up anti-coagulation treatment, relapse of VTE or bleeding complications, serious adverse events, mortality, and date and reason for determination of anticoagulation. Primary objective was to evaluate the treatment reality of patients with cancer associated VTE in clinical daily practice. Results: Between May 2015 and May 2017, 382 patients (pts) with active cancer within the last 2 years and newly diagnosed VTE gave consent to this register trial. 193 (50.5%) were female, median age was 65 years (range 19-89). For 133 pts (34.8%), VTE was the primary reason for admission at hospital, 34.3% were referred by their oncologist, 13,6% by their general practitioner, 15,5% by other treating physicians and 36.6% directly via the emergency department. 182 pts (47.6%) had pulmonary embolism, 268 pts (70.2%) had venous thrombosis and 18,6%71 pts (18.6%) had both. The most common cancer sites were lung (n=57, 14,9%), gynecological (n=44, 11,5%), colorectal (n=40, 10,5%) and pancreatic cancer (n=33 8,6%); 204 pts (56%) with solid tumors presented with stage IV diseases; 60 pts (15.7%) had hematological malignancies. 279 pts (73%) received anticancer treatments at the time of diagnosis of VTE. 148 (38.7%) pts died in the 6 months study period (20 pts died in hospital after admission, 90 pts within the first 3 months and 38 pts within the 6 months follow up). Initially, the majority of pts (n=350; 91.6%) was treated with LMWH. After discharge from hospital 78.7% remained on LMWH and 12.7% were treated with direct oral anticoagulants (DOACs). After 3 months 64.9% of pts received LMWH and 26.1% DOACs; after 6 months 48.4% LMWH and 44% DOACs. Responsible for the anticoagulation treatment decisions was mostly the oncologist (58%), followed by the general practitioner (26.3%) and other physicians (15,7%) . During the initial hospital stay, 2.6% of pts had a bleeding complication and 0.8% were diagnosed with a progress of VTE. At 6 months follow up, 6.4% reported bleeding complications and 2.4% recurrent VTE. Conclusion: The GECAT register trial gives new and clinically relevant information about the clinical daily care practice of cancer patients with newly diagnosed VTE in Berlin, Germany. The treating oncologist is in most cases responsible for the treatment. Disclosures Sinn: LEO: Research Funding; Bayer Healthcare AG: Research Funding; Servier: Honoraria, Research Funding; Astra Zeneca: Honoraria, Research Funding; Amgen: Honoraria; Sanofi: Honoraria. Scholz:Celgene: Consultancy; GILEAD: Consultancy, Speakers Bureau; Roche: Consultancy; Janssen-Cilag: Consultancy; Hexal: Consultancy; Novartis: Consultancy; Pfizer: Speakers Bureau; Takeda: Consultancy; Daiichi Sankio: Consultancy. Klamroth:Bayer, Biomarin, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, SOBI, Takeda: Consultancy; Bayer, Novo Nordisk, SOBI: Research Funding.

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Abstract 16543: Severe Thrombocytopenia is Common in Adults Undergoing Venoarterial Extracorporeal Membrane Oxygenation and is Predictive of Hemorrhage

Circulation ◽

10.1161/circ.142.suppl_3.16543 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Tia C Kohs ◽

Vikram Raghunathan ◽

Patricia Liu ◽

Ramin Amirsoltani ◽

Michael Oakes ◽

...

