Multiple Myeloma and Anemia: The Critical Connection

Reading Time: 3 mins 

Libby-Ann Harpaul-Sahadeo 

What is Multiple Myeloma? 

Multiple myeloma (MM) is a blood cancer that may sometimes present as tumors called plasmacytomas, which are clusters of these malignant plasma cells. In this disease, healthy plasma cells turn cancerous and multiply uncontrollably. The cancerous plasma cells also produce excessive amounts of an abnormal antibody, M protein, a key indicator of the disease. This overgrowth displaces normal infection-fighting cells. 

Individuals with multiple myeloma (MM) often experience various symptoms, commonly referred to as CRAB: hypercalcemia, renal dysfunction, anemia, and bone pain. These symptoms are used as clinical indicators for diagnosing MM. Interestingly, anemia-related fatigue and bone-related pain symptoms originate in the bone marrow, where the disease damages its structure and reduces the production of red blood cells.  This leads to low hemoglobin levels, exacerbating oxygen deprivation in the body, which can result in symptoms of anemia, such as weakness, shortness of breath, and an increased perception of bone pain.  MM often presents as Anemia, making it its most common symptom. Let’s explore this primary symptom of MM, including its characteristics, warning signs, and treatment options.

What is Anemia?

Multiple myeloma causes anemia because cancerous plasma cells crowd out healthy blood-forming cells in the bone marrow, reducing the space for red blood cell production. It can also lead to anemia through kidney damage caused by the disease, which decreases erythropoietin production—the hormone that stimulates the creation of red blood cells—and sometimes as a side effect of treatments.

The figure above illustrates two panels for comparison. Panel (A) depicts healthy bone marrow, where various blood cells mature normally, alongside bone marrow affected by MM, which shows the proliferation and accumulation of abnormal plasma cells (myeloma cells). Panel (B) highlights the systemic effects of these malignant cells, specifically focusing on bone lesions and impaired hematopoiesis (the production of red blood cells), which can lead to anemia. These features are key clinical characteristics of the disease.

A study found that 73% of over a thousand patients were diagnosed with anemia (hemoglobin levels below 12 g/dL). Initially, at least two-thirds of these patients had anemia, and nearly all of them developed anemia as the disease progressed.

• Between 60% and 75% of patients present with anemia when initially diagnosed with MM.

• Throughout disease progression, over 90–95% of myeloma patients experience anemia at some point.
• Anemia is seen in more than two-thirds of all cases and frequently results from bone marrow infiltration, erythropoietin deficiency, and chronic inflammation.
• Demographic Disparities: Epidemiological data show a significantly higher incidence rate, almost double in Black populations compared to White populations, and a slight male predominance. This disparity is primarily attributed to differences in tumor biology and genetic factors.

The malignancy also causes severe bone damage—myeloma cells promote osteoclast activity through the increased expression of RANKL (Receptor Activator of NF-κB Ligand) and other factors, while hindering new bone formation by suppressing osteoblast function via the secretion of DKK1 (Dickkopf-1), resulting in lytic lesions and pathological fractures.

Some malignancies, such as MM, involve the rapid proliferation of abnormal plasma cells in the bone marrow, which displaces normal hematopoietic stem cells, consequently inhibiting the production of healthy blood cells, including red blood cells. The link between MM and anemia is due to this suppression, which reduces the number of red blood cells available to supply oxygen to the body’s tissues.

The prevalence of anemia acts as a critical, unifying early warning sign, intrinsically linked to both the malignant infiltration and the skeletal destruction characteristic of MM. 

The Warning signs

Drowsiness and fatigue, while common in busy lives, are significant indicators of underlying issues like how the low red blood cell count (anemia) that is often the most common presenting symptom of MM. However, these are not the only warning signs. Other symptoms include:

• Numbness or tingling in your arms or legs
• Nausea and vomiting
• Unexplained weight loss 
• Exhaustion
• Confusion
• Thirst
• Bone pain in the chest, spine, or hips

Early detection is important for treating MM; recognizing warning signs and consulting a provider can lead to early intervention.

How to Treat Anemia and Manage Symptoms with Myeloma

Treating anemia associated with MM enables the bone marrow to regain its normal capacity for producing red blood cells (RBCs). For direct management, options can include transfusions for immediate relief of severe symptoms, such as fatigue, or the use of Erythropoiesis-Stimulating Agents (ESAs), which encourage the bone marrow to produce RBCs over time. These are often supplemented with iron or B12/folate if deficiencies exist. Ultimately, the choice between these direct treatments is customized based on the severity of the anemia, its cause (whether due to disease or treatment), and the overall goal of maintaining a good quality of life by reducing debilitating fatigue.

Header Image Source: https://www.hopkinsmedicine.org/health/conditions-and-diseases/myeloma-bone-disease-multiple-myeloma

Edited by Joycelyn Ghansah

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