Smoldering Multiple Myeloma Progression Explained

Smoldering Multiple Myeloma Progression: How Fast Does SMM Become Active Myeloma?

Smoldering Multiple Myeloma Progression: How Fast Does SMM Become Active Myeloma? Smoldering multiple myeloma (SMM) does not progress at the same rate in every patient. Some people progress to active multiple myeloma relatively quickly. Others can live with stable smoldering myeloma for many years without developing symptomatic disease.

That difference is one of the most important things for anyone diagnosed with SMM to understand. The question is no longer simply:

“Do I have smoldering multiple myeloma?”

A better question is:

“What is my individual risk of progression, and is my disease stable or evolving?”

That distinction can influence how frequently you should be monitored and whether active surveillance or early treatment should be discussed.

I am a long-term multiple myeloma survivor. When I was diagnosed in 1994, doctors understood far less about MGUS, smoldering myeloma, biomarkers, imaging, and progression risk than they do today.

Modern SMM management is increasingly about risk stratification rather than treating every patient with the same diagnosis the same way.

I have come to believe that therapy-induced side effects can be life-threatening while ruining quality of life. For example, more than half of all MMers die of infections. Both MM itself and various chemotherapy regimens cause immunosuppression. Consider therapies shown to reduce possible side effects.

Scroll down the page and post a question or a comment if there’s anything you’d like to know about MM.

Good luck,

David Emerson

Concepts Central to Managing Your Cancer-

Possible Therapies-

What Is Smoldering Multiple Myeloma?

Smoldering multiple myeloma is an asymptomatic plasma-cell disorder between monoclonal gammopathy of undetermined significance (MGUS) and active multiple myeloma.

A patient with SMM has a measurable population of abnormal plasma cells but does not have the myeloma-defining organ damage or biomarkers required for a diagnosis of active multiple myeloma.

Active MM is diagnosed when clonal plasma-cell disease is accompanied by one or more myeloma-defining events, including the familiar CRAB features:

C — Hypercalcemia
R — Renal/kidney impairment
A — Anemia
B — Bone lesions

Modern diagnostic criteria also include specific biomarkers sometimes called SLiM criteria, including very high bone marrow plasma-cell involvement, a markedly abnormal free light-chain ratio under specified conditions, or more than one focal lesion on MRI.

This distinction matters because someone meeting myeloma-defining criteria no longer has SMM and should be evaluated as having active multiple myeloma.

Research:
Multiple Myeloma: 2026 Update on Diagnosis, Risk-Stratification and Management — PubMed

How Fast Does Smoldering Multiple Myeloma Progress?

There is no single progression rate that accurately describes every SMM patient.

Historically, SMM has often been described as progressing to multiple myeloma at approximately:

10% per year during the first five years
approximately 3% per year during the next five years
approximately 1%–2% annually thereafter

But those averages can be misleading.

SMM is extremely heterogeneous.

One person may have biologically indolent disease resembling MGUS. Another patient diagnosed with SMM may already have plasma-cell disease that is biologically close to active myeloma.

A large International Myeloma Working Group analysis found a median time to progression of approximately 6.4 years across the entire SMM population, but individual risks varied enormously.

That is why modern oncology increasingly focuses on individual progression risk rather than an average SMM progression rate.

Research:
International Myeloma Working Group SMM Risk-Stratification Model — PubMed

The 2/20/20 Smoldering Myeloma Risk Model

One widely used approach is the International Myeloma Working Group 2/20/20 model.

It considers three major risk factors:

1. M-protein greater than 2 g/dL

The amount of monoclonal protein circulating in the blood helps estimate plasma-cell disease burden.

2. Bone-marrow plasma cells greater than 20%

Greater clonal plasma-cell involvement of the bone marrow is associated with greater progression risk.

3. Involved/uninvolved free-light-chain ratio greater than 20

A substantially abnormal serum free-light-chain ratio is another indication of greater clonal activity.

In the original IMWG analysis, patients were separated into three groups:

2/20/20 Risk Factors	Approximate 2-Year Progression Risk
None	6%
One	18%
Two or three	44%

Adding certain cytogenetic abnormalities can further refine risk.

These include abnormalities such as:

t(4;14)
t(14;16)
+1q
del13q/monosomy 13

This is why a diagnosis of “smoldering myeloma” alone does not tell you enough.

Two people can both have SMM while facing very different probabilities of progression.

Research:
IMWG 2/20/20 Smoldering Multiple Myeloma Model — PMC

Stable Versus Evolving Smoldering Myeloma

There is another concept that I believe SMM patients should understand:

Is your disease stable, or is it evolving?

A single M-spike gives you a snapshot. Repeated testing gives you a movie. Researchers have found that an evolving M-protein pattern can provide important information about progression risk.