Keyword(s):

Overall Survival ◽

Logistic Regression ◽

Platelet Count ◽

Extracorporeal Membrane Oxygenation ◽

Clinical Implications ◽

Severe Thrombocytopenia ◽

Multivariate Logistic Regression ◽

Membrane Oxygenation ◽

Increased Risk ◽

Va Ecmo

Introduction: Extracorporeal membrane oxygenation (ECMO) is used to provide circulatory support and facilitate gas exchange via cardiopulmonary bypass. The relationship between ECMO and the incidence of severe thrombocytopenia (platelet count <50 x 10 9 /L) and subsequent clinical consequences are ill defined. We aimed to identify the risk factors for the development of thrombocytopenia and its clinical implications. Methods: This is a single-center retrospective cohort study of adults who received venoarterial (VA) ECMO. We examined consecutive platelet counts while on ECMO. Univariate logistic regression was used to determine if mean platelet count, platelet count range, or severe thrombocytopenia were predictors of overall survival, hemorrhage and thrombosis. A multivariate logistic regression model was used to identify factors that contribute to the development of the aforementioned patient outcomes. Results: In our cohort, 33 patients were included with a mean age of 55 years and duration of ECMO of 5.9 days. All patients received heparin, 33.3% received antiplatelet therapy and 45.5% developed severe thrombocytopenia. In univariate, analysis the development of severe thrombocytopenia increased the odds of major bleeding by 450% (OR 5.500, 95% CI 1.219 - 24.813, P -value 0.027), and the odds of surviving hospitalization decreased 84.1% (OR 0.159, 95% CI 0.033 - 0.773, P -value 0.023). Multivariate logistic regression controlling for additional clinical variables found no significant association between the development of severe thrombocytopenia and rates of thrombosis, hemorrhage, or overall survival. Platelet count decreased over time while on ECMO. Conclusions: Nearly half of the patients requiring VA-ECMO developed severe thrombocytopenia, which was associated with an increased risk of hemorrhage and in-hospital mortality. Additional studies are required to clarify the clinical implications of severe thrombocytopenia in ECMO patients.

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Physicians’ Choice in Using Internet and Fax for Patient Recruitment and Follow-up in a Randomized Controlled Trial

Methods of Information in Medicine ◽

10.1055/s-0038-1633867 ◽

2004 ◽

Vol 43 (03) ◽

pp. 268-272 ◽

Cited By ~ 5

Author(s):

S. Morita ◽

T. Fukui ◽

J. Sakamoto ◽

M. Rahman

Keyword(s):

Randomized Controlled Trial ◽

Odds Ratio ◽

Controlled Trial ◽

Data Entry ◽

Regression Analyses ◽

Multivariate Logistic Regression ◽

Web Based ◽

Randomized Controlled ◽

The Web

Summary Objective: To examine the physicians’ preference between Web and fax-based remote data entry (RDE) system for an ongoing randomized controlled trial (RCT) in Japan. Methods: We conducted a survey among all the collaborating physicians (n = 512) of the CASE-J (Candesartan Antihypertensive Survival Evaluation in Japan) trial, who have been recruiting patients and sending follow-up data using the Web or a fax-based RDE system. The survey instrument assessed physicians’ choice between Web and fax-based RDE systems, their practice pattern, and attitudes towards these two modalities. Results: A total of 448 (87.5%) responses were received. The proportions of physicians who used Web, fax, and the combination of these two were 45.9%, 33.3% and 20.8%, respectively. Multivariate logistic regression analyses revealed that physicians 55 years or younger [odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1-3.3] and regular users of computers (OR = 4.2, 95% CI = 2.1-8.2) were more likely to use the Web-based RDE system. Conclusions: This information would be useful in designing an RCT with a Web-based RDE system in Japan and abroad.

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A Screening and Intervention Program Reducing Mortality and Serious Morbidity Associated with Neonatal Alloimmune Thrombocytopenia.

Blood ◽

10.1182/blood.v106.11.1232.1232 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1232-1232

Author(s):

Jens Kjeldsen-Kragh ◽

Mette K. Killie ◽

Geir Tomter ◽

Elzbieta Golebiowska ◽

Helene Pedersen ◽

...

