Extramedullary Disease-Achilles Heel in Myeloma?

Am J Hematol. 2026 Mar;101(3):521-536. doi: 10.1002/ajh.70138. Epub 2025 Dec 29.

Abstract

Despite advances in therapy, extramedullary disease (EMD) remains an aggressive form of multiple myeloma associated with poor outcomes. Patients with true EMD, in which plasmacytomas have become completely independent of bone, have a particularly poor prognosis. The pathogenesis of EMD is driven by complex mechanisms involving loss of adhesion molecules, heterogeneous genetic and epigenetic changes, and a solid tumor-like architecture within the microenvironment. Although the introduction of advanced imaging techniques and immunotherapy has led to improved detection and more promising outcomes and regimens, respectively, more prospective studies dedicated to true EMD are needed.

Keywords: bispecific antibodies; immunotherapy; paramedullary; relapsed myeloma.

Publication types

  • Review

MeSH terms

  • Humans
  • Multiple Myeloma* / genetics
  • Multiple Myeloma* / pathology
  • Multiple Myeloma* / therapy
  • Plasmacytoma* / genetics
  • Plasmacytoma* / pathology
  • Plasmacytoma* / therapy
  • Prognosis
  • Tumor Microenvironment