For example, increases in M-protein over time—particularly when accompanied by changes such as falling hemoglobin—have been associated with substantially greater progression risk.

A 2024 study found that incorporating an evolving M-protein pattern into the 2/20/20 model further separated patients into groups with dramatically different progression risks.

Research:
Evolving M-Protein Improves the IMWG 2/20/20 Classification — PMC

For a detailed explanation of this important biomarker, see:

M-Spike in Multiple Myeloma: What Does Your Monoclonal Protein Level Mean? — PeopleBeatingCancer

“Slow” Smoldering Myeloma Can Be Very Different From High-Risk SMM

This is the part of SMM that I think patients sometimes miss.

If your:

M-spike remains relatively stable,
free-light-chain ratio remains stable,
hemoglobin remains stable,
kidney function remains normal,
calcium remains normal,
imaging remains negative,
and bone-marrow disease burden is relatively low,

your clinical situation can be very different from someone whose biomarkers are steadily worsening. This does not mean stable SMM cannot eventually progress. It means that trajectory matters.

The 2026 review of SMM diagnosis and management in Nature Reviews Clinical Oncology emphasizes this heterogeneity: low-risk SMM can behave indolently, whereas approximately 40%–50% of patients classified as high-risk can progress within two years.

Research:
Diagnosis, Risk Stratification and Management of Smouldering Multiple Myeloma — Nature Reviews Clinical Oncology

Should Smoldering Multiple Myeloma Be Treated?

This question has changed considerably since I originally wrote this article. For decades, the standard approach to SMM was essentially:

Watch and wait.

There was a good reason for that approach. Treating someone who feels healthy exposes that person to drug toxicity, inconvenience, financial cost, and treatment burden. And many patients with lower-risk SMM may remain stable for years.

But the equation changes when the probability of developing active MM becomes high. The goal of early treatment is to intervene before irreversible myeloma-related organ damage occurs, particularly bone damage, kidney injury or other complications.

Daratumumab and High-Risk Smoldering Multiple Myeloma

The AQUILA phase 3 trial substantially changed this discussion.

Researchers randomly assigned 390 patients with high-risk SMM to either:

subcutaneous daratumumab, or
active monitoring.

After a median follow-up of approximately 65 months, daratumumab reduced the risk of disease progression or death by approximately 51% compared with active monitoring.

Five-year progression-free survival was:

63.1% with daratumumab
40.8% with active monitoring

Five-year overall survival was:

93.0% with daratumumab
86.9% with active monitoring

Treatment was not free of side effects, although investigators reported no unexpected safety concerns.

Research:
Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma — PubMed

Based on AQUILA, the FDA approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) in November 2025 for adults with high-risk smoldering multiple myeloma.

FDA:
FDA Approval of Daratumumab for High-Risk Smoldering Multiple Myeloma

That is an important change from when this article was originally written.

But There Is Still an Important Debate

FDA approval does not mean that every person diagnosed with SMM should begin treatment. One of the central problems is defining “high risk.”

A 2026 study compared the high-risk criteria used in AQUILA with the IMWG 2/20/20 model. The researchers found that the AQUILA criteria identified substantially more people as high risk than the 2/20/20 model.

In the clinical cohort studied:

AQUILA-defined high-risk patients had approximately a 27% two-year progression risk.
2/20/20-defined high-risk patients had approximately a 44% two-year progression risk.

In other words:

The definition of “high-risk SMM” matters enormously.

Research:
Identifying High-Risk Smoldering Multiple Myeloma for Early Intervention — PubMed

A major 2026 review therefore concluded that for patients with high-risk SMM, both early therapeutic intervention and active surveillance can be reasonable options, depending on the individual’s risk and preferences.

That is a much more nuanced position than either:

“Never treat smoldering myeloma.”

“High-risk smoldering myeloma should always be treated.”

The Question I Would Ask: What Is My Actual Risk?

If I were diagnosed with SMM today, I would want my hematologist to help me answer several questions before deciding about treatment:

What is my 2/20/20 risk category?
What percentage of my bone marrow consists of clonal plasma cells?
What is my current M-spike, and how has it changed over time?
What is my involved/uninvolved free light-chain ratio?
Do I have high-risk cytogenetic abnormalities?
Is my hemoglobin stable?
Are my kidney function and calcium normal?
Have I had appropriate whole-body imaging?
Is my SMM stable or evolving?
What is my estimated risk of progression over the next two years?
If treatment is recommended, what evidence shows that someone with my particular risk profile benefits?
What are the short- and long-term risks of treatment versus continued surveillance?

Those questions turn a vague diagnosis of “smoldering myeloma” into a much more useful discussion about individual risk.