Keyword(s):

Platelet Count ◽

Intervention Program ◽

Human Platelet ◽

Fetal Brain ◽

University Hospital ◽

Severe Thrombocytopenia ◽

Platelet Antigen ◽

Human Platelet Antigen ◽

Alloimmune Thrombocytopenia

Abstract Background: Neonatal alloimmune thrombocytopenia (NAIT) is most frequently caused by antibodies against the human platelet antigen (HPA) 1a. The objective of the present study was to identify HPA 1a negative women, and to offer them an intervention program aimed to reduce morbidity and mortality of NAIT. Methods: A total of 100,448 pregnant women were HPA 1 typed. The HPA 1a negative women were screened for anti-HPA 1a, which was quantified when present. Immunized women were referred to a university hospital for clinical follow-up, including ultrasonographic examination of the fetal brain. Caesarean section was performed 2–4 weeks prior to term with platelets from HPA 1bb donors reserved for immediate transfusion if petechiae were present and/or if platelet count was < 35 × 109/L. Results: Of all women typed 2.1% were HPA 1a negative. Anti-HPA 1a was detected in 210 of 1,990 HPA 1a negative women. A total of 170 pregnancies in 154 HPA 1a negative women were managed according to the intervention program. These women gave birth to 161 HPA 1a positive children of whom 55 had severe thrombocytopenia (<50 × 109/L) including two with ICH. There were no intrauterine deaths. In 13 previously published prospective studies comprising 131,465 women of whom 2,290 were HPA 1a negative, there were 10 cases with severe NAIT-related complications (3 intrauterine deaths and 7 neonates with ICH), which are significantly higher than in our study (p < 0.05). Conclusions: The screening and intervention program seems to reduce mortality and serious morbidity associated with NAIT.

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Platelet Cut-Off For Anticoagulant Therapy In Cancer Patients With Venous Thromboembolism and Thrombocytopenia: An Expert Opinion Based On RAND/UCLA Appropriateness Method (RAM)

Blood ◽

10.1182/blood.v122.21.581.581 ◽

2013 ◽

Vol 122 (21) ◽

pp. 581-581 ◽

Cited By ~ 5

Author(s):

Giorgia Saccullo ◽

Marco Marietta ◽

Monica Carpenedo ◽

Valerio De Stefano ◽

Anna Falanga ◽

...

Keyword(s):

Molecular Weight ◽

Platelet Count ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Low Molecular Weight Heparin ◽

