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

Rajshekhar Chakraborty, Irbaz Bin Riaz, Saad Ullah Malik, Naimisha Marneni, Alex Mejia Garcia, Faiz Anwer, Alok A. Khorana, S. Vincent Rajkumar, Shaji Kumar, M. Hassan Murad, Zhen Wang, Safi U. Khan, Navneet S. Majhail

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2 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalCancer
DOIs
StateAccepted/In press - Jan 1 2020

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Keywords

  • lenalidomide
  • multiple myeloma
  • survivorship
  • thromboprophylaxis
  • venous thromboembolism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Chakraborty, R., Bin Riaz, I., Malik, S. U., Marneni, N., Mejia Garcia, A., Anwer, F., Khorana, A. A., Rajkumar, S. V., Kumar, S., Murad, M. H., Wang, Z., Khan, S. U., & Majhail, N. S. (Accepted/In press). Venous thromboembolism risk with contemporary lenalidomide-based regimens despite thromboprophylaxis in multiple myeloma: A systematic review and meta-analysis. Cancer. https://doi.org/10.1002/cncr.32682