Multiple myeloma accounts for approximately 1% of all cancers and about 10% of hematologic malignancies. It most commonly affects individuals over the age of 65, with a median age at diagnosis around 70. Men are affected slightly more often than women, and incidence is about twice as high in African Americans compared to Caucasians.

The exact cause of multiple myeloma is not fully understood, but it is linked to genetic mutations and chromosomal abnormalities in plasma cells. Risk factors include age, male sex, African ancestry, family history of myeloma or other plasma cell disorders, prior history of monoclonal gammopathy of undetermined significance (MGUS), exposure to ionizing radiation, and possibly certain environmental toxins. Of particular interest among environmental factors is a statistically significant correlation between MM and exposure to a chemical called benzene, found in rubber, plastic, and some organic waste. People working in the rubber manufacturing business and those having agricultural exposure to synthetic organic chlorines have also shown an incidence higher than that of the general population. However, no specific cause-and-effect relationship has been demonstrated.

Symptoms vary but are often summarized by the CRAB criteria:

• C – Calcium elevation (hypercalcemia): Causes nausea, constipation, confusion, and kidney problems.

• R – Renal impairment: Due to light chain deposition and hypercalcemia, leading to kidney dysfunction.

• A – Anemia: Fatigue, weakness, pallor, and shortness of breath.

• B – Bone disease: Bone pain (especially in the spine and ribs), pathological fractures, and lytic bone lesions.
  Other symptoms include recurrent infections (due to immune suppression), weight loss, and neuropathy in some cases.

Multiple Myeloma is often not detected until symptoms appear. Bone pain comes from the characteristic multiple lesions in bone, often in the spinal column or the long bones of the legs, which are rich in haematapoetic (blood-producing) marrow. The lesions are caused by an Osteoclast Activating Factor (OAF) - causing calcium to leach from the bones into the blood stream - present in a protein M produced by malignant plasma cells in the marrow. Skeletal fractures are caused by a generalized decrease in bone density caused by the OAF and resulting in some degree of osteopenia or osteoporosis. 

In addition to complications with plasma cells, red blood cell anemia in MM patients is very common as the dysfunctional plasma cells proliferate within the marrow and displace ("squeeze out") the red cell progenitors. With fewer red cells being produced, and with red cells having a limited life span before requiring replacement, the total red cell count decreases, and with it the circulation of haemoglobin, which carries oxygen and attaches to the red blood.

Kidney function can become impaired as the higher levels of blood-borne calcium that has leached from the bone are filtered by the kidneys. This at times can result in a dull ache in the kidneys, providing another symptom. Eventually, should be kidneys become clogged with excess calcium, they can lose their ability to filter other toxins in the blood and excrete them in the urine, loading the circulatory system with substances toxic to the organs and tissues of the body.

The diagnosis of multiple myeloma is often made incidentally during routine blood tests for other conditions. Diagnosis is based on clinical features, laboratory findings, imaging, and bone marrow evaluation. It requires evidence of clonal plasma cells in the marrow (≥10%) or a biopsy-proven plasmacytoma, plus at least one myeloma-defining event such as CRAB features or specific biomarkers. For example, the existence of anemia and a high serum protein may suggest further testing. The diagnosis of Multiple Myeloma is done through a specific protocol of blood and urine test and an X-ray survey of the skeleton. The presence in the blood of a specific protein, a protein produced by malignant cells in the marrow, is needed for diagnosis. This may be what is called an "M-protein" or "Bence-Jones protein." The stage of disease (I, II, or III; and -a or -b) is determined by a study of the density of plasma cells in a sample of marrow and whether or not the kidney function has been affected by the disease.

• Blood tests: Serum protein electrophoresis (SPEP) and immunofixation to detect monoclonal antibody proteins; serum free light chain assay; complete blood count; calcium and creatinine levels.

• Urine tests: Urine protein electrophoresis (UPEP) to detect Bence Jones proteins.

• Bone marrow biopsy: To assess clonal plasma cell percentage and cytogenetic abnormalities.

• Imaging studies: Skeletal survey, low-dose CT, PET/CT, or MRI to detect lytic lesions and bone involvement.

Treatment depends on disease stage, patient age, and comorbidities. Chemotherapy and radiation treatment options are still available, but stem cell transplantation and more specific therapeutics have been developed for each individual patient (see CAR-T cell therapy). 

• Initial therapy: Combination regimens including proteasome inhibitors (bortezomib), immunomodulatory drugs (lenalidomide, thalidomide), and corticosteroids.

• Stem cell transplant: Eligible patients may undergo autologous stem cell transplantation after high-dose chemotherapy.

• Maintenance therapy: Lenalidomide or other agents may be used to prolong remission.

• Supportive care: Bisphosphonates for bone protection, erythropoiesis-stimulating agents for anemia, dialysis for kidney failure, and antibiotics for infections.

• Newer therapies: CAR-T cell therapy, monoclonal antibodies (daratumumab, elotuzumab), and novel targeted drugs for relapsed disease.

Multiple myeloma is generally considered incurable, but modern therapies have significantly improved survival. Median survival has increased to 5–10 years, depending on stage, cytogenetic risk, and response to therapy. Patients with high-risk genetic mutations or aggressive disease have poorer outcomes, while those with standard-risk disease can live for many years with treatment. The disease typically follows a relapsing-remitting course, requiring multiple lines of therapy over time.

1. Mayo Clinic - Multiple Myeloma

2. Cleveland Clinic - Multiple Myeloma

3. Multiple Myeloma Research Foundation