Metastatic renal cell carcinoma (mRCC) is associated with a high risk of thromboembolism (TE).
We investigated whether immunotherapy (IO) increases the hypercoagulable state in this high-risk population.
Patients with mRCC treated with IO between 1 January 2015 and 31 December 2019 at the Cleveland Clinic were identified. Cumulative incidence analysis calculated TE rates over time and Gray's test determined differences in TE rates among groups. The Kaplan-Meier method estimated survival, while Cox proportional hazard regression evaluated the impact of TE on OS.
Of 351 patients, 75% were men with clear cell mRCC (81%) and International Metastatic Renal Cell Carcinoma (IMDC) intermediate- to poor-risk disease (77%). Patients received single-agent IO (52%), doublet IO (31%), or IO with non-IO therapy (17%). The median number of IO doses was 8 (range 1-81). At a median follow-up of 12.8 months, 12% of patients (n = 43) had a TE event (venous n = 37 [11%], arterial n = 6 [2%]). The cumulative TE incidence at 6 months was 4.4% (95% confidence interval [CI] 2.6-6.9) and 9.8% (95% CI 6.8-13.4) at 12 months. No factors, including IMDC or Khorana score, were identified to predict TE development. Seventy-two percent of TE resulted in hospitalization (9% TE-related mortality and 21% TE-related dose delay). TE (p < 0.0001), poor IMDC score (p < 0.0001), and Khorana score ≥ 2 (p < 0.0001) were associated with worse OS.
Patients with mRCC treated with IO had a high incidence of TE. TE was associated with risk of treatment delay, hospitalization, and mortality, while TE, IMDC poor risk, and Khorana score ≥ 2 were associated with worse survival. Further investigations into IO-associated TE are needed to identify benefit from primary thromboprophylaxis.
Patients with advanced renal cell carcinoma carry an increased risk of clotting, both in their arteries and veins. Historically, risk scores such as the Khorana score were used to assess which patients with solid tumors would benefit from preventative blood thinning medications as they undergo chemotherapy. Whether the Khorana score can be applied to use with immunotherapy is not known. Currently, limited knowledge exists of the impact of immunotherapy on additional clotting in patients with renal cell carcinoma. This study shows an increased incidence of clotting under immunotherapy treatment in patients with advanced renal cancer compared with rates seen in the literature. This study highlights an associated risk of hospitalization, need to stop cancer therapy, as well as risk of death from clotting. Additionally, we determine that clotting, poor disease pathology (as assessed by the International Metastatic Renal Cell Carcinoma Database Consortium), and a Khorana score of ≥2 are predictors of a worse overall survival. This information will be useful in future studies that will address the usefulness of preventative blood thinner medications in this high-risk population.
Targeted oncology. 2021 Nov 06 [Epub ahead of print]
Iris Y Sheng, Shilpa Gupta, Chandana A Reddy, Dana Angelini, Pauline Funchain, Tamara A Sussman, Joseph Sleiman, Moshe C Ornstein, Keith McCrae, Alok A Khorana
Department of Medicine, Beth Israel Lahey Mt. Auburn Hospital, Boston, MA, USA., Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, 10201 Carnegie Ave/CA 60, Cleveland, OH, 44106, USA., Department of Radiation Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA., Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA., Department of Gastroenterology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA., Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, 10201 Carnegie Ave/CA 60, Cleveland, OH, 44106, USA. .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/34741719