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Thromboembolism in Patients with Metastatic Renal Cell Carcinoma Treated with Immunotherapy - Beyond the Abstract

Cancer-associated thrombosis is a condition where patients with active cancer have a higher risk of deep vein thrombosis and pulmonary embolism compared to the general population.1-2 Compared to patients without cancer-associated thrombosis, patients with cancer-associated thrombosis have a higher morbidity and mortality, higher likelihood of cancer progression, and increased health care costs.2-4 Specifically, patients with renal cell carcinoma have a higher risk of thromboembolism compared to other cancers, due to a higher risk of thromboembolism, both anatomically through direct invasion of the IVC, as well as biologically through overexpression of tissue factor on cancer cells and cancer cell microparticles.1,5


Despite their elevated risk, patients with GU cancers have been unrepresented in the thromboprophylaxis trials. A metanalysis of 7 thromboprophylaxis trials showed only 2% of those enrolled had GU primaries.6 Another unique factor about renal cell carcinoma is that cancer itself is immune sensitive. Over the last decade, immunotherapy has become a part of the standard of care. However, It is unknown whether immunotherapy further increases the hypercoagulable state in this already high-risk population.

Unlike immunotherapy, the association between chemotherapy and cancer-associated thrombosis has been explored. The Khorana score was designed as a model to predict which patients were at high risk to develop venous thromboembolism at chemotherapy initiation in the ambulatory setting. Currently, it is recommended that with a Khorana score ≥ 2 should be started on thromboprophylaxis prior to treatment initiation. Whether the Khorana score can be used to risk-stratify patients more likely to develop cancer-related thrombosis on immunotherapy is unclear.

Thus, we studied the relationship between thromboembolism and immunotherapy in patients with advanced renal cell carcinoma with the objective to identify the incidence and associated outcomes of venous and arterial thromboembolic events in patients with advanced renal cell carcinoma treated with immunotherapy, as well as the potential association between the Khorana score and thromboembolism in this cohort.

Our study showed that patients with advanced renal cell carcinoma treated with immunotherapy had a 1-year thromboembolic incidence of 10%, which is higher than that is reported in the literature for patients with renal cell carcinoma, not on immunotherapy. There were no independent risk factors for thromboembolism development found. In particular, the Khorana score was not predictive of thromboembolic events. However, both thromboembolism and a Khorana score > 2 were associated with poor survival. Furthermore, TE is associated with the risk of treatment delay, hospitalization. Overall, our study showed a high incidence of thromboembolism in patients with renal cell carcinoma on immunotherapy.

While we have an excellent risk model, the Khorana score, for those who are initiating chemotherapy. We do not have a similar predictive model for immunotherapy

This is a large knowledge gap as thromboembolic events are associated with poor outcomes.

Thus, further studies are needed to refine a predictive model for patients at risk for thromboembolic events.

Written by: Iris Y. Sheng MD1, Shilpa Gupta MD2, Chandana A. Reddy MS3, Dana Angelini MD2, Pauline Funchain MD2, Tamara A. Sussman MD4, Joseph Sleiman MD5, Moshe C. Ornstein MD MA2, Keith McCrae MD2, Alok A. Khorana MD2

  1. Department of Medicine, Beth Israel Lahey Mt. Auburn Hospital, Boston, MA, USA.
  2. Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA.
  3. Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
  4. Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
  5. Department of Gastroenterology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

References:

  1. Navi BB, Reiner AS, Kamel H, Iadecola C, Okin PM, Elkind MSV, et al. Risk of Arterial Thromboembolism in Patients With Cancer. J Am Coll Cardiol. 2017;70:926–38.
  2. Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med. 2006;166:458–64.
  3. Khorana AA, Dalal MR, Lin J, Connolly GC. Health care costs associated with venous thromboembolism in selected high-risk ambulatory patients with solid tumors undergoing chemotherapy in the United States. Clin Outcomes Res CEOR. 2013;5:101–8.
  4. Zareba P, Duivenvoorden WCM, Pinthus JH. Thromboembolism in Patients with Bladder Cancer: Incidence, Risk Factors and Prevention. Bladder Cancer Amst Neth. 4:139–47.
  5. Wojtukiewicz MZ, Zacharski LR, Memoli VA, Kisiel W, Kudryk BJ, Rousseau SM, et al. Fibrinogen-fibrin transformation in situ in renal cell carcinoma. Anticancer Res. 1990;10:579–82.
  6. Perlmutt et al ASCO Annual Meeting 2020.Abstract e17115

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