How Rare Is Multiple Myeloma and Who Is Most at Risk

Multiple myeloma is uncommon but far from vanishingly rare. It accounts for roughly 10% of all blood cancers and about 1% of all cancers overall, with approximately 155,700 new cases diagnosed worldwide in 2019.¹² The risk profile for this disease is layered: age, sex, race, body weight, environmental exposures, and even a person’s history of autoimmune disease all feed into who gets it. Some of those factors are well understood, while others are still being untangled.

Where It Falls on the Rarity Spectrum

If you picture all cancers as a crowd, myeloma is not the face you would recognize first. Breast, lung, prostate, and colon cancers each affect far more people. But among blood cancers, myeloma is a significant player, making up about one in ten cases.¹ In the United States, it is the second most common blood cancer after non-Hodgkin lymphoma, with an estimated 35,000 or so new diagnoses each year. Globally, Europe has the highest age-adjusted incidence rate, while North America sees the highest mortality rate.³ Lower-income regions tend to report fewer cases, but that gap likely reflects underdiagnosis and limited cancer registries rather than true protection from the disease.

Age Is the Strongest Single Risk Factor

Multiple myeloma is overwhelmingly a disease of older adults. The median age at diagnosis is around 69, and fewer than 5% of cases occur before age 45. Being diagnosed before 40 is genuinely rare, and those young patients tend to have distinctive biology that is still being studied.⁴ The age pattern has an important practical consequence: many early symptoms of myeloma, such as bone pain, fatigue, and mild anemia, overlap with conditions people expect to develop as they age. That overlap contributes to diagnostic delays, which are longer for myeloma than for most other cancers.

In the UK, research found that 37% of myeloma patients were diagnosed through emergency presentations rather than through routine care. The individual symptoms that myeloma causes in a primary care setting carry low predictive value on their own, making it easy for both patients and doctors to attribute them to aging or something benign.⁵ Persistent unexplained back pain, recurrent infections, kidney problems, and blood tests showing anemia or elevated calcium together form a pattern worth investigating, especially in someone over 60.

The Sex Gap

Men get myeloma more often than women. Globally, about 54% of cases in 2019 were male.² In clinical trial populations, the split is even more skewed, roughly 58% male and 42% female.⁶ The male-female incidence and mortality gap holds across age groups and racial and ethnic categories.⁷

Interestingly, though, once men and women are diagnosed and treated, their outcomes look similar. A large trial of nearly 3,900 patients found that progression-free survival was about 25 months for men and 24 months for women, with overall survival at 67 months for men and 70 months for women, neither difference being statistically meaningful.⁶ Female patients did, however, show more frequent high-risk genetic abnormalities, including a higher rate of del(17p) and t(14;16), which are markers associated with more aggressive disease. The fact that survival was equivalent despite this biological disadvantage suggests that sex interacts with treatment response in ways researchers are still sorting out.

Racial Disparities in Incidence and Access

Black Americans develop multiple myeloma at roughly double the rate of white Americans. This is one of the most striking racial disparities in all of oncology.⁸ The elevated risk appears to be partly rooted in genetic ancestry. Genome-wide studies have identified specific risk regions, including a variant in the TNFRSF13B gene on chromosome 17, that differ in frequency between people of African and European descent.⁹ Black patients also carry different patterns of chromosomal rearrangements: they are more likely to have certain translocations, while white patients are more likely to carry others. These differences in tumor biology have implications for prognosis and treatment selection.

Compounding the biological differences is a troubling gap in healthcare access. Black individuals are underrepresented in clinical trials for new myeloma treatments. A geographic analysis found that only about 36% of Black Americans lived in a county that had an open trial for CAR-T cell therapy, one of the most promising newer approaches to myeloma.¹⁰ Among the ten states with the highest proportion of Black residents, six had either no trial openings or fewer than three for CAR-T or bispecific antibody treatments. When the population most affected by a disease has the least access to cutting-edge therapies, the disparity in outcomes is more than biological.

