Symptoms of Triple-Refractory Multiple Myeloma

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Triple refractory multiple myeloma is a condition marked by malignant transformation of plasma cells that can lead to multi-organ failure.

Triple-refractory multiple myeloma cases are often more advanced because they are resistant to treatment.

Early symptoms include nonspecific symptoms such as fatigue, weakness, and unexplained weight loss. Advanced symptoms include renal failure, bone pain and fractures, abnormal bleeding, and frequent infections.   

This article discusses the symptoms of triple-refractory multiple myeloma.

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Frequent Symptoms 

Multiple myeloma may present with generalized symptoms like fatigue, weakness, and unexplained weight loss. However, in general, symptoms that you experience will depend on the organ system that is affected.

Below, each affected organ system and corresponding symptoms are outlined.


Early on there may be no symptoms of renal (kidney) failure, but over time abnormal plasma cells and their proteins can combine with Tamm-Horsfall protein, forming large casts that are too big to pass through the glomeruli—the filtration unit of the kidney.

This blockage can damage the kidney over time, a condition known as cast nephropathy or myeloma kidney (kidney damage). These casts can also cause an inflammatory reaction in the tissues of the kidney. Over time your kidneys may lose their ability to get rid of excess salt, fluid, and body waste products leading to:

  • Weakness
  • Shortness of breath
  • Itching
  • Leg swelling


If cancerous cells build up in the bone marrow, they can lead to pain and fractures. They can also deplete other healthy blood cells such as platelets and red and white blood cells, increasing your risk of anemia (lack of healthy red blood cells), abnormal bleeding (low platelet count), and infections (low white blood cell count). 

Destruction of bone may also lead to a release of calcium into the bloodstream (hypercalcemia). Symptoms of hypercalcemia include:

  • Excess thirst (polydipsia)
  • Excess urination (polyuria)
  • Dehydration
  • Kidney failure
  • Severe constipation
  • Abdominal (belly) pain
  • Loss of appetite
  • Weakness
  • Feeling drowsy
  • Confusion

Nervous System

Malignant cells in multiple myeloma are toxic to nerve cells. Damaged nerve cells may cause numbness and tingling in your hands and feet, a loss of sensation, and the feeling of pins and needles throughout the body. 

Hyperviscosity—commonly observed in Waldenstrom macroglobulinemia—is a condition that occurs when your blood becomes so thick that your body's blood flow decreases. It is most commonly characterized by neurological changes such as: 

  • Seizure
  • Headache
  • Vertigo or stroke
  • Vision changes
  • Mucosal bleeding (blood in mucous)

Rare Symptoms 

If you have triple-refractory multiple myeloma you are more likely to experience more advanced symptoms such as: 

  • Unusual fractures
  • Bone pain
  • Frequent infections
  • Depression
  • Kidney failure
  • Bone marrow failure

Subgroup Indications

Multiple myeloma is a rare, incurable cancer that is more common in the following groups:

  • Family history: Having a family history of multiple myeloma, especially in a first-degree relative such as a parent, sibling, or child, increases your risk by 4 times. Treatment response may differ for each affected family member.
  • Black Americans: Black Americans are twice as likely as White Americans to develop myeloma.
  • Older people: Those who are 65 years and older are more likely to get multiple myeloma.
  • Men: Studies show that men are slightly more likely to get multiple myeloma than women. 

When to See a Healthcare Professional

If you are in your 50s or 60s and experience any of the aforementioned symptoms, you may want to contact a healthcare professional. Multiple myeloma is rare, so it is likely that your symptoms are the result of some other condition, but early diagnosis and treatment of multiple myeloma is associated with more favorable survival outcomes and quality of life.


Triple-refractory multiple myeloma can lead to multi-organ failure. This cancer is resistant to treatment. Early symptoms include nonspecific symptoms such as fatigue, weakness, and unexplained weight loss. Advanced symptoms include renal failure, bone pain and fractures, abnormal bleeding, and frequent infections.  

A Word From Verywell

Multiple myeloma affects multiple organs and systems throughout the body. If you are experiencing symptoms, your healthcare provider may refer you to a number of specialists—such as a nephrologist, neurologist, and physical therapist—that can help treat your symptoms. 

It’s important to note that multiple myeloma may initially present with no symptoms, underscoring the importance of frequent checkups with a healthcare provider. Healthcare professionals often take blood tests to help them diagnose multiple myeloma well before you experience symptoms.

8 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Shamard Charles, MD, MPH
Shamard Charles, MD, MPH is a public health physician and journalist. He has held positions with major news networks like NBC reporting on health policy, public health initiatives, diversity in medicine, and new developments in health care research and medical treatments.