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Thromb Haemost 2022; 122(09): 1594-1602
DOI: 10.1055/a-1777-4006
Stroke, Systemic or Venous Thromboembolism

Outcome of Cancer-Associated Venous Thromboembolism Is More Favorable among Patients with Hematologic Malignancies than in Those with Solid Tumors

Ramón Lecumberri
1   Hematology Service, Clínica Universidad de Navarra, Pamplona, Spain
2   CIBERCV, Instituto de Salud Carlos III, Madrid, Spain
,
Pedro Ruiz-Artacho 
3   Department of Internal Medicine, Clínica Universidad de Navarra, Madrid, Spain
4   CIBERES, Instituto de Salud Carlos III, Madrid, Spain
,
Inna Tzoran
5   Hematology Service, Rambam – Health Care Campus, Haifa, Israel
,
Benjamin Brenner
5   Hematology Service, Rambam – Health Care Campus, Haifa, Israel
,
Dominique Farge-Bancel
6   Internal Medicine Unit UF (04), Hôpital Saint-Louis, AP-HP, Université de Paris, Paris, France
,
Cihan Ay
7   Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
,
Vladimir Rosa
8   Department of Internal Medicine, Hospital Universitario Virgen de Arrixaca, Murcia, Spain
,
Iria Francisco
9   Department of Internal Medicine, Hospital Universitari de Girona Dr. Josep Trueta, Gerona, Spain
,
Luis Manuel Hernández-Blasco
10   Department of Pneumonology, Hospital General Universitario de Alicante, ISABIAL, UMH, Alicante, Spain
,
Javier Trujillo-Santos
11   Department of Internal Medicine, Hospital General Universitario Santa Lucía, Universidad Católica de Murcia, Murcia, Spain
,
Manuel Monreal
12   Department of Internal Medicine, Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain
13   Department of Thromboembolic Disease, Faculty of Health Sciences, UCAM - Universidad Católica San Antonio de Murcia, CIBERES, Instituto de Salud Carlos III, Madrid, Spain
,
the RIETE Investigators › Author Affiliations Funding None.
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Abstract

Background The natural history of patients with hematologic cancer and venous thromboembolism (VTE) has not been consistently evaluated. We aimed to compare the rates of symptomatic recurrent VTE, major bleeding, or death during anticoagulant therapy in patients with VTE associated with hematologic versus solid cancers.

Methods Consecutive patients with active cancer recruited in RIETE were evaluated. Their baseline characteristics, treatments, and outcomes during the course of anticoagulation were compared. Univariate and multivariate competing-risk analyses were performed.

Results As of December 2020, 16,694 patients with cancer and VTE were recruited. Of these, 1,062 (6.4%) had hematologic cancers. Hematologic patients were less likely to initially present with pulmonary embolism (46 vs. 55%) and more likely with upper extremity deep vein thrombosis (25 vs. 18%). They also were more likely to have severe thrombocytopenia at baseline (5.6 vs. 0.7%) or to receive chemotherapy (67 vs. 41%). During the course of anticoagulation (median, 150 vs. 127 days), 1,071 patients (6.4%) developed VTE recurrences, 806 (4.8%) suffered major bleeding, and 4,136 (24.8%) died. Patients with hematologic cancers had lower rates of recurrent VTE (rate ratio [RR]: 0.73; 95% confidence interval [CI]: 0.56–0.95), major bleeding (RR: 0.72; 95% CI: 0.53–0.98), or all-cause death (RR: 0.49; 95% CI: 0.41–0.57) than those with solid cancers. Patients with multiple myeloma showed the best outcomes.

Conclusion Patients with hematologic cancers, particularly multiple myeloma, and VTE had better outcomes than those with solid cancers. These findings are relevant for the interpretation of previous clinical trials and the design of future studies.

Keywords

bleeding - cancer - hematologic malignancies - recurrence - venous thromboembolism

Author Contributions

R.L., I.T., and M.M. were involved in study design, data collection and interpretation, writing and critical review, and final approval of the manuscript. J.T-.S. was involved in data collection, data analysis and interpretation, writing and critical review, and final approval of the manuscript. All other authors were involved in data collection and interpretation, writing and critical review, and final approval of the manuscript.


* A full list of the RIETE investigators is included in [Supplementary Appendix A].