Expert Panel ◽

Fixed Dose ◽

Low Molecular Weight ◽

Best Management ◽

Expected Benefits

Abstract Introduction Cancer-related Venous Thromboembolism (VTE) requires treatment with Low Molecular Weight Heparin (LMWH), which is more effective and safer than warfarin; however, the risk of major hemorrhage still remains clinically relevant (up to 5%). This rate is even higher in case of impaired hemostasis, such as during thrombocytopenia (due to myelosuppression or chemo-therapy) where the bleeding risk is directly related to the platelet count level. At the present, the best management of adult patients with acute or non-acute cancer-related VTE during thrombocytopenia is uncertain. Objective To develop a consensus about the platelet cut-off for a safe LMWH administration in cancer patients with acute (lasting < 1 month) or non-acute VTE and thrombocytopenia, based on RAND/UCLA Appropriateness Method (RAM). Materials and methods A systematic review of the literature was performed via electronic databases (MEDLINE, EMBASE, and Cochrane Library Central Registry). Topics and research terms were: cancer, venous thromboembolism, platelets, risk of bleeding, anticoagulant drugs, low-molecular-weight heparin, and treatments. The main study outcomes were rates of VTE (first event, recurrence, and catheter-related DVT), major and minor bleeding, thrombocytopenia, and death. A panel of experts was identified; the literature review and the list of indications were sent to all members of this panel. For each indication, the panel members rated the benefit-to-harm ratio of the procedure on a scale of 1 to 9, where 1 means that the expected harms greatly outweigh the expected benefits, and 9 means that the expected benefits greatly outweigh the expected harms. A middle rating of 5 means either that the harms and benefits are about equal or that the rater cannot make the judge for the patient described in the indication. The working group comprised 9 hematologists expert in thrombosis and haemostasis (G.S., M.M., M.C., V.D.S., A.F., A.F., F.R., A.T., S.S.) including two methodologists (G.S. and M.M.) and one coordinator (S.S.). Consensus Development the RAND was construed identifying 3 platelet count cut-offs (i.e., PLT >50.000 <100.000 µL; PLT >30.000 <50.000 µL; PLT <30.000 µL) and 3 doses of LMWH (weight adjusted fixed-dose, prophylactic dose, and half of the weight adjusted fixed-dose) by administering 13 questions to the experts. Results The panel of expert reached the following consensus: 1. Cancer patients with acute VTE and a platelet count <100.000 µL - >50.000 should receive full therapeutic dose LMWH ; 2. In cases of non-acute VTE with platelet count <100.000 µL - >50.000, the dose of LMWH should be reduced to 75% of the full dose; 3. In cancer patients with acute VTE and platelet count <50.000 - >30.000 µL, the LMWH dose should be reduced to 50% of the full therapeutic dose; 4. In case of non-acute VTE and a platelet count <50.000 µL - >30.000, the expert panel considers uncertain a treatment with a reduced dose to 50% or a low dose (i.e. 4.000 IU anti-FXa/d); 5. In case of platelet count below 30.000 µL, the expert panel agreed to suspend LMWH both in acute and non-acute VTE. Conclusions This is the first expert opinion based on RAM to establish the safe platelet cut-off to administer LMWH therapy in cancer patients affected by acute and non-acute VTE. The present panel of experts suggests as appropriate the use of dose-adjusted LMWH according to platelets count. Further investigations by means of well designed prospective clinical trials are needed to establish the best management of cancer-related VTE in patients with thrombocytopenia. Disclosures: Rodeghiero: Amgen, GSK: Honoraria; Amgen, Eisai, GSK, LFB, Suppremol: Membership on an entity’s Board of Directors or advisory committees.

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Severe Thrombocytopenia Does Not Increase Bleeding Complications in Patients Undergoing Bronchoscopy

Blood ◽

10.1182/blood.v124.21.4293.4293 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4293-4293

Author(s):

Lakshminarayanan Nandagopal ◽

Muthu Veeraputhiran ◽

Tania Jain ◽

Ayman Soubani ◽

Charles A. Schiffer

Keyword(s):