The Precursor Conditions Most People Have Never Heard Of

Almost every case of multiple myeloma is preceded by a condition called monoclonal gammopathy of undetermined significance, or MGUS. In MGUS, the bone marrow produces an abnormal protein but not at levels that cause organ damage. A landmark study in Olmsted County, Minnesota, found MGUS in about 3.2% of people over the age of 50.¹¹ That means MGUS is common, far more common than myeloma itself. But the rate at which MGUS progresses to myeloma or a related malignancy is only about 1% per year.¹² Over 25 years of follow-up, roughly 30% of people with MGUS had experienced progression. Most people with MGUS will die of something else entirely.

Between MGUS and full-blown myeloma sits another intermediate stage called smoldering multiple myeloma. At this stage, the abnormal protein levels and proportion of bone marrow plasma cells are higher, but the person still has no symptoms or organ damage. The clinical question of whether to treat smoldering myeloma has been hotly debated. A recent trial found that treating high-risk smoldering patients with the drug daratumumab cut the risk of progression or death by about half compared to just watching and waiting, with five-year progression-free survival of 63% versus 41%.¹³ This result is reshaping clinical practice, because it suggests that catching and intervening at the smoldering stage could delay or possibly prevent progression in a substantial fraction of people.

Obesity as a Modifiable Risk Factor

Of all the lifestyle factors studied in relation to myeloma, excess body weight has the strongest and most consistent association. Obesity is considered the only well-established modifiable risk factor for the disease.¹⁴ A large study estimated an 18% increase in myeloma risk for every five-unit increase in body mass index. People with severe obesity, meaning a BMI of 40 or above, had nearly twice the risk compared to people with a normal BMI.¹⁵ The association was especially pronounced among Black men, though that estimate was based on a small subgroup.

The link between weight and myeloma extends beyond just BMI at a single point in time. Research has found that people with a pattern of gaining weight over their adult lives, and especially those with extreme weight cycling, face elevated risk compared to those who maintain a stable, lean weight throughout life.¹⁶ Pooled analyses have also found that overweight and obese individuals face higher myeloma-specific mortality, with a roughly 50% higher death rate for people who are obese at the time of diagnosis.¹⁴ The mechanisms likely involve chronic inflammation, altered hormone signaling, and changes in the bone marrow microenvironment that favor plasma cell survival. Myeloma cells depend heavily on signals from their surrounding microenvironment, and obesity changes that environment in ways that appear to benefit malignant cells.¹⁷

Environmental and Occupational Exposures

Certain chemical exposures raise myeloma risk, with the best-documented being Agent Orange and related herbicides containing dioxins. A study of Vietnam-era Ranch Hand veterans, who handled Agent Orange directly, found that the prevalence of MGUS among them was more than double that of comparison veterans.¹⁸ A separate population-based study of Vietnam War veterans found that those with high Agent Orange exposure had a nearly 50% higher rate of progression from MGUS to myeloma.¹⁹ The contaminating chemical in Agent Orange, a dioxin called TCDD, appears to promote myeloma through pathways involving oxidative stress and DNA damage.²⁰

The occupational risk extends beyond veterans. Firefighters exposed to the World Trade Center disaster showed an age-adjusted prevalence of MGUS that was roughly 1.8 times higher than a comparable general population, and their rate of a specific subtype called light-chain MGUS was more than three times higher.²¹ More broadly, pesticides, combustion byproducts, and various industrial chemicals have all been associated with elevated risk in epidemiologic studies.²⁰ The common thread seems to be chronic, low-level exposure to chemicals that cause DNA damage and persistent immune stimulation.

Family History and Genetic Susceptibility

Having a first-degree relative with myeloma or a related blood disorder increases your own risk. Family pedigree studies, case-control analyses, and the racial disparities described above all point toward an inherited susceptibility that goes beyond shared environment.²² Genome-wide studies have identified several regions across the genome that contribute to myeloma susceptibility, including spots on chromosomes 3, 7, and 8.²² More recent work has explored both common low-risk variants and rarer high-impact variants that run in families with unusually high myeloma rates.²³

None of these genetic variants, on their own, strongly determine whether someone will develop myeloma. The disease appears to result from multiple small genetic pushes interacting with age, immune function, and environmental exposures. People with a family history of myeloma or MGUS should mention it to their doctor, particularly if they develop symptoms like unexplained anemia or elevated total protein on a blood test. Routine screening of the general population is not currently recommended, but understanding your family history can prompt earlier investigation when something seems off.

