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Myeloma staging: how ISS and R-ISS work | CION Cancer Clinics
Myeloma is staged I, II or III from blood and marrow tests, not from how far a lump has spread. The ISS uses beta-2 microglobulin and albumin. The Revised ISS, or R-ISS, adds LDH and high-risk chromosome changes from the marrow. There is no stage IV. The stage describes risk at diagnosis and does not change as treatment works. This page explains each stage and its limits. At CION Cancer Clinics, our haematology team plans myeloma and lymphoma care with you, discussed at a tumour board and explained in plain words.
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Medically reviewed by Dr. Basudev PokhrelConsultant Haematologist · last reviewed September 2026, next review due September 2027
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On this page
- What do ISS and R-ISS stages mean in myeloma?
- How is the ISS stage worked out?
- What does the R-ISS add, stage by stage?
- Which tests do you need before a stage can be given?
- What can the stage not tell you?
- What do families often misunderstand about myeloma stage?
- Which staging words will you see?
- Common questions about myeloma staging
The short answer
What do ISS and R-ISS stages mean in myeloma?
Myeloma is staged I, II or III using blood tests, not by how far a lump has spread. The ISS uses two blood proteins, beta-2 microglobulin and albumin. The R-ISS, or Revised ISS, adds LDH and the chromosome results from the bone marrow, and is the version most haematologists use today.
Why myeloma is staged differently
In most cancers, stage describes size and spread. Myeloma is already in the marrow of many bones when it is found, so that approach tells you little. Instead, the stage describes how much disease there is and how it is likely to behave, using markers measured in blood and marrow cells.
What the stage is used for
It helps your team describe your risk group, compare your situation with the research that treatment plans are based on, and decide how closely to watch you. It is one input into the plan, alongside your fitness, kidney function and wishes.
Stage III is not the same as "stage 4" elsewhere
There is no stage IV in myeloma. Stage III means higher-risk features are present. It does not mean the disease has spread to organs the way stage 4 does in breast or lung cancer, and it is still treated with the aim of good control.
Why a stage on paper can feel frightening
Families often see "stage III" on a report late at night and assume the worst. Please do not. The label was built to compare groups in research, not to predict one person's future. Bring the report to your haematologist and ask what it means for your own plan.
The original system
How is the ISS stage worked out?
Two blood tests, taken at diagnosis. Reference ranges differ between laboratories, so your team reads them against your own lab.
ISS stage
What the blood tests show
Stage I
Beta-2 microglobulin below 3.5 (in mg/L) and albumin 3.5 (in g/dL) or higher
Stage II
Results that fit neither stage I nor stage III
Stage III
Beta-2 microglobulin 5.5 (in mg/L) or higher, whatever the albumin
Not sure whether this applies to you?
Ask an oncologistThe revised system
What does the R-ISS add, stage by stage?
R-ISS keeps the ISS and adds two more pieces of information: LDH, a blood enzyme, and high-risk chromosome changes found by FISH testing on the marrow.
R-ISS stage I
ISS stage I, a normal LDH, and no high-risk chromosome changes. All three must be true.
What it usually means
- Lower-risk disease at diagnosis
- Still needs full treatment if active
R-ISS stage II
Anyone who is not stage I or stage III. This is the largest group, and it is broad: people in it can have quite different disease.
Ask which features placed you here. It matters more than the label.R-ISS stage III
ISS stage III together with either a high LDH or a high-risk chromosome change.
High-risk changes counted
- del(17p)
- t(4;14)
- t(14;16)
The newer R2-ISS
A later update gives points to each risk factor and also counts extra copies of chromosome 1q. Some reports now use it. The idea is the same: more risk factors, higher group.
Putting it together
Which tests do you need before a stage can be given?
Beta-2 microglobulin and albumin
Simple blood tests, usually done in the first round of tests. They give the ISS stage straight away.
LDH
Another blood test. A high level can mean faster-growing disease, but it also rises with muscle injury and some other illnesses, so it is read with care.
FISH on the marrow sample
Chromosome tests on plasma cells from the bone marrow test. Results can take longer than the blood tests, so the full R-ISS stage may come a little later.
Your haematologist combines them
The stage is written in your notes at diagnosis. It is not usually recalculated each time the blood tests change. Ask for a copy of the results used, so any second opinion starts from the same numbers.
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Being straight with you
What can the stage not tell you?
The stage cannot tell you how long you will live or how well your treatment will work. It describes groups of people in research studies, and every group contains people who do much better or worse than the average.
