Derivation and Validation of a Risk Assessment Model for Immunomodulatory Drug-Associated Thrombosis Among Patients With Multiple Myeloma

J Natl Compr Canc Netw. 2019 Jul 1;17(7):840-847. doi: 10.6004/jnccn.2018.7273.

Abstract

Background: Although venous thromboembolism (VTE) is a significant complication for patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs), no validated clinical model predicts VTE in this population. This study aimed to derive and validate a new risk assessment model (RAM) for IMiD-associated VTE.

Methods: Patients with newly diagnosed MM receiving IMiDs were selected from the SEER-Medicare database (n=2,397) to derive a RAM and then data from the Veterans Health Administration database (n=1,251) were used to externally validate the model. A multivariable cause-specific Cox regression model was used for model development.

Results: The final RAM, named the "SAVED" score, included 5 clinical variables: prior surgery, Asian race, VTE history, age ≥80 years, and dexamethasone dose. The model stratified approximately 30% of patients in both the derivation and the validation cohorts as high-risk. Hazard ratios (HRs) were 1.85 (P<.01) and 1.98 (P<.01) for high- versus low-risk groups in the derivation and validation cohorts, respectively. In contrast, the method of stratification recommended in the current NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease had HRs of 1.21 (P=.17) and 1.41 (P=.07) for the corresponding risk groups in the 2 datasets.

Conclusions: The SAVED score outperformed the current NCCN Guidelines in risk-stratification of patients with MM receiving IMiD therapy. This clinical model can help inform providers and patients of VTE risk before IMiD initiation and provides a simplified clinical backbone for further prognostic biomarker development in this population.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use*
  • Databases, Factual
  • Female
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use
  • Male
  • Medicare
  • Middle Aged
  • Multiple Myeloma / complications
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / epidemiology
  • Multiple Myeloma / pathology
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • United States / epidemiology
  • Venous Thromboembolism / chemically induced
  • Venous Thromboembolism / drug therapy*
  • Venous Thromboembolism / epidemiology
  • Venous Thromboembolism / pathology
  • Venous Thrombosis / chemically induced
  • Venous Thrombosis / drug therapy*
  • Venous Thrombosis / epidemiology
  • Venous Thrombosis / pathology

Substances

  • Anticoagulants
  • Immunologic Factors