Multiple Myeloma

What it is

Overview

Multiple myeloma is a cancer of plasma cells — the immune cells that produce antibodies. Abnormal plasma cells (myeloma cells) accumulate in the bone marrow, crowding out healthy blood cells and producing a non-functional antibody protein called M-protein. Myeloma causes bone destruction, kidney damage, anemia, and immune deficiency. While not curable in most cases, treatment has dramatically improved over the past decade.

Biology

How It Develops

Myeloma evolves from a precursor condition called monoclonal gammopathy of undetermined significance (MGUS). Over years, plasma cells acquire additional mutations in the RAS/MAPK pathway, MYC translocations, and chromosomal abnormalities (trisomies, IGH translocations). The bone marrow microenvironment plays a key role in supporting myeloma cell survival, making it a target for therapy.

Warning signs

Symptoms

• —Bone pain, especially in the back, hips, and skull
• —Fractures with little or no trauma (pathologic fractures)
• —Fatigue and weakness (anemia)
• —Frequent infections
• —Kidney problems (from light chain deposition)
• —High blood calcium (hypercalcemia): nausea, confusion, thirst

Detection

Diagnosis Methods

• —Serum protein electrophoresis (SPEP) and immunofixation
• —Serum free light chains
• —Bone marrow biopsy with flow cytometry
• —Whole-body low-dose CT or PET
• —MRI of spine
• —Complete blood count and comprehensive metabolic panel

Medical care

Treatment Options

• —Proteasome inhibitors (bortezomib, carfilzomib, ixazomib)
• —Immunomodulatory drugs (lenalidomide, pomalidomide)
• —Monoclonal antibodies (daratumumab, isatuximab)
• —Autologous stem cell transplant
• —CAR-T cell therapy (ide-cel, cilta-cel)
• —Bispecific antibodies (teclistamab, elranatamab)

Data

Statistics

Prevention

Risk Factors

• —Age over 65
• —African American heritage (2x higher risk)
• —Male sex
• —Prior monoclonal gammopathy (MGUS or smoldering myeloma)
• —Obesity

Further reading

Resources