Multiple Myeloma (MM)

Multiple myeloma (MM) is a blood cancer that starts in plasma cells, a type of white blood cell found in the bone marrow.

Plasma cells normally produce antibodies that help fight infections. In multiple myeloma, abnormal plasma cells multiply uncontrollably and produce large amounts of an abnormal antibody called a monoclonal protein (M protein).

As these cells build up, they can interfere with normal blood cell production and damage different organs, leading to:

• Bone damage and bone pain

• Anemia and an increased risk of infection

• Kidney problems

• High blood calcium levels

Multiple myeloma is generally considered a chronic, treatable disease that often requires long-term management. New treatments—including targeted therapy, immunotherapy, autologous stem cell transplantation, and CAR-T cell therapy—have significantly improved outcomes for many patients.

The exact cause of multiple myeloma is unknown, but several factors are associated with an increased risk.

These include:

• Older age: Most patients are diagnosed after age 65.

• Male sex: Men are affected slightly more often than women.

• Monoclonal gammopathy of undetermined significance (MGUS): MGUS is a precursor condition that can progress to myeloma in a small percentage of patients each year.

• Family history: Having a close relative with multiple myeloma slightly increases risk.

• Obesity and certain environmental exposures: These may contribute to risk in some people.

Most people with MGUS never develop myeloma, and many patients with multiple myeloma have no identifiable risk factors.

Some people have no symptoms when myeloma is first detected through abnormal blood tests or an M protein found during routine evaluation.

Common symptoms of active myeloma include:

Bone symptoms

• Persistent bone pain, especially in the back, ribs, or pelvis

• Bone destruction or fractures

• Compression fractures of the spine

Symptoms related to anemia

• Fatigue

• Weakness

• Shortness of breath

• Pale skin

Infections

• Recurrent infections

• Fever

• More frequent respiratory or urinary tract infections

Kidney and calcium-related symptoms

• Increased thirst and urination

• Nausea or constipation

• Loss of appetite

• Confusion or drowsiness in severe hypercalcemia

Diagnosing multiple myeloma usually requires a combination of blood, urine, bone marrow, and imaging tests.

Blood tests

These may include:

• Complete blood count (CBC)

• Kidney function and calcium levels

• Serum protein electrophoresis (SPEP)

• Immunofixation electrophoresis (IFE)

• Serum free light chain assay

These tests help identify and measure M protein and assess disease activity.

Urine tests

A 24-hour urine collection and urine immunofixation can detect monoclonal light chains (Bence Jones proteins) and help evaluate kidney involvement.

Bone marrow tests

Bone marrow aspiration and biopsy confirm the percentage of plasma cells and may include:

• Flow cytometry

• FISH testing

• Molecular genetic testing

These findings help determine disease risk and guide treatment.

Imaging

Common imaging studies include:

• Whole-body low-dose CT

• PET/CT

• MRI

These tests identify bone lesions, bone marrow involvement, and fracture risk.

Treatment for multiple myeloma is individualized based on age, overall health, disease risk, and whether stem cell transplantation is appropriate.

Treatment often includes induction therapy, autologous stem cell transplantation for eligible patients, consolidation therapy, maintenance therapy, and treatment for relapse if needed.

• Watchful Waiting: People with MGUS or most cases of smoldering multiple myeloma are monitored rather than treated immediately.Monitoring typically includes blood tests, urine tests, M protein measurements, and imaging when needed.

  
  

• Drug Therapy: Modern myeloma treatment usually combines several types of medications.

  
  

• Targeted therapy: Proteasome inhibitors and other targeted drugs interfere with myeloma cell survival.

  
  

• Immunomodulatory drugs: These medications help the immune system fight myeloma while also slowing tumor growth.

  
  

• Monoclonal antibody therapy: Monoclonal antibodies recognize specific proteins on myeloma cells and help the immune system destroy them.

  
  

• Chemotherapy: Chemotherapy is still used in combination regimens and as high-dose treatment before autologous stem cell transplantation.

  
  

• Radiation Therapy: Radiation therapy is mainly used for localized disease, including painful bone lesions, areas at risk of fracture, or tumor compression.

  
  

• Autologous Stem Cell Transplantation: Autologous hematopoietic stem cell transplantation remains an important standard treatment for eligible patients. The typical process includes: induction therapy, collection of the patient's own stem cells, high-dose chemotherapy, stem cell infusion to restore bone marrow function. While transplantation is not usually curative, it can prolong remission.

  
  

• CAR-T Cell Therapy: CAR-T cell therapy has become an important option for selected patients with relapsed or refractory multiple myeloma. The treatment involves collecting T cells, genetically engineering them to recognize myeloma cells, and infusing them back into the patient.

  
  

• Bispecific Antibody Therapy: Bispecific antibodies are newer immunotherapies that connect T cells with myeloma cells to help the immune system destroy cancer cells. These therapies are primarily used for selected patients with relapsed or refractory disease.

  
  

• Maintenance Therapy: Maintenance therapy may help prolong remission and reduce the risk of relapse after an initial response to treatment. The choice of maintenance therapy depends on disease risk and treatment response.

  
  

• Clinical Trials: Clinical trials continue to evaluate new targeted therapies, immunotherapies, CAR-T cell therapies, bispecific antibodies, and combination treatment strategies for newly diagnosed, high-risk, relapsed, and refractory multiple myeloma.