Platelet Count ◽

Renal Dysfunction ◽

Platelet Transfusion ◽

Conflicts Of Interest ◽

Bleeding Complications ◽

British Thoracic Society ◽

Severe Thrombocytopenia ◽

Platelet Counts ◽

Number Of Patients ◽

Platelet Transfusions

Abstract Introduction Prophylactic platelet transfusions are often performed prior to bronchoscopy or broncho-alveolar lavage (BAL) to prevent bleeding in thrombocytopenic patients. There is a paucity of data to validate this approach, with a platelet transfusion threshold of <50,000/mm3 largely based on expert opinion. We conducted a retrospective study on the incidence of bleeding complications in thrombocytopenic patients undergoing bronchoscopy. Methods We identified 150 consecutive patients with platelet counts <100,000/mm3 who underwent bronchoscopy and/or BAL from January 2009 to May 2014 at our institution. Bronchoscopies performed in patients with frank hemoptysis and trans-bronchial lung biopsy procedures were excluded. Patient characteristics, underlying diagnosis, platelet count prior to bronchoscopy, administration of platelet transfusions and bronchoscopy details were recorded. Factors affecting bleeding risk including presence of renal dysfunction (defined as BUN >30 and/or Cr>2.0) and coagulation studies (PT, PTT, INR) were identified. The British Thoracic Society guidelines1 were used to categorize bleeding as a result of bronchoscopy. Data were analyzed using descriptive statistics. Results The median age was 59 years (range 27-90), with two-thirds of patients (63%) being male. One hundred and seventeen (78%) patients had underlying malignancy and 55 (37%) had thrombocytopenia related to malignancy. Fellows and residents under the supervision of a bronchoscopy certified attending performed all but 4 of the bronchoscopies. Infection (40%) was the primary indication for bronchoscopy with BAL performed in 127 (85%) patients. Fifty-eight of 89 (65%) patients with baseline platelet counts <50,000/mm3 received prophylactic transfusions compared to 8% of those with platelet counts >50,000/mm3. The platelet count did not rise to >50,000//mm3 in many transfused patients. Seventy patients (47%) had counts <50,000/mm3 and eighty patients (53%) had counts >50,000/mm3 at the time of bronchoscopy. 49% were receiving immunosuppressive medications, 45% had renal dysfunction and 8% had INR >1.5. Bloody lavage that resolved spontaneously without continuous suctioning (Grade 0) was observed in 9 (6%) patients. Bleeding that required continuous suctioning but then resolved spontaneously (Grade 1) was noted in 1 patient with a platelet count of 61,000/mm3. Of 10 total bleeding events, 7 occurred in patients who were intubated. Two additional patients with platelet counts of 30,000/mm3 and 53,000/mm3 had diffuse alveolar hemorrhage, which was present before bronchoscopy. “Old” blood and blood clots were observed in 6 patients. Discussion The low incidence of bleeding complications from bronchoscopy +/- BAL even in patients with platelet counts <30,000/mm3 (3 episodes in 31 patients, all grade 0) demonstrates that bronchoscopy can be safely done in severely thrombocytopenic patients. Adopting a lower threshold for prophylactic transfusions could save a considerable number of platelet units and translate into significant cost savings and decreased risk of transfusion-related complications. Table 1 Platelet count, transfusion history and bleeding complications during bronchoscopy Platelet count at the time of bronchoscopy Number (n) and percentage (%) of patients who underwent bronchoscopy Number of patients who received prior platelet transfusion Bleeding during bronchoscopy n % 0-15,000/mm3 9 6% (9/150) 5 Grade 0=1 pt 16-29 22 15% 16 Grade 0=2 pts 30-39 17 11% 9 Grade 0=1 pt 40-49 22 15% 9 Grade 0=3 pts 50-75 44 29% 14 Grade 1=1 pt 76-100 36 24% 10 Grade 0=2 pts Total 150 63 Grade 0=9 pts, Grade 1=1 pt. 1.Du Rand IA, Blaikley J, Booton R, et al. British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults: accredited by NICE. Thorax. 2013:68 Suppl 1:i1-i44 Disclosures No relevant conflicts of interest to declare.

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Risk of Recurrent Venous Thromboembolism and Bleeding in Patients with Cancer Associated Thrombosis

Blood ◽

10.1182/blood-2020-142805 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 18-18

Author(s):

Doaa Attia ◽

Xuefei Jia ◽

Mailey L Wilks ◽

Barbara Tripp ◽

Christopher D'Andrea ◽

...

