Multiple myeloma, also called myeloma, is a type of cancer where plasma cells in bone marrow replicate out of control. Plasma cells are a type of white cell that help your body fight infection.

The National Cancer Institute estimates that in the United States, nearly 35,000 people were diagnosed with multiple myeloma in 2021.

The hallmark signs and symptoms of multiple myeloma fall under the acronym CRAB, which stands for:

  • Calcium elevation
  • Renal failure (kidney failure)
  • Anemia
  • Bone disease

Doctors use the presence of these symptoms to differentiate from precancerous disease and to guide treatment.

In this article, we take a deeper look at the CRAB symptoms of multiple myeloma, including why doctors use this acronym and how the presence of these symptoms influences your treatment.

Multiple myeloma develops in plasma cells in your bone marrow. Cancerous plasma cells crowd out healthy blood cells and produce M protein. A buildup of M protein can damage the kidneys.

In a 2017 study, researchers found that among 113 people with symptomatic myeloma treated at a hospital in Japan:

  • 68 percent had bone disease
  • 57 percent had anemia
  • 29 percent had kidney failure
  • 6 percent had calcium elevation

Calcium elevation

Multiple myeloma activates cells that break down bone called osteoclasts, which leads to elevated calcium in the blood, also called hypercalcemia. Elevated calcium may cause symptoms such as:

Renal (kidney) damage

The accumulation of M protein in the blood can result in kidney damage and kidney failure. Hypercalcemia can also impair kidney function.

The early stages of kidney disease often don’t cause symptoms, but your doctor might see signs of kidney problems in your urine and blood tests.

Early symptoms of kidney damage can include:

Anemia

Anemia is a low blood cell count. Overproduction of abnormal plasma cells can crowd out healthy red blood cells, white blood cells, and platelets, which help your blood clot after an injury.

Low levels of healthy blood cells can lead to:

Bone disease

Increased activation of osteoclasts causes the bones to break down. It often causes symptoms such as:

  • easy fractures
  • bone pain
  • back problems
  • bone weakness

If the spine becomes weak from loss of bone mass, there’s an increased risk of a spinal fracture. A spinal fracture can compress the spinal cord and cause:

  • sudden and severe back pain
  • numbness, usually in the legs
  • muscle weakness, usually in the legs

Proteins produced by cancerous plasma cells can damage the nerves and lead to:

  • muscle weakness
  • numbness
  • pins and needles

A large amount of M protein can thicken the blood. Reduced blood flow to the brain may cause:

  • confusion
  • dizziness
  • stroke-like symptoms, such as weakness on one side

Doctors use the presence of CRAB symptoms to diagnose myeloma and to guide treatment.

Multiple myeloma evolves from a precancerous condition called monoclonal gammopathy of undetermined significance (MGUS). This condition comes with about a 1 percent chance of progressing to multiple myeloma per year.

MGUS can also develop into another precancerous condition called smoldering multiple myeloma, which has about a 10 percent chance of turning into multiple myeloma per year.

Doctors use the CRAB symptoms to estimate how far the disease has progressed and to help differentiate multiple myeloma from its precancerous forms.

Doctors can use the CRAB symptoms to differentiate between active multiple myeloma and MGUS.

MGUS needs to be actively monitored with regular blood tests but doesn’t require treatment. Your doctor may recommend taking medications to increase your bone density.

Multiple myeloma is diagnosed if at least one CRAB symptom or one of the following three specific biomarkers develops:

  • the clonal bone marrow plasma cells are greater than 60 percent
  • the serum free light chain (FLC) ratio is greater than 100 mg/L (the involved FLC level must also be greater than 100 mg/L)
  • more than one focal lesion on an MRI scan

Many people with myeloma show abnormalities in lab blood tests before they develop symptoms.

Multiple myeloma requires active treatment if one or more CRAB symptom develops. Treatment usually consists of medications to destroy cancer cells and treat specific symptoms. People in otherwise good health may also be candidates for bone transplants.

In the United States, the most common initial therapy for people eligible for bone transplants is a combination of the medications:

A long-term, follow-up study of people who received initial treatment with Velcade, Revlimid, and dexamethasone followed by transplant and maintenance therapy found that half of them lived longer than 10.5 years.

The development of certain CRAB symptoms may be associated with a poorer outlook.

Hypercalcemia and anemia can be serious but are largely reversible without long-term complications.

In a 2017 study, researchers examined the impact of CRAB symptoms on the survival of people with myeloma receiving new types of medications.

They found that people with hypercalcemia and bone disease had a significantly worse outlook than people without these symptoms. The development of anemia or kidney failure wasn’t associated with a poorer survival time.

Researchers concluded that the development of bone disease may be the strongest factor for people’s outlook since it may indicate the disease is close to an advanced stage.

The most common signs and symptoms of multiple myeloma are abbreviated with the acronym CRAB. The development of these symptoms helps differentiate myeloma from precancerous diseases.

Active treatment is needed if CRAB symptoms develop. Treatment usually involves taking medications to destroy myeloma cells and to treat the specific symptoms it causes.

Your doctor can help you develop a treatment plan tailored to your needs. They can also help you find clinical trials you may be eligible for.