Autoimmune Conditions and Chronic Immune Stimulation

People with certain autoimmune or chronic inflammatory conditions face a modestly higher risk of developing myeloma. A large study of male veterans found that prior autoimmune, infectious, and inflammatory disorders were each associated with roughly 15-30% increases in myeloma risk.²⁴ The specific conditions with the strongest links included autoimmune hemolytic anemia, systemic sclerosis, and ankylosing spondylitis.²⁵ The relationship works both ways: people with MGUS and myeloma also show a higher-than-expected rate of autoimmune diseases compared to the general population.²⁶

The connection probably reflects the fact that chronic immune activation can push antibody-producing cells to proliferate more frequently, increasing the chance of acquiring mutations that eventually become malignant. This does not mean that having an autoimmune condition makes myeloma likely. The absolute increase in risk is small. But for clinicians, it adds another data point to consider when evaluating patients who present with unusual blood test results.

How Survival Has Changed

A diagnosis of multiple myeloma today carries a very different outlook than it did 20 years ago. Before about 2000, the median survival from diagnosis was roughly 30 months. After the introduction of newer drugs like thalidomide, lenalidomide, and bortezomib, median overall survival climbed to about 45 months.²⁷ The improvement has continued with the addition of monoclonal antibodies and, more recently, CAR-T cell therapies and bispecific antibodies. Five-year survival rates have risen steadily, and early mortality has declined.²⁸

Even after relapse, outcomes are better than they used to be. Among patients who relapsed after stem cell transplant, those who relapsed after 2000 survived a median of about 24 months from relapse compared to roughly 12 months for those who relapsed before the newer drugs were available. Patients who received at least one of the newer agents had a median of about 31 months from relapse.²⁷ Yet these gains are not distributed equally. Racial and social inequities continue to limit who benefits from the most advanced treatments, and access to clinical trials remains heavily concentrated in certain geographic areas.²⁹

The Genomic Complexity Behind the Disease

One reason myeloma behaves differently from patient to patient is its extraordinary genetic complexity. A comprehensive genomic study identified 61 driver genes across hundreds of myeloma samples, with roughly 87% of all cases harboring at least one driver mutation. The average patient carried about two driver mutations, but the specific combination varied widely.³⁰ Commonly mutated genes include KRAS, NRAS, and DIS3, but dozens of less frequent mutations also contribute, and many of these arise late in the disease’s development, appearing in subgroups of cells rather than in the original tumor clone.

This internal diversity is one reason myeloma is difficult to cure outright. A treatment that kills the dominant population of cancer cells may leave behind a subclone carrying a resistance mutation that then grows to fill the void. The field increasingly approaches myeloma as a disease requiring layered, sequential therapies rather than a single decisive strike. Researchers continue to map out which mutations drive the disease forward versus which are incidental passengers, with the goal of identifying better targets for therapy.³¹

Prior Blood Cancers and Secondary Myeloma

A less well-known risk factor is having had certain other blood cancers before developing myeloma. In a large case-control analysis, a prior diagnosis of a myeloproliferative neoplasm, particularly primary myelofibrosis, was associated with roughly 3.6 times the odds of subsequently developing myeloma. A prior diagnosis of Hodgkin lymphoma carried a similar elevation, at about 3.7 times the odds.³² Whether these associations reflect shared genetic susceptibility, the effect of prior treatments on the bone marrow, or simply heightened surveillance in people already being monitored for blood disorders remains an open question. For the overall cancer population, having had any prior malignancy did not increase myeloma odds, meaning this risk is specific to a small subset of blood conditions rather than a general cancer-survivor phenomenon.