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Major Bleeding ◽

Research Funding ◽

Cleveland Clinic ◽

Treatment Groups ◽

Recurrent Venous Thromboembolism ◽

Recurrent Vte ◽

Cancer Associated Thrombosis

Background: The treatment paradigm for cancer associated thrombosis (CAT) has evolved over recent years from using low molecular weight heparin (LMWH) to direct oral anticoagulants (DOACs). Some randomized trials suggest decreased rates of recurrent venous thromboembolism (VTE) in CAT patients treated with DOACs compared to LMWH but also reported increased rates of bleeding. The Cleveland Clinic Taussig Cancer Center has been treating cancer thrombosis in a centralized CAT clinic since 2014. Here we report our rates of bleeding and recurrent VTE in cancer patients treated with anticoagulation. Methods: We prospectively followed cancer patients referred to our clinic from 8/2014-10/2019. A total of 1548 patients were referred to the clinic, of whom 462 were diagnosed with an acute VTE. VTE events, including deep venous thrombosis, pulmonary embolism, and visceral thrombosis, were noted. The comparison of bleeding rates (defined using ISTH criteria for major and clinically relevant non major bleeding, CRNMB) among treatment groups (LMWH vs DOACs) was examined using chi-square test. Rate of recurrent VTE was analyzed using a competing model in which death was treated as a competing risk. Results: The study population comprised 462 patients with acute VTE with a mean age of 62.67±12.23 and 51.8 % males. Of these, 234 (52.9%) received LMWH, 161(36.4%) received DOACs, and 47 (10.6%) received other agents including warfarin for initial anticoagulation. Overall, the 6-month, 1 year, and 2-year VTE recurrence rate was 5.9%, 6.6%, 7.9%, respectively. Recurrent VTE rates were similar for LMWHs, DOACs and other agents (P>0.05). Of 368 patients for whom follow-up data was available, 74 (16.7%) had bleeding event , of which 25 (33.8%) had major bleeding and 49 (66.4%) had CRNMB at 6 month follow-up with no difference across three treatment groups (p=0.56). Conclusion: In this real-world practice setting, rates of recurrent VTE and bleeding were similar for DOACs and LMWH suggesting that with careful patient selection the concern for higher bleeding with DOACs in cancer patients can be safely overcome. Disclosures McCrae: Momenta Pharmaceuticals: Consultancy; Novartis: Honoraria; Rigel: Consultancy; Dova: Consultancy. Khorana:Merck: Research Funding; Medscape: Honoraria; Leo Pharma: Honoraria; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Pharmacyclics: Honoraria; Array: Other: Research funding (to institution); Janssen: Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; BMS: Honoraria, Research Funding; Leap: Research Funding.

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Incidence, Characteristics and Outcomes of Patients with Cancer-Associated Venous Thromboembolism: A Retrospective Matched-Pair Analysis

Blood ◽

10.1182/blood-2018-99-113420 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2516-2516

Author(s):

Piyanuch Kongtim ◽

Dhosaporn Charoenjit ◽

Supawee Saengboon ◽

Hataiwan Ratanabunjerdkul

Keyword(s):

