Multiple myeloma is a cancer of plasma cells in the bone marrow. Plasma cells produce antibodies (immunoglobulins). When myeloma develops, abnormal plasma cells multiply and produce abnormal antibodies, damaging bones and affecting kidney function. Modern treatments have dramatically improved outcomes and quality of life.

What Is Multiple Myeloma?

Multiple myeloma originates in the bone marrow. Cancerous plasma cells accumulate, crowding out healthy cells and producing excess abnormal immunoglobulin (M-protein). This causes bone destruction, anemia, kidney damage, and infections.

Key fact: Myeloma can be preceded by precursor conditions (MGUS, smoldering myeloma) and monitored with blood tests (M-protein levels, free light chains) before active disease requires treatment.

Risk Factors

  • Age: Median age at diagnosis is 70 years old.
  • Male sex: Men have higher incidence than women.
  • Race/ethnicity: African Americans have 2x higher incidence and often worse outcomes.
  • Family history: Familial clustering increases risk.
  • Obesity and occupational exposures: Possible risk factors under investigation.

Symptoms & Complications

CRAB criteria define symptomatic myeloma:

  • C: Calcium elevation (bone disease)
  • R: Renal insufficiency (kidney damage)
  • A: Anemia (low hemoglobin)
  • B: Bone lesions (on imaging)

Other symptoms:

  • Bone pain (especially back, ribs)
  • Fractures (weakened bones)
  • Fatigue and weakness
  • Recurrent infections
  • Kidney dysfunction
  • Hyperviscosity (thick blood causing confusion, bleeding)

Diagnosis

Diagnostic workup:

  • Blood tests: CBC (hemoglobin, platelets), chemistry panel (calcium, creatinine), LDH, albumin, beta-2 microglobulin.
  • M-protein detection: Serum protein electrophoresis, immunofixation, quantitative immunoglobulin levels.
  • Free light chains: Prognostic marker; high ratio predicts aggressive disease.
  • Bone marrow biopsy: Confirms clonal plasma cells (≥10% diagnostic).
  • Imaging: Skeletal survey, MRI, or PET scan to assess bone disease.
  • Molecular testing: Cytogenetic abnormalities (t(4;14), del17p) and FISH studies guide risk stratification.

Staging & Risk Stratification

Revised International Staging System (R-ISS) incorporates:

  • Serum beta-2 microglobulin
  • Albumin level
  • Cytogenetic abnormalities

Risk categories guide treatment intensity and prognosis.

Treatment Options

Watch-and-Wait (Smoldering/MGUS)

For precursor states or early asymptomatic disease, close monitoring with blood/imaging without immediate treatment.

Proteasome Inhibitors

Bortezomib (Velcade), carfilzomib (Kyprolis), ixazomib (Ninlaro). Reversibly inhibit proteasome degradation of proteins, triggering cancer cell death. Often first-line.

Immunomodulatory Agents (IMiDs)

Lenalidomide (Revlimid), pomalidomide (Pomalyst). Enhance immune killing of myeloma cells and have anti-angiogenic effects.

Monoclonal Antibodies

Daratumumab (Darzalex), elotuzumab (Empliciti). Target myeloma cell surface antigens (CD38, SLAMF7) and enhance immune recognition.

Stem Cell Transplantation (SCT)

High-dose chemotherapy followed by reinfusion of patient's own stem cells. Often used in younger/fit patients as consolidation after induction therapy. Improves complete response rates and progression-free survival.

CAR-T Cell Therapy

Emerging option for relapsed/refractory myeloma. Idecabtagene vicleucel (Abecma) is FDA-approved. Engineered T cells attack myeloma cells expressing BCMA.

Bi-specific Antibodies

Newer agents that bridge myeloma cells to immune cells for destruction.

Side Effects & Management

From proteasome inhibitors: Peripheral neuropathy (nerve damage), diarrhea, fatigue, low blood counts.

From IMiDs: Blood clots (require anticoagulation), low blood counts, fatigue, neuropathy.

From monoclonal antibodies: Infusion reactions, infections (enhanced immunotherapy can be a double-edged sword), tumor flare.

From SCT: Severe infections, bleeding, organ toxicity, secondary malignancies (rare).

Supportive care essential: Anticoagulation, antimicrobial prophylaxis, bone-directed therapy (bisphosphonates or RANKL inhibitors for bone disease and pain), pain management.

Prognosis & Outcomes

Multiple myeloma was incurable, but modern therapies have transformed outcomes:

  • Median overall survival: 5-10 years with current treatments (improvement from 3 years a decade ago).
  • Standard-risk: Often 10+ years with multiagent therapy.
  • High-risk: Shorter median survival but still achievable remissions with aggressive treatment.

Most patients will eventually relapse, but newer therapies provide multiple lines of treatment options.

Seek Immediate Care If You Experience:

  • Severe bone pain uncontrolled by medication
  • Signs of spinal cord compression (numbness/weakness in legs)
  • Severe kidney dysfunction or oliguria (low urine output)
  • Hyperviscosity symptoms (confusion, severe headache, visual changes)

Key Questions for Your Doctor

  • What is my disease stage and risk category?
  • Do I need treatment now, or should I watch and wait?
  • Am I a candidate for stem cell transplantation?
  • What is the planned treatment regimen and expected response?
  • What side effects should I monitor for?
  • How often will we monitor my M-protein and kidney function?
  • Are there new therapies or clinical trials available for my disease?