• Extramedullary disease (EMD) in patients with MM is a sign of aggressive disease and is characterized by the ability of a clone and/or subclone to thrive and grow independent of the bone marrow microenvironment¹

There are different types of plasmacytomas in relation to the bone^1–3

• These different types of plasmacytomas impact OS and PFS for patients with MM²

• The prognosis for patients with MM and EMD (excluding bone involvement) is poor and considerably worse compared with patients with MM and no EMD, or with MM and paraskeletal plasmacytomas¹
• In a retrospective single-center study, a total of 518 patients with NDMM from January 2013 to December 2021 were enrolled, of which 121 presented with EMD at the initial diagnosis²
  • Patients were divided into three subgroups:²
    • Non-EMD (n=397)
    • Extramedullary-bone-related (EM-B; n=91)
    • Extramedullary-extraosseous (EM-E; n=30)
  • The EM-E group had the worst PFS and OS²

Figures reproduced from Wang J, et al. 2023, covered by a CC-BY-4.0 license: http://creativecommons.org/licenses/by/4.0/

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When defining EMD as only involving soft-tissue plasmacytomas unrelated to bone^1,4:

In patients with MM, risk of EMD is higher with⁵:

• Osteolytic lesions
• Hypercalcemia
• Exposure to more lines of therapy

Incidence of EMD is higher in patients with^5,6:

• High-risk cytogenetics
• High serum lactate dehydrogenase, indicative of highly proliferative disease

Incidence of EMD increases as⁵:

• Disease becomes more refractory

Location

While EMD can be found anywhere, in a study of 127 patients with MM and EMD relapse, the most common sites (≥10%) were^7†:

*The reported incidence of EMD varies considerably, and differences in diagnostic approach between studies are likely to contribute to this variability. ^†For genitourinary organs, spleen and gums (n=1, 0.8% each), pancreas (n=3, 2%), gastrointestinal tract and breast (n=10, 8% each). ^‡Always in addition to another site.

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Diagnosis

Treatment

• Patients with EMD have high unmet medical need; MM-focused therapies include chemotherapy, radiotherapy, stem cell transplant, immunomodulatory agents, proteasome inhibitors, and MM antigen-targeting immunotherapies such as CAR-T, monoclonal antibodies, and bispecific antibodies^1,2,11-13
• Treatment options for EMD with CNS involvement are limited. Systemic therapy, intrathecal therapy and cranial irradiation can be used, often in combination¹⁰
• Clinical trials dedicated to patients with EMD are exploring novel treatment regimens¹⁴

^§When available,¹⁸fluorodeoxyglucose (¹⁸F-FDG) PET/CT is recommended by the International Myeloma Working Group for the workup of patients with newly diagnosed and relapsed MM.¹⁵ Use of PET/CT and MRI provides the highest probability of EMD detection by combining the anatomical and functional imaging capability of PET/CT with the high resolution of soft tissues and CNS structures from MRI.¹⁶