Venous Thromboembolism ◽

Cancer Patients ◽

Cancer Diagnosis ◽

Cumulative Incidence ◽

Hematologic Malignancies ◽

Matched Pair ◽

Advanced Stage ◽

Vein Thrombosis ◽

Patients With Cancer

Abstract Introduction Cancer and its treatments are well-recognized risk factors for the development of venous thromboembolism (VTE). The occurrence of VTE has been associated with an increased mortality in patients with cancer. Here we retrospectively reviewed the incidence and characteristics of cancer-associated thrombosis (CAT) in a large cohort of cancer patients treated at our institution as well as compared treatment outcomes of this group of patients with a 1:1 matched pair group of cancer patients without CAT. Methods Data of consecutive patients, 18 years of age or older, with a newly diagnosis of both hematologic malignancies or solid tumors who diagnosed and treated either as an inpatient or outpatient setting at our institution between 2011 to 2015 were included in this analysis. Patients who received anticoagulants for the purpose of either prophylaxis or treatment within 2 weeks before cancer diagnosis and who did not have a histologically confirmed a cancer diagnosis or complete follow up data were excluded from the study. To compare the outcomes of cancer patients with and without CAT, cancer patients who did not experience CAT were randomly selected from the same database and were matched individually (1:1) to cancer patients with CAT based on age, sex, cancer type and stage (limited or advanced) to form a matched cohort of patients as control. Primary outcome was cumulative incidence of CAT at 6 months and 1 year after cancer diagnosis, while incidence of recurrent VTE, major and minor bleeding, relapse, non-relapse mortality (NRM), overall survival (OS) and progression-free survival (PFS) were analyzed as secondary outcomes. CAT was defined as at least 1 site of venous thrombosis confirmed by imaging results, which occurred anytime after the initial diagnosis, during the treatment or follow-up. Results Total 2,291 newly diagnosed cancer patients (633 patients with hematologic malignancies and 1,658 patients with solid cancers) with a median age of 58 years (range 18-93 years) were included in the analysis. CAT was developed in 83 patients (52 females and 31 males) with a median age of 61 year (range 20-85 years). The cumulative incidence of CAT at 6 months and 1 year was 2.7% and 3.4%, respectively. The median time from cancer diagnosis to the diagnosis of CAT was 3.2 months (range 1- 62 months). Sites of VTE were deep vein thrombosis in extremities (N=46; 55.4%), pulmonary embolism (N=6; 7.2%), splanchnic vein thrombosis (N=9; 10.8%) and cerebral venous sinus thrombosis (N=5, 6%). Seventeen patients (20%) developed more than 1 site of VTE. Sixty-nine (83%) cases with CAT were diagnosed in patients with hematologic malignancies including 35, 22 and 12 cases with lymphoma, acute leukemia and myeloproliferative neoplasms, respectively. Overall the incidence was 10.9% in hematologic malignancies and 0.8% in solid tumors. The majority of the CAT cases occurred in advanced stage cancers (66 patients; 79.5%) while 13 cases (15.7%) were diagnosed during ambulatory chemotherapy treatment. None of the patients with CAT received prophylaxis anticoagulant during cancer treatment or follow up period. Characteristics of patients with CAT are summarized in Table 1. Of 83 patients with CAT, 66 patients were treated with anticoagulants, while inferior vena cava filter was used in 8 patients (9.6%). The cumulative incidence of total bleeding events at 1 year was 21.1% whereas cumulative incidence of major bleeding was 6.8%. The cumulative incidence of recurrent thrombosis at 1 year was 8.3%. Cancer patients who developed CAT had both a significantly higher NRM (26.2% vs. 13% at 1 year, p=0.004) (Figure 1A) and relapse rate (63.3% vs. 43.5% at 5 years, p=0.002) (Figure 1B) when compared with control group, which resulted in a significantly lower 5-year OS (24.9% vs. 62.7%; p<0.0001) (Figure 1C) and PFS (16.9% vs. 46%; p<0.0001) (Figure 1D). Advanced stage cancer and development of CAT were associated with poor OS in a multivariable analysis with HR of 6.9 (95%CI 2.7-17.7) and 3.9 (95%CI 2.2-7.0), respectively. Both factors also independently predicted risk of relapse with HR of 4.6 (95%CI 1.8-11.6, p=0.001) and 3.4 (95%CI 1.7-6.8, p<0.0001), respectively. Conclusions Development of CAT is associated with an increased NRM, relapse rate and poor survival in patients with cancer. Effective strategies to prevent CAT especially in high-risk cancer patients are needed to help improve outcomes. Disclosures No relevant conflicts of interest to declare.

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Clinical and Genomic Factors Are Predictive of Response and Prognostic of Progression-Free Survival in Patients with Waldenström Macroglobulinemia Treated with Ibrutinib

Blood ◽

10.1182/blood-2019-125069 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2823-2823

Author(s):

Jorge J. Castillo ◽

Joshua Gustine ◽

Maria Demos ◽

Andrew Keezer ◽

Kirsten Meid ◽

...

