Predicting Venous Thromboembolism in Patients With Non-Hodgkin Lymphoma

Author’s Perspective

Study author Roberto Mario Santi, MD: “Patients with non-Hodgkin lymphoma (NHL) have a high risk of venous thromboembolism (VTE) during the first six months of chemotherapy, comparable to that observed in patients with solid tumors. Our study shows that a high Khorana score and a histotype of diffuse large B-cell lymphoma (DLBCL) are associated with a higher risk [of VTE]. … Our results would not recommend a broad use of a primary prophylaxis against VTE with low-molecular-weight heparin for all patients with NHL undergoing active immune-chemotherapy. However, Khorana score and histotype DLBCL clearly identify a high-risk population.”

Venous thromboembolism (VTE) is a common complication associated with treatment for non-Hodgkin lymphoma (NHL), and VTE incidence is even higher among patients with diffuse large B-cell lymphoma (DLBCL), according to a pooled analysis of 12 phase II and III prospective trials that was published in Thrombosis and Haemostasis.

The authors, led by Roberto Mario Santi, MD, from the Division of Hematology, A. O. SS. Antonio e Biagio e Cesare Arrigo of Alessandria in Italy, also confirmed the clinical utility of the Khorana score (a VTE predictive tool that assigns risk based on lymphoma subtype, body mass index, platelet count, white blood cell count, and hemoglobin value).

Each of the 12 trials included patients with B-cell NHL who were actively enrolled between January 2005 and December 2014, for a total of 1,717 patients (median age = 57 years; range = 49-66 years). Patients had the following diagnoses: follicular lymphoma (FL) (41.5%), DLBCL (34.1%), mantle cell lymphoma (18.2%), and indolent non-FL (6.2%).

Researchers identified a total of 53 VTE episodes in 46 patients; 15 were superficial VTEs, and one involved an unusual site (portal vein thrombosis). Fifteen patients experienced 20 severe, grade 3/4 VTEs. The median time from study enrollment to VTE was 56 days (range = 30-84 days), and no fatalities related to VTE were reported.

The six-month cumulative incidence of any-grade VTE was 2.9 percent (95% CI 2.1-3.8), whereas the cumulative incidence for grade ≥3 VTE was 1.1 percent (95% CI 0.6-1.6).

Compared with other NHL subtypes, DLBCL was associated with an increased risk of any-grade VTE (hazard ratio [HR]=3.42; 95% CI 1.32-8.84; p=0.011). The researchers also observed a higher VTE risk among patients treated with lenalidomide, although the association was not statistically significant.

The following patient characteristics also appeared to be associated with developing VTE: age >65 years (HR for any-grade VTE = 2.66; 95% CI 1.08-6.56; p=0.034) and female sex (HR for ≥3 VTE = 4.60; 95% CI 1.39-15.17; p=0.012).

To test the predictive ability of the Khorana scoring system, researchers retrospectively calculated the VTE risk for 69.2 percent of evaluable patients (n=1,189):

  • low risk (score = 0): 0%
  • intermediate risk (score = 1-2): 88%
  • high risk (score = ≥3): 12%

Khorana score appeared to be positively associated with risk of VTE, the authors reported. The cumulative incidence of grade ≥3 VTE was 0.7 percent (95% CI 0.1-1.4) for those in the low-risk group, compared with 2.0 percent for those with a score ≥2 (p=0.048).

“The Khorana score and histotype clearly identify a high-risk population that should be prospectively evaluated for the relative risks and benefits of primary prophylaxis with low-molecular-weight heparin,” the authors concluded.

The study is limited by the heterogenous cohort of studies, which had different criteria, treatment regimens, and overall research designs.

The authors report no conflicts of interest.

Source: Santi RM, Ceccarelli M, Bernocco E, et al. A Khorana score and histotype predicts incidence of early venous thromboembolism in non-Hodgkin lymphomas: a pooled-data analysis of 12 clinical trials of Fondazione Italiana Linfomi (FIL). Thromb Haemost. 2017 April 27. [Epub ahead of print]