Venous thromboembolism risk with contemporary lenalidomide-based regimens despite thromboprophylaxis in multiple myeloma: A systematic review and meta-analysis

Cancer. 2020 Apr 15;126(8):1640-1650. doi: 10.1002/cncr.32682. Epub 2020 Jan 8.


Background: Thromboprophylaxis is routinely used with lenalidomide-based regimens in multiple myeloma because of a substantial risk of venous thromboembolism (VTE). However, little is known about the incidence of VTE with contemporary lenalidomide-based regimens. The objective of the current study was to estimate the incidence of VTE despite thromboprophylaxis with currently used lenalidomide-based regimens in patients with myeloma.

Methods: The Ovid MEDLINE, Embase, and Cochrane databases were queried from study inception to January 2019 for keywords to cover the following concepts: "lenalidomide," "venous thromboembolism," and "multiple myeloma." Phase 1, 2, and 3 clinical trials evaluating lenalidomide-based regimens with thromboprophylaxis were included. The pooled incidence rate of VTE was estimated using a random-effects model.

Results: The search generated 1372 citations, with 51 clinical trials and 9069 patients included for analysis. The most common thromboprophylaxis agents were aspirin, low-molecular-weight heparin or warfarin, administered either per risk-stratification or at investigators' discretion. The pooled incidence of VTE in trials of patients who had newly diagnosed and relapsed/refractory myeloma was 6.2% (95% CI, 5.4%-7.1%) over median treatment durations ranging from 2 to 34 cycles, which translated into 1.2 VTE events per 100 patient-cycles (95% CI, 0.9-1.7 VTE events per 100 patient-cycles). Among contemporary regimens, the risk of VTE was low with combined lenalidomide and low-dose dexamethasone (0.2 [95% CI, 0.1-0.6] events/100 patient-cycles) and lenalidomide maintenance (0.0 [95% CI, 0.0-0.7] events per 100 patient-cycles). VTE risk was higher with combined lenalidomide and low-dose dexamethasone plus proteasome inhibitors (1.3 [95% CI, 0.7-2.3] events per 100 patient-cycles).

Conclusions: Despite adequate thromboprophylaxis, lenalidomide-based regimens have a substantial risk of VTE in controlled clinical trial settings. Further studies are needed on new thromboprophylaxis strategies with regimens that have a high VTE risk.

Keywords: lenalidomide; multiple myeloma; survivorship; thromboprophylaxis; venous thromboembolism.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Systematic Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects*
  • Angiogenesis Inhibitors / therapeutic use*
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use
  • Dexamethasone / adverse effects
  • Dexamethasone / therapeutic use
  • Humans
  • Incidence
  • Lenalidomide / adverse effects*
  • Lenalidomide / therapeutic use*
  • Multiple Myeloma / drug therapy*
  • Venous Thromboembolism / chemically induced*


  • Angiogenesis Inhibitors
  • Anticoagulants
  • Dexamethasone
  • Lenalidomide