# Symptoms and stages of multiple myeloma
Multiple myeloma does not progress the same way for everyone, but there are clear stages in which the disease progresses. This description covers what typically happens in each stage, which symptoms occur, and what that means for daily life. The condition can progress at different speeds.
Stage 1: Silent stage (MGUS and smouldering myeloma)
Before multiple myeloma fully manifests, years can pass in which altered blood cells are present but cause hardly any symptoms. This is called the "silent stage".
**What happens in the body:**
Plasma cell-like cells multiply in the bone marrow and produce abnormal proteins (paraproteins), but not yet in large enough quantities to cause serious damage. This stage is called MGUS (monoclonal gammopathy of undetermined significance) or smouldering myeloma, depending on how many cells are already present.
**Symptoms:**
Usually *no* symptoms. Many people are only diagnosed by chance when blood tests are done for a completely different reason. Sometimes patients feel tired, but this can have many causes and is not always attributed to this stage.
**What this means for daily life: **
For many people, nothing noticeable changes. They feel healthy, can continue their normal activities, and may not even know they have these cells. Some do receive follow-up care requiring check-up visits.
**Figures about this phase: **
Not everyone with MGUS or smouldering myeloma will ever develop true myeloma; some remain stable without progression. The average time before someone with MGUS progresses to myeloma is highly variable — from never to several years. In previous decades, MGUS showed approximately 1% progression per year, but this depends heavily on risk factors.
Stage 2: Active/newly diagnosed myeloma
By the time multiple myeloma is officially diagnosed, usually a considerable amount of abnormal plasma cells has already established itself in the body. Doctors call this "newly diagnosed myeloma".
**Symptoms in this phase: **
**Bone pain and bone-related problems**
This is the most common complaint. The abnormal cells in the bone marrow produce substances that break down bone tissue faster than it is formed. This leads to:
- Severe pain in the back, pelvis, ribs, and long bones
- An increased risk of bone fractures — sometimes even spontaneously, without trauma
- Possible compression of nerves by collapsed vertebrae, which can cause radiating pain in the arms or legs
**Kidney problems**
The abnormal proteins that plasma cell tumors produce can be filtered by the kidneys and cause damage there. This leads to:
- High blood pressure
- Fatigue and shortness of breath (from anemia and fluid buildup)
- Swollen ankles and feet
- In severe cases: kidney failure requiring dialysis
**Anemia and related symptoms**
The abnormal cells crowd out healthy blood cell production in the bone marrow:
- Severe fatigue and lack of energy
- Shortness of breath, even with light exertion
- Pallor
- Headaches and dizziness
**Infections**
Because the abnormal cells suppress the immune system, infections occur more frequently:
- Pneumonia
- Urinary tract infections
- Infections that persist longer and are harder to treat
**Neurological symptoms**
In some cases, abnormal proteins can deposit around nerves:
- Tingling and numbness in hands and feet
- Tingling that can gradually spread upward
**Hypercalcemia (too much calcium in the blood)**
Due to rapid breakdown of bone tissue, calcium can be released:
- Severe thirst
- Excessive urination
- Confusion and concentration problems
- Nausea and constipation (severe constipation)
**What this means for daily life: **
For many patients, this stage becomes overwhelming. The bone pain can be so severe that sitting and standing become difficult; sleep is problematic. Many people must adjust or stop their work. Shopping, housework and climbing stairs can become significantly burdensome. Infections require prompt medical care. The mental impact is considerable: a cancer diagnosis causes fear and uncertainty.
**Figures about this phase: **
The median survival (the point at which half of the patients unfortunately have passed away) for newly diagnosed myeloma has improved considerably over recent decades due to better treatments. With modern therapies, the median progression-free survival (how long one remains without disease growth) at the population level is somewhere between 4 and 7 years, depending on risk categories (2023-2025 data). These are population averages; individual disease progression varies greatly and depends on many factors: genetic characteristics of the tumor cells, response to treatment, age and other illnesses.
Phase 3: Treatment and response phase
Once myeloma is diagnosed, treatment begins. This phase can last months to years.