Monitoring Matters

Choosing active surveillance does not mean doing nothing. It means watching carefully for biological changes that could indicate progression.

Monitoring can include:

serum protein electrophoresis (SPEP)
M-protein/M-spike
serum free light chains
quantitative immunoglobulins
complete blood count
creatinine/kidney function
calcium
symptoms
appropriate imaging
and, when clinically indicated, repeat bone-marrow evaluation

The frequency should be individualized according to progression risk and how stable the patient’s disease has been.

Don’t Ignore Bone Health

Myeloma can damage bone before a patient experiences dramatic symptoms. Modern imaging is therefore an important part of distinguishing SMM from active multiple myeloma. Patients should also understand bone density, vitamin D status, exercise, fall prevention, and other factors affecting skeletal health.

For a detailed discussion, see:

Bone Health in Multiple Myeloma: What Patients Need to Know — PeopleBeatingCancer

Can Lifestyle or Integrative Therapies Slow SMM Progression?

This question interests many MGUS and SMM patients—including me. Diet, exercise, metabolic health and certain nutritional compounds are being investigated in plasma-cell disorders.

However, an important distinction must be made:

No diet, supplement, or lifestyle program has been proven to prevent SMM from progressing to multiple myeloma.

That does not make lifestyle irrelevant.

Exercise, maintaining a healthy body composition, avoiding smoking, eating a nutritious plant-forward diet, and addressing cardiovascular and metabolic risk can contribute to overall health and potentially make a patient better prepared if treatment eventually becomes necessary. (prehabilitation)

Some compounds, including curcumin, have generated preliminary research in MGUS/SMM, but this evidence should not be confused with proof that supplementation prevents multiple myeloma.

For more discussion:

MGUS & SMM: Reduce Risk of Progression to Multiple Myeloma — PeopleBeatingCancer

And:

Natural Smoldering Multiple Myeloma Therapies? — PeopleBeatingCancer

PeopleBeatingCancer Evidence Rating

Approach	PBC Evidence Rating	What the Evidence Shows
Risk stratification with 2/20/20	🟢 Strong clinical evidence	Validated method for estimating SMM progression risk
Monitoring M-spike/FLC trends	🟢 Strong clinical evidence	Evolving biomarkers can identify increasing progression risk
Modern imaging	🟢 Strong clinical evidence	Important for excluding active MM and improving risk assessment
Daratumumab for appropriately selected high-risk SMM	🟢 Randomized phase 3/FDA-approved	Delays progression compared with active monitoring in AQUILA
Active surveillance	🟢 Established clinical approach	Remains reasonable, particularly when progression risk is lower or after individualized risk-benefit discussion
Diet/exercise	🟡 Supportive/emerging evidence	Valuable for overall health; not proven to prevent SMM progression
Curcumin/other supplements	🟠 Preliminary evidence	Interesting biomarker and laboratory data but insufficient evidence to establish prevention of MM

The Bottom Line

Smoldering multiple myeloma is not one disease with one predictable course. It is a spectrum.

Some patients have relatively slow, stable SMM and may remain asymptomatic for many years. Others have evolving, high-risk SMM that is much more likely to become active multiple myeloma.

That distinction matters more today because patients with genuinely high-risk disease now have an FDA-approved early-treatment option. For me, the central question is therefore not simply:

“Should smoldering multiple myeloma be treated?”

It is:

“How likely is this particular patient’s smoldering myeloma to progress—and what are the risks and benefits of treating now versus continuing careful surveillance?”

That is a conversation worth having with a hematologist or myeloma specialist before making a treatment decision.

Triple Combo Therapy May Slow Smoldering Multiple Myeloma Progression into Overt Myeloma, Phase 2 Trial Shows

“Early treatment with a triple combination therapy containing Empliciti(elotuzumab), Revlimid (lenalidomide), and dexamethasone in patients with smoldering multiple myeloma — a precursor of multiple myeloma — may halt the disease’s progression into the full-blown condition, a Phase 2 trial shows…

Recent studies have shown that early treatment of smoldering myeloma may delay or prevent the progression into full-blown disease, and researchers have been looking for effective treatments to use in these patients…

The study’s primary goal was to determine the proportion of patients who had not progressed two years after starting treatment. Secondary endpoints included response rate, time to progression, overall survival, and safety of the combination therapy… the triple combination reduced disease burden in 84% of patients — including 6% complete responses, 37% very good partial responses, and 41% partial responses. An additional 10% of patients had minimal responses and 3% saw their disease stabilize.

Smoldering Multiple Myeloma Progression Smoldering Multiple Myeloma Progression Smoldering Multiple Myeloma Progression

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