What else shapes the outlook
How deep the response to treatment is, whether you can have a stem cell transplant, kidney function, other illnesses and how well you manage the side effects all matter. Some of these change over time. The stage at diagnosis does not.
Who stage alone does not suit as a guide
Older or frail people are often better described by a fitness assessment than by stage. Someone at stage I who is very frail may need a gentler plan than a fit person at stage III. People with kidney failure can have a high beta-2 microglobulin partly because weak kidneys do not clear it.
Where to take your questions
Your own haematologist, with your marrow report and blood results in front of them, is the only one who can explain what your stage means for you. Ask them directly.
Commonly believed
What do families often misunderstand about myeloma stage?
"Stage III means it is too late to treat."
Stage III describes higher-risk features, not a point past which treatment stops. People at every stage are offered treatment aimed at control, and many respond well.
"The stage will go down as treatment works."
Stage is set at diagnosis and does not change. Response to treatment is tracked with different words, such as partial or complete response.
"Stage I means we can skip treatment."
Whether treatment starts depends on damage to bones, kidneys and blood, not on stage. Active myeloma at stage I still needs treatment.
"We found a survival number online for this stage."
Those figures come from older studies and large groups. They cannot predict one person's course, and newer treatments have changed the picture since.
On your report
Which staging words will you see?
- Beta-2 microglobulin
- A small protein shed by cells. Higher levels suggest more myeloma, or weaker kidneys.
- Albumin
- The main blood protein made by the liver. Lower levels go with more active disease and general illness.
- LDH
- An enzyme released when cells break down. A high level adds risk in R-ISS.
- FISH
- A marrow test that looks for specific chromosome changes in the myeloma cells.
- Standard risk and high risk
- Labels for chromosome findings. High risk means the disease tends to return sooner.
Questions we are asked
Common questions about myeloma staging
Which is more accurate, ISS or R-ISS?
R-ISS uses more information, so it separates risk groups better and is preferred where chromosome tests are available. ISS is still useful when FISH results are not yet back or could not be done. Your report may show both, and that is normal.
Why is my stage not on the first report?
The blood tests for ISS are quick, but the marrow chromosome tests take longer. Your haematologist may wait for all the results before giving an R-ISS stage. Treatment does not have to wait for the stage if the myeloma is already causing damage.
Can the stage change later?
The stage given at diagnosis stays the same. If myeloma returns, new tests may show new chromosome changes, and your team will describe the risk at that point. They will use that information without formally restaging you.
My mother's kidneys are weak. Does that affect her stage?
It can. Weak kidneys raise beta-2 microglobulin because the kidneys normally clear it. That can push the stage up even when the myeloma itself is not large. Your haematologist will take kidney function into account when explaining what the stage means for her.
Does the stage decide the treatment?
Not on its own. Treatment is chosen mainly by fitness, kidney function, chromosome risk and whether a transplant is possible. The stage helps describe risk, but two people at the same stage can get different plans for good reasons.
What if FISH testing was not done?
Then only the ISS stage can be given. Ask whether the stored marrow sample can still be tested, or whether FISH can be included in a future marrow test. CION's team can tell you where the test can be arranged if it is not available locally.
Is stage II good or bad?
Neither. It is the middle group and covers a wide range of people. Ask which results placed you in stage II, whether any high-risk chromosome change was found, and how your team plans to watch for response. Those answers tell you more than the number.
What should we ask the haematologist about staging?
Ask which staging system was used, what each test result was, whether FISH found any high-risk change, and how the stage affects the plan. Ask what the stage does not tell you. Write the answers down so the whole family has the same picture.
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Dr. Basudev Pokhrel reviews blood counts, transfusion needs and blood disorders, and works with the CION tumour board on blood cancers.
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Sources
- American Cancer Society — Multiple Myeloma Stages
- Cancer.Net — Multiple Myeloma: Stages and Groups
- National Cancer Institute — Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ) - Health Professional Version
- Cancer Research UK — Myeloma
This page is general information, not a prescription. Do not change or stop any treatment based on what you read here. If anything is worrying you, contact your own treating team — or call our helpline and we will help you reach the right specialist.
Keep reading
Related pages
High-Risk Cytogenetics in MyelomaThe chromosome changes that move R-ISS stageThe CRAB Criteria: How Myeloma Is DiagnosedStage is separate from the decision to treatAm I Eligible for a Stem Cell Transplant?Fitness often matters more than stage for the planMyeloma Explained: What It Does to Bones, Kidneys and BloodBackground if the diagnosis is new
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