Application of risk factors for venous thromboembolism in patients with multiple myeloma starting chemotherapy, a real‐world evaluation

Abstract

IntroductionWithin the first year of diagnosis, up to 1 in 3 multiple myeloma (MM) patients will experience a venous thromboembolism (VTE). The International Myeloma Working Group (IMWG) has thromboprophylaxis guidelines that stratify patients into low or high risk for thrombosis and subsequently recommend thromboprophylaxis, but it is unknown if these recommendations are being followed or if they are effective. The purpose of this study was to assess efficacy of the IMWG guidelines and investigate other potential VTE risk factors.MethodsStudy participants were treated at the University of Kansas Medical Center between 2007 and 2013, and charts were reviewed to extract data. Cases (MM and VTE) were matched to controls (MM and no VTE) at approximately 1:3 ratio based on gender, age (±5 years), and time of MM diagnosis (±5 years).ResultsA total of 80 cases and 211 controls were matched. Most patients (82%) were considered high risk for experiencing a VTE at the time of their MM diagnosis and 18% were considered low risk. Neither risk category (P = 0.16) nor thromboprophylaxis at baseline (P = 0.37) predicted VTE, though cases were more likely than controls to have an increased risk of thrombosis at the time of clot compared to their baseline risk (P = 0.09).ConclusionOur results suggest that IMWG guidelines are not being consistently followed and therefore could not be validated. Additional risk factors were not identified, but risk for VTE may change over time suggesting patients may require ongoing assessment of VTE risk and thromboprophylaxis throughout the disease course.

Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools

“…There was no association between the initial risk stratification and the mode of thromboprophylaxis of use. Therefore, it was demonstrated that guideline concordance in terms of either aspirin (ASA) or LMWH was lower than expected [22].…”

“…Body mass index >25, Age >75, Personal or family history of VTE, Central venous catheter, Acute infection or Hospitalization, Blood clotting disorders or Thrombophilia, Immobility with performance status of >1, Comorbidities (liver, renal impairment, chronic obstructive pulmonary disorder, diabetes mellitus, chronic inflammatory bowel disease), Race (Caucasian is a risk factor) These guidelines have been available since 2014; however, data from clinical trials demonstrate that the rates of residual VTE remain high [22][23][24]. Therefore, it is safe to conclude that the current risk stratification is suboptimal and fails to fully capture and distinguish between low, intermediate, and high-risk MM patients for VTE.…”

“…In addition, the extent to which the available algorithm is being applied in every day clinical practice is questionable. There is also a lack of formal recommendations for patients on non-IMiD-containing regimens [13,22,24]. There is the need for optimization of the current tool utilizing a risk assessment model (RAM) that combines disease-specific, patient-specific, and treatment specific risk factors to accurately stratify VTE risk and guide thromboprophylaxis.…”

Optimizing Thromboembolism Prophylaxis for the Contemporary Age of Multiple Myeloma

“…Unfortunately, both the accuracy of the IMWG/NCCN model for predicting the development of VTE, as well as its use outside of clinical trials, have been poor. 18,19 Furthermore, recent attempts at validating the IMWG/NCCN model in 2 large cohorts-SEER-Medicare and Veterans Administration Healthcare System-demonstrated that the model's discriminatory performance as measured by Harrell's c-statistic (measured from 0.5-1.0 as the best "fit" of a propensity score model assessing the risk) was suboptimal in both groups, at 0.52 and 0.55, respectively. 16,17 On the other hand, both the SAVED and the IMPEDE VTE models performed slightly better, with external validations at 0.60 and 0.64, respectively.…”

“…A real-world study of VTE prophylaxis in NDMM demonstrated that only 19% of patients received appropriate prophylaxis per the IMWG guidelines. 18 A recent analysis of the GRIFFIN trial similarly showed that only 60% of patients treated with DRVd and 67% of those treated with RVd were receiving antithrombotic prophylaxis at the time of their VTE (ASA in 40% and 60% of patients, and LMWH in 10% and 7% of patients, respectively), suggesting that use of antithrombotic prophylaxis remains suboptimal even among mostly academic centers. 30 Finally, prospective validation of the SAVED and IMPEDE-VTE models is needed in order to determine the ideal thromboprophylaxis strategy based on baseline risk stratification and treatment regimen, ideally also incorporating biomarkers predictive of VTE risk.…”