Understanding Extramedullary Disease in Multiple Myeloma

Extramedullary disease (EMD) in multiple myeloma (MM) represents a complex and often aggressive form of the cancer that requires careful attention from oncology nurses and healthcare providers. Unlike typical myeloma, which primarily resides in the bone marrow, EMD involves myeloma cells forming tumors outside of this environment. This article provides a comprehensive overview of EMD, covering its definition, differentiation from related conditions, locations, risk factors, and implications for patient care.

Defining EMD Versus Paramedullary Disease

It’s crucial to distinguish between extramedullary disease (EMD) and paramedullary disease (PMD). EMD occurs when myeloma cells leave the bone marrow and establish independent tumors in soft tissues, organs, or the bloodstream. In contrast, PMD involves a direct extension of myeloma from the bone marrow into adjacent tissue spaces. Some researchers utilize the term bone-independent EMD (BI-EMD) to clarify discussions about EMD specifically [1].

EMD Locations

EMD can manifest in various locations throughout the body. Common presentations include:

• Solid Lesions: Extramedullary plasmacytoma
• Circulating Plasma Cells: Plasma cell leukemia
• Lymph Node Involvement: Often mimicking Hodgkin’s or non-Hodgkin’s lymphoma
• Other Sites: Skin, subcutaneous tissues, liver, spleen, and peritoneum (as intra-abdominal masses)

Patients may experience palpable masses (painful or painless), hepatomegaly, or splenomegaly. Rarely, EMD can affect the central nervous system (CNS-MM), presenting as aggressive meningeal infiltration or intraparenchymal plasmacytomas. CNS involvement necessitates treatment strategies capable of crossing the blood-brain barrier.

Timing and Occurrence of EMD

The incidence of EMD varies depending on the stage of the disease. It is uncommon in newly diagnosed patients, occurring in up to 5% of cases. However, it is more prevalent in patients with relapsed or refractory (R/R) disease, affecting up to 14% [1]. The location of EMD also tends to shift with disease progression; head and neck involvement is more common at diagnosis, while liver infiltration and pleural involvement are more frequently observed in R/R disease.

High-Risk Cytogenetics

Patients with EMD often exhibit high-risk cytogenetic abnormalities, including:

• del(13q) and del(17p)
• gain(1q21)
• t(4;14), t(14;16), and t(14;20)

Emerging research suggests a potential link between EMD and the mitogen-activated protein kinase (MAPK) pathway, specifically RAS–RAF mutations, based on whole-genome sequencing studies [1].

Real-World Data on EMD

A retrospective analysis conducted in London examined outcomes for adults with newly diagnosed MM. The study referred to EMD as BI-EMD and found it was present in 3.6% of patients at diagnosis and 2.4% at relapse. These findings differ from some other studies reporting higher incidence rates in R/R disease. The median follow-up period was 45 months. The study reinforced the understanding that EMD represents a distinct entity within MM, often requiring sensitive imaging and more intensive management [1].

Oncology Nursing Implications

Oncology nurses play a vital role in the diagnosis and management of EMD. Understanding the significance of CRAB criteria (hyperCalcemia, Renal insufficiency, Anemia, lytic Bone lesions/osteopenia) and biomarkers (such as M-protein or free light chain) is essential. EMD can coexist with CRAB features, or it can be present independently. Importantly, biomarker levels may not always correlate with the extent of EMD.

Early diagnosis is critical for optimizing patient outcomes. Nurses should be vigilant in assessing patients for new masses, enlarged lymph nodes, or other concerning symptoms. They should also identify patients at high risk for EMD at the time of relapse or recurrence and anticipate the potential need for aggressive therapies, such as chimeric antigen receptor (CAR) T cells or dual-target bispecific antibodies.

Patient Education

Resources like the video “What Is Extramedullary Disease in Myeloma” can be valuable tools for educating patients about their condition. By recognizing new assessment findings, understanding the disease biology and associated risk factors, and providing comprehensive patient education, oncology nurses can significantly improve the care of individuals with EMD.