Multiple myeloma is a blood cancer that starts in plasma cells, a type of white blood cell that normally produces antibodies to fight infections. In myeloma, these plasma cells become cancerous, multiply uncontrollably in the bone marrow, and produce a dysfunctional protein that serves no immune purpose. About 36,000 new cases are expected in the United States in 2026, with an incidence rate of 7.4 per 100,000 people per year.
How Myeloma Develops in the Bone Marrow
Plasma cells go through a natural process called antibody class switching, where they learn to produce different types of antibodies. During this process, a genetic error can occur: a piece of a chromosome breaks off and reattaches in the wrong place, landing next to a gene that controls cell growth. This essentially turns on a permanent “grow” signal in that plasma cell, creating an immortal clone that keeps dividing.
Once these abnormal plasma cells take root in the bone marrow, they don’t just sit there passively. They attach to the surrounding support cells (called stromal cells) and trigger those cells to release a growth signal called interleukin-6. This creates a feedback loop: the myeloma cells stimulate their environment, and the environment feeds the myeloma cells right back. The cancer essentially builds its own support system. Over time, additional genetic mutations accumulate, allowing the cancer to grow more aggressively and eventually become independent of that bone marrow support network.
Precursor Conditions: MGUS and Smoldering Myeloma
Multiple myeloma almost always develops from a precursor condition called MGUS (monoclonal gammopathy of undetermined significance). In MGUS, abnormal plasma cells are present and producing that dysfunctional protein, but not in amounts large enough to cause symptoms or organ damage. On average, about 1% of people with MGUS progress to multiple myeloma each year. That risk doesn’t go away over time, which is why MGUS requires ongoing monitoring.
Between MGUS and full-blown myeloma sits an intermediate stage called smoldering myeloma, where there are more abnormal plasma cells and higher levels of the abnormal protein, but still no organ damage. The annual risk of progression from smoldering myeloma to active disease is significantly higher than MGUS, roughly 10% per year in the first five years after diagnosis. Some people with smoldering myeloma live years without ever needing treatment, while others progress within months.
Who Is at Higher Risk
Age is the strongest risk factor. Most people diagnosed with myeloma are 65 or older, and the disease is uncommon before age 50. Race plays a significant role as well. People of African descent develop myeloma at roughly two to three times the rate of people of European descent. This disparity starts early: the precursor condition MGUS is also more common in Black populations across all age groups, and by age 80, the prevalence of MGUS in African Americans is nearly double that of white Americans (8.6% versus roughly 4.5%). In contrast, incidence rates are lower in Japanese and Mexican American populations.
What Myeloma Does to the Body
The damage myeloma causes comes down to four main problems, sometimes remembered by the acronym CRAB: calcium elevation, renal (kidney) problems, anemia, and bone disease.
Bone destruction is the hallmark complication. Myeloma cells release chemical signals that activate osteoclasts, the cells responsible for breaking down bone. At the same time, they suppress the production of a natural brake on bone breakdown called osteoprotegerin. The result is that bone gets destroyed far faster than it can rebuild, leading to holes in the skeleton called lytic lesions. These most commonly appear in the spine, pelvis, ribs, and skull, and they cause pain, fractures, and sometimes spinal cord compression.
High calcium in the blood happens because all that bone breakdown releases calcium into the bloodstream. Levels above 11.0 mg/dL can cause confusion, excessive thirst, constipation, and nausea.
Kidney damage occurs when the abnormal proteins produced by myeloma cells clog and damage the tiny filtering tubes in the kidneys. High calcium levels compound the problem.
Anemia develops because the cancerous plasma cells crowd out the normal blood-forming cells in the bone marrow. A hemoglobin level below 10.0 g/dL is common at diagnosis, leading to fatigue, weakness, and shortness of breath.
How Myeloma Is Diagnosed
Diagnosis typically starts with blood and urine tests. A test called serum protein electrophoresis separates the proteins in your blood by size and charge. In myeloma, the abnormal protein (called M-protein) shows up as a distinctive sharp spike on the results graph. A more sensitive follow-up test called immunofixation can identify the exact type of abnormal protein being produced.