**Symptoms during treatment:**
Many of the symptoms described above (bone pain, fatigue, infections) can gradually improve as treatment takes effect. At the same time, side effects from medications may occur:
- Nausea, vomiting and loss of appetite
- Diarrhea or conversely constipation
- Mouth problems (ulcers, dry mouth)
- Peripheral neuropathy (tingling in feet and hands) — can sometimes be sensitive to certain medications and less so to others
- Fatigue from the treatment itself
- Increased risk of infection from medications that suppress the immune system
- Insomnia and anxiety
**Bone marrow and stem cell transplantation:**
Many patients undergo autologous hematopoietic stem cell transplantation (the use of their own stem cells). This brings additional symptoms:
- Severe fatigue and weakness
- Diarrhea
- Oral mucosa inflammation
- Higher infection risk (the immune system must recover)
- This usually lasts 2-4 weeks in the hospital
**What this means for daily life: **
For many patients, treatment is intensive. Regular hospital visits (weekly to monthly), blood tests and infusions structure the weeks. Many people cannot work and are heavily dependent on help from loved ones. Social contacts become limited (due to infection risks). Physically, many people are weak; even getting dressed can be tiring. Financial concerns arise (loss of income, expenses). Psychologically, this is a difficult period, with alternating between hope (if the disease responds) and fear (of side effects or insufficient effect).
**Figures about this phase: **
The response to first-line treatment (how well the tumor responds) has improved with newer drug combinations. Of patients with newly diagnosed myeloma, 80-95% achieve partial or complete remission (significant decrease in disease markers) — this depends on the specific medications and the risk profile. With first-line treatment, the median progression-free survival is approximately 4-7 years (depending on risk), but this shows great variation per patient. Progression-free survival has become longer since the introduction of proteasome inhibitors and immunomodulatory agents (2008-2020).
Phase 4: Remission and surveillance
After treatment, the disease can return to virtually undetectable levels. This is called "remission". This does not mean cure, but rather that the disease is under control.
**Symptoms in remission:**
In many cases, the severe symptoms of phase 2 disappear:
- Bone pain decreases or disappears
- Energy level improves
- Infection risks normalize
- Kidney values can improve
However, some side effects of treatment may persist:
- Peripheral neuropathy (tingling) may continue to exist
- Fatigue may remain present
- Bone demineralization can have noticeable consequences (risk of fractures)
**What this means for daily life: **
For many patients, this is a period of recovery. Many can return to work, sometimes in adapted form. Social contacts recover. Physically, many people feel much better, although full energy does not always return. Regular check-up visits (every 1-3 months) are necessary; blood tests and possibly imaging provide reassurance that the disease has not returned.
**Psychological aspect:**
However, this phase also brings uncertainty: patients live in anticipation of possible recurrence. Each check-up visit is approached with tension. For some, this is a moment to make future plans again; for others, fear remains prominent.
Phase 5: Relapse and refractory myeloma
Unfortunately, multiple myeloma returns in many patients — this is called "relapse" or "recurrence". This can happen months to years after remission. If the myeloma does not respond well to earlier treatment (or quickly returns), it is called "refractory" myeloma.
**Symptoms at recurrence:**
The symptoms from phase 2 usually return:
- Bone pain
- Kidney problems and high nitrogen levels
- Anemia with fatigue
- Infections
- Possibly new symptoms due to new tumor burden in other locations
**Treatment in this phase:**
There are different options, depending on what was used previously:
- Other drug combinations
- Bispecific antibodies
- Immunotherapy
- CAR-T cell therapy (genetically adapted own cells)
**What this means for daily life: **
This is mentally very stressful. Many patients had hoped for long-term control; the recurrence confronts them again with an uncertain future. Physically, the same limitations apply as in phase 2; depending on how much time has passed since remission, the body's recovery possibilities may be limited.
**Figures about this phase: **
Approximately 90% of patients with multiple myeloma experience relapse at some point. The median time to relapse after first-line treatment is 3-5 years in recent cohorts (2020-2025), but this varies enormously: some relapse within months, others only after 10+ years. With retreatment, the prognosis for a second or third remission is worse than the first; progression-free survival usually halves with each new line. These are population averages; some patients achieve long-term control after multiple treatments.
Phase 6: Advanced/refractory disease
After repeated relapses, the myeloma becomes harder to fight. Tumor cells develop resistance to medicines.
**Symptoms:**
- Severe bone pain, sometimes with bone fractures
- Severe anemia (fatigue, shortness of breath)
- Kidney failure
- Infections become more frequent and severe
- Neurological symptoms (tingling, confusion)