A retrospective population-based cohort study of patients with multiple myeloma receiving treatment with immunomodulatory agents was the basis for the development and validation of a new model to assess for risk of venous thromboembolism (VTE) in these patients. The findings from this study were published in the Journal of the National Comprehensive Cancer Network.1
Patients with multiple myeloma receiving immunomodulatory agents (eg, lenalidomide, thalidomide) are at increased risk of developing VTE. In 2008, based on consensus from the International Myeloma Working Group, a guide for assessing VTE risk in these patients was developed that incorporated multiple individual risk factors, and myeloma disease- and therapy-related risk factors.2
According to this tool, 2 or more VTE risk factors warrant full dose anticoagulation with low molecular weight heparin or warfarin, whereas once daily aspirin is recommended for those with 1 or no VTE risk factors. This risk assessment consensus guide was subsequently incorporated into the National Comprehensive Cancer Network (NCCN) Cancer-Associated Venous Thromboembolic Disease Guidelines3; although the tool has not been independently validated.
In this study, a new VTE risk assessment tool called SAVED was derived based on findings from a group of 2397 patients from the Surveillance Epidemiology and End Results (SEER)-Medicare database. Inclusion criteria included age 65 years or older, a new diagnosis of multiple myeloma between January 2007 and December 2013, and a prescription for an immunomodulatory agent within 1 year of disease diagnosis. Exclusion criteria included a diagnosis of VTE within 6 months of the initial prescription for an immunomodulatory agent. Patients with either 1 inpatient or 2 outpatient claims separated by at least 30 days coupled with a prescription for an anticoagulant within 90 days were considered to have experienced a VTE.
The SAVED VTE risk assessment tool involves only 5 variables weighted according to their association with VTE: Surgery within 90 days (+2 points); Asian race (-3 points); Venous thromboembolism history (+3 points); age older than 80 [Eighty] years (+1 point); Dexamethasone dose (standard dose, +1; high dose, +2). Using this model, VTE risk is high if cumulative points equal or exceed 2.
This new risk assessment tool was independently validated in an external cohort of 1251 patients included in the Veterans Health Administration database who were selected based on characteristics similar to those for patients in the SEER-Medicare group. In both the derivation and external validation patient cohorts, approximately 30% of patients were determined to be at high risk of VTE based on the SAVED tool.
A comparison of patient subgroups in the derivation dataset who were determined to be at low- and high-risk of VTE, according to the SAVED tool, showed that a high-risk designation was significantly associated with an increase in the incidence of VTE (hazard ratio [HR], 1.85; P <.01). Similar findings were observed in the external validation cohort (HR, 1.98; P <.01).
Conversely, a comparison of subgroups within these 2 cohorts with high- and low-VTE risk designations according to the risk assessment guide currently incorporated in the NCCN Guidelines showed that high-risk patients were not significantly more likely than low-risk patients to experience a VTE (derivation cohort: HR 1.21, P =.17; validation cohort: HR 1.41, P =.07).
“We are hopeful that this clinical tool will aid informed shared decision-making between providers and patients with multiple myeloma regarding VTE risk before immunomodulatory drug initiation. Future prospective studies are needed to define the best VTE prevention strategy for patients with multiple myeloma within a given risk stratum,” the study authors concluded.
1. Li A, Wu Q, Luo S, et al. Derivation and validation of a risk assessment model for immunomodulatory drug-associated thrombosis among patients with multiple myeloma. J Natl Compr Canc Netw. 2019;17(7):840-847.
2. Palumbo A, Rajkumar SV, Dimopoulos MA, et al; International Myeloma Working Group. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22(2):414-423.
3. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Cancer-Associated Venous Thromboembolic Disease. Version 1.2019 — February 28, 2019. https://www.nccn.org/professionals/physician_gls/pdf/vte.pdf. Accessed August 2, 2019.