Additional bloodwork checks for the indirect signs of damage: calcium levels, kidney function, blood counts, and two key markers used for staging (beta-2 microglobulin and albumin). A bone marrow biopsy confirms the diagnosis by showing how many abnormal plasma cells are present and what genetic abnormalities they carry. Imaging, usually a CT scan or PET-CT, looks for lytic bone lesions throughout the skeleton.
Staging and What It Means for Prognosis
Myeloma is staged using the Revised International Staging System, which groups patients into three risk categories based on blood protein levels, genetic abnormalities in the cancer cells, and an enzyme called LDH that reflects how aggressively the disease is behaving.
- Stage I means lower levels of beta-2 microglobulin, normal albumin, no high-risk chromosome changes, and normal LDH. This group has the best outlook.
- Stage III means high beta-2 microglobulin combined with either high-risk genetic changes (specific deletions or translocations in the cancer’s DNA) or elevated LDH. This group faces a more aggressive disease course.
- Stage II is everything in between.
The high-risk genetic changes that matter most are a deletion on chromosome 17 and certain translocations involving chromosome 14. These abnormalities make the cancer harder to control and more likely to return after treatment.
Overall, the five-year relative survival rate for myeloma is 63.7%, based on data from 2016 to 2022. That number has improved dramatically over the past two decades thanks to new drug classes, and it continues to climb as newer therapies become available.
How Myeloma Is Treated
Treatment for myeloma has transformed since the early 2000s. The backbone of modern therapy combines drugs from several categories, each attacking the cancer through a different mechanism.
Proteasome inhibitors block a cellular recycling system that myeloma cells depend on heavily. When that system gets shut down, toxic waste proteins accumulate inside the cancer cell and kill it. The first drug in this class was approved in 2003, and newer versions now come in oral form, making treatment more convenient.
Immunomodulatory drugs work on multiple fronts: they change the bone marrow environment to make it less hospitable to myeloma cells, boost the immune system’s ability to recognize the cancer, and directly slow cancer cell growth. These are typically taken as pills.
Monoclonal antibodies are lab-made proteins that attach to specific targets on the surface of myeloma cells, flagging them for destruction by the immune system. One widely used antibody targets a protein called CD38, which is abundant on myeloma cells. Adding this antibody to standard drug combinations has significantly improved response rates.
For patients who are healthy enough, typically those under 70 without major organ problems, high-dose chemotherapy followed by a stem cell transplant remains a key part of initial treatment. The transplant isn’t a cure, but it deepens the response and extends the time before the disease returns.
CAR-T Cell Therapy for Relapsed Disease
When myeloma comes back after multiple rounds of treatment, a newer option called CAR-T cell therapy has shown remarkable results. In this approach, some of your own immune cells are collected, genetically reprogrammed in a lab to recognize a protein on myeloma cells called BCMA, and then infused back into your body as a living drug.
The first CAR-T therapy for myeloma was approved in 2021 for patients who had already been through at least four prior treatments. In clinical trials, 81% of heavily pretreated patients responded to the highest dose, and about 39% achieved a complete response, meaning no detectable disease. Even in patients whose myeloma returned within 18 months of their initial treatment (a group with a particularly poor prognosis), the response rate was nearly 84%, with about 46% reaching complete response.
The durability of these responses is still being studied. Median progression-free survival in trials has been around 11 to 12 months, which may sound modest, but for patients who have exhausted other options, this represents a meaningful period of disease control. Newer CAR-T products and earlier use in the treatment sequence are pushing these numbers higher.
Living With Myeloma
Myeloma is currently considered treatable but not curable for most people. The typical pattern involves periods of treatment followed by remission, then eventually relapse, requiring a new treatment approach. Each successive remission tends to be shorter, though the growing number of available drug classes means many patients cycle through several effective therapies over years or even decades.
Bone health is an ongoing concern. Most patients receive bone-strengthening medications to slow further skeletal damage and reduce fracture risk. Managing kidney function, preventing infections (since both the disease and its treatments weaken the immune system), and monitoring blood counts are all part of routine care. Many people with myeloma maintain active lives between treatment cycles, especially during remission periods when the disease is well controlled.