Keyword(s):

Logistic Regression ◽

Serum Albumin ◽

Research Funding ◽

Regression Models ◽

Progression Free Survival ◽

Regression Analyses ◽

Multivariate Logistic Regression ◽

Free Survival ◽

Lower Odds

Introduction: The Bruton tyrosine kinase inhibitor ibrutinib is the only FDA approved therapy for the treatment of symptomatic Waldenstrom macroglobulinemia (WM), and has been associated with high response rates and durable progression-free survival (PFS). Factors associated with depth of response and PFS duration are not well established. We performed a retrospective study aimed at identifying predictive and prognostic factors in WM patients treated with ibrutinib. Methods: We included consecutive patients with a diagnosis of WM treated with ibrutinib monotherapy evaluated at the Dana-Farber Cancer Institute since January 2012 through March 2019. Patients with Bing-Neel syndrome (WM involving the central nervous system) were excluded. Baseline clinical and laboratory characteristics were gathered. MYD88 and CXCR4 mutations were assessed using polymerase chain reaction assays and Sanger sequencing. Responses at 6 months were assessed using criteria from IWWM3. PFS was defined as the time from ibrutinib initiation until last follow-up, death or progression. Univariate and multivariate logistic regression models were fitted for partial response (PR) and very good partial response (VGPR) at 6 months, and Cox proportional-hazard regression models were fitted for PFS. Results: A total of 252 patients were included in our analysis. Selected baseline characteristics include: age ≥65 years (60%), hemoglobin <11.5 g/dl (68%), platelet count <100 K/uL (12%), albumin <3.5 g/dl (39%), b2-microglobulin ≥3 mg/l (70%), serum IgM level ≥7,000 mg/dl (6%), bone marrow involvement ≥60% (54%), previously untreated for WM (33%), time to ibrutinib <3 years (46%). MYD88 L265P and CXCR4 mutations were detected in 98% and 38% of patients, respectively. At 6 months, 71% of patients obtained PR, and 17% VGPR. Multivariate logistic regression analyses showed higher odds of PR at 6 months for hemoglobin <11.5 g/dl (78% vs. 56%; OR 2.8, 95% CI 1.1-6.9; p=0.03) and serum albumin <3.5 g/dl (90% vs. 66%; OR 3.2, 95% CI 1.0-10; p=0.045), while CXCR4 mutations associated with lower odds (44% vs. 82%; OR 0.15, 95% CI 0.06-0.37; p<0.001). Multivariate logistic regression analyses showed higher odds of VGPR at 6 months for b2-microglobulin ≥3 mg/l (21% vs. 3%; OR 3.3, 95% CI 1.1-10; p=0.04) and lower odds for serum IgM level ≥4,000 mg/dl (9% vs. 23%; OR 0.3, 95% CI 0.1-0.8; p=0.02). The median follow-up was 30 months, and the median PFS has not yet been reached. The 5-year PFS rate was 60% (95% CI 48-69%). In the multivariate Cox regression analysis, worse outcomes were seen with CXCR4 mutations (5-year PFS: 45% vs. 71%; HR 2.8, 95% CI 1.4-5.8; p=0.004) and serum albumin <3.5 g/dl (5-year PFS: 36% vs. 68%; HR 2.7, 95% CI 1.3-5.5; p=0.007). A novel PFS risk score was designed using CXCR4 mutational status and serum albumin (Figure), which divided patients into 3 distinct groups: low risk (no risk factors: 43%; 5-year PFS 81%), intermediate risk (1 risk factor: 46%; 5-year PFS 51%) and high risk (2 risk factors: 11%; median PFS 25 months). The PFS difference between groups was statistically significant (p<0.001). The PFS risk score showed consistent results when evaluating previously treated and untreated patients, as well as patients on and off clinical trials. Conclusion: Serum albumin and CXCR4 mutations emerge as important factors predictive of PR at 6 months and also prognostic of PFS in WM patients treated with ibrutinib. A novel PFS stratification tool that separates patients into 3 risk groups was established and would need further validation. Figure Disclosures Castillo: Abbvie: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; TG Therapeutics: Research Funding. Hunter:Janssen: Consultancy. Treon:Pharmacyclics: Research Funding; BMS: Research Funding; Janssen: Consultancy.

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