Supplementary Material



Publication History

Received: 05 November 2021

Accepted: 08 February 2022

Accepted Manuscript online:
21 February 2022

Article published online:
13 June 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Timp JF, Braekkan SK, Versteeg HH, Cannegieter SC. Epidemiology of cancer-associated venous thrombosis. Blood 2013; 122 (10) 1712-1723
    CrossrefPubMedGoogle Scholar
  • 2 Prandoni P, Lensing AW, Piccioli A. et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100 (10) 3484-3488
    CrossrefPubMedGoogle Scholar
  • 3 Sørensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000; 343 (25) 1846-1850
    CrossrefPubMedGoogle Scholar
  • 4 Alam AU, Karkhaneh M, Sun HL, Wu C. Survival patterns among venous thromboembolism patients with hematologic malignancies in Alberta, Canada from 2003 to 2015. Thromb Res 2021; 199: 59-66
    CrossrefPubMedGoogle Scholar
  • 5 Farge D, Frere C, Connors JM. et al; International Initiative on Thrombosis and Cancer (ITAC) advisory panel. 2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol 2019; 20 (10) e566-e581
    CrossrefPubMedGoogle Scholar
  • 6 Key NS, Khorana AA, Kuderer NM. et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol 2020; 38 (05) 496-520
    CrossrefPubMedGoogle Scholar
  • 7 Muñoz Martín AJ, Gallardo Díaz E, García Escobar I. et al. SEOM clinical guideline of venous thromboembolism (VTE) and cancer (2019). Clin Transl Oncol 2020; 22 (02) 171-186
    CrossrefPubMedGoogle Scholar
  • 8 Mahé I, Chidiac J, Bertoletti L. et al; RIETE investigators. The clinical course of venous thromboembolism may differ according to cancer site. Am J Med 2017; 130 (03) 337-347
    CrossrefPubMedGoogle Scholar
  • 9 Lee AY, Levine MN, Baker RI. et al; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003; 349 (02) 146-153
    CrossrefPubMedGoogle Scholar
  • 10 Lee AYY, Kamphuisen PW, Meyer G. et al; CATCH Investigators. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial. JAMA 2015; 314 (07) 677-686
    CrossrefPubMedGoogle Scholar
  • 11 Raskob GE, van Es N, Verhamme P. et al; Hokusai VTE Cancer Investigators. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med 2018; 378 (07) 615-624
    CrossrefPubMedGoogle Scholar
  • 12 Young AM, Marshall A, Thirlwall J. et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol 2018; 36 (20) 2017-2023
    CrossrefPubMedGoogle Scholar
  • 13 Agnelli G, Becattini C, Meyer G. et al; Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med 2020; 382 (17) 1599-1607
    CrossrefPubMedGoogle Scholar
  • 14 Lecumberri R, Ruiz-Artacho P, Trujillo-Santos J. et al; RIETE Investigators. Management and outcomes of cancer patients with venous thromboembolism presenting with thrombocytopenia. Thromb Res 2020; 195: 139-145
    CrossrefPubMedGoogle Scholar
  • 15 Lecumberri R, Alfonso A, Jiménez D. et al; RIETE investigators. Dynamics of case-fatalilty rates of recurrent thromboembolism and major bleeding in patients treated for venous thromboembolism. Thromb Haemost 2013; 110 (04) 834-843
    PubMedGoogle Scholar
  • 16 Martin DO, Austin H. Exact estimates for a rate ratio. Epidemiology 1996; 7 (01) 29-33
    CrossrefPubMedGoogle Scholar
  • 17 Kekre N, Connors JM. Venous thromboembolism incidence in hematologic malignancies. Blood Rev 2019; 33: 24-32
    CrossrefPubMedGoogle Scholar
  • 18 Mulder FI, van Es N, Kraaijpoel N. et al. Edoxaban for treatment of venous thromboembolism in patient groups with different types of cancer: results from the Hokusai VTE Cancer study. Thromb Res 2020; 185: 13-19
    CrossrefPubMedGoogle Scholar
  • 19 Zakai NA, Walker RF, MacLehose RF, Adam TJ, Alonso A, Lutsey PL. Impact of anticoagulant choice on hospitalized bleeding risk when treating cancer-associated venous thromboembolism. J Thromb Haemost 2018; 16 (12) 2403-2412
    CrossrefPubMedGoogle Scholar
  • 20 De Stefano V, Ruggeri M, Cervantes F. et al. High rate of recurrent venous thromboembolism in patients with myeloproliferative neoplasms and effect of prophylaxis with vitamin K antagonists. Leukemia 2016; 30 (10) 2032-2038
    CrossrefPubMedGoogle Scholar
  • 21 Lee SE, Jeon YW, Yoon JH. et al. Clinical outcomes of venous thromboembolism with dalteparin therapy in multiple myeloma patients. Thromb Res 2015; 136 (05) 974-979
    CrossrefPubMedGoogle Scholar
  • 22 Eichinger S, Heinze G, Kyrle PA. D-dimer levels over time and the risk of recurrent venous thromboembolism: an update of the Vienna prediction model. J Am Heart Assoc 2014; 3 (01) e000467
    CrossrefPubMedGoogle Scholar
  • 23 Muñoz FJ, Mismetti P, Poggio R. et al; RIETE Investigators. Clinical outcome of patients with upper-extremity deep vein thrombosis: results from the RIETE Registry. Chest 2008; 133 (01) 143-148
    CrossrefPubMedGoogle Scholar
  • 24 Ageno W, Haas S, Weitz JI. et al. Upper extremity DVT versus lower extremity DVT: perspectives from the GARFIELD-VTE registry. Thromb Haemost 2019; 119 (08) 1365-1372
    Article in Thieme ConnectPubMedGoogle Scholar