Multiple Myeloma: Diagnosis and Next Steps

Hearing the words “multiple myeloma” can feel like someone just switched your life’s playlist to
a mystery soundtrack. The good news: this cancer is better understood and more treatable today
than ever before. Knowing how myeloma is diagnosed and what happens next can turn some of that
fear into a practical game plan you can walk through with your care team.

In this guide, we’ll break down how doctors figure out what’s going on, what all those blood and
bone marrow tests really mean, how staging works, and what treatment and life after diagnosis
typically look like. We’ll keep the tone human (with a hint of humor), but the content grounded
in solid medical information.

What Is Multiple Myeloma, Exactly?

Multiple myeloma is a cancer of plasma cells, a type of white blood cell that normally lives in
your bone marrow and helps you fight infections by making antibodies. In myeloma, these plasma
cells turn cancerous, grow out of control, and crowd out healthy blood-forming cells.

These abnormal plasma cells often make large amounts of a single, useless antibody fragment
called M protein or a “monoclonal protein.” This protein can show up in your
blood, your urine, or both. Over time, myeloma can damage bones, kidneys, the immune system, and
the blood counts your body relies on.

You’ll sometimes hear related terms:

MGUS (Monoclonal Gammopathy of Undetermined Significance) – An early, non-cancer
condition where M protein is present but there’s no organ damage and very few abnormal plasma cells.
Smoldering multiple myeloma – A middle stage with more abnormal plasma cells and
higher M protein, but still no symptoms or organ damage.
Active multiple myeloma – The “real deal” cancer that causes symptoms and organ
damage and requires treatment.

The diagnosis process is all about answering two big questions:
“Is this myeloma?” and “If so, is it active and needing treatment right now?”

How Doctors Diagnose Multiple Myeloma

Step 1: Symptoms, Story, and Physical Exam

Many people end up being evaluated for myeloma after noticing things like:

Bone pain (especially in the back, hips, or ribs)
Unexplained fatigue or weakness
Frequent infections
Nausea, constipation, or confusion from high calcium levels
Unintentional weight loss

Others are caught completely off guard: routine blood work shows anemia, kidney problems, or
high protein levels, and the doctor starts digging deeper.

A physical exam can’t diagnose multiple myeloma by itself, but it helps your provider look for
things like bone tenderness, weakness, neurological changes, and signs of anemia or infection.

Step 2: Blood Tests

Blood testing is where myeloma really starts to show its fingerprints. Your team may order:

Complete blood count (CBC) – Looks for low red blood cells (anemia), low
white cells, or low platelets.
Comprehensive metabolic panel – Checks kidney function and calcium levels.
High calcium and abnormal creatinine can point toward organ damage from myeloma.
Serum protein electrophoresis (SPEP) and immunofixation – These tests detect
and characterize M protein in the blood.
Serum free light chain (FLC) assay – Measures light chains (antibody pieces)
in the blood and the ratio between them; a severely skewed ratio can signal active myeloma.
Beta-2 microglobulin (B2M), albumin, LDH – These markers help with staging and
prognosis. Higher B2M and LDH or low albumin often mean more aggressive disease.

Think of these blood tests as the “satellite view” of what’s going on in your bone marrow and
organs. They tell your team if more invasive testing is needed and help guide what comes next.

Step 3: Urine Tests

Urine testing looks for light chains (also known as Bence Jones proteins) that are being filtered
by the kidneys. You may be asked for:

24-hour urine collection to measure how much protein is actually being lost
over a full day.
Urine protein electrophoresis and immunofixation to identify monoclonal
proteins in the urine.

These tests give clues about both myeloma activity and kidney health, which is important for
treatment planning.

Step 4: Bone Marrow Biopsy and Cytogenetics

A bone marrow biopsy is usually the “make it official” step in diagnosing multiple myeloma. A
needle is used to take a small sample of bone marrow, typically from the back of the hip bone.
You’ll get numbing medicine and sometimes sedation to help you stay comfortable.

In the lab, specialists look for:

Percentage of plasma cells – At least 10% clonal (abnormal) plasma cells in the
marrow, plus other criteria, strongly supports a myeloma diagnosis.
Genetic changes in the myeloma cells – Testing such as FISH (fluorescence in
situ hybridization) looks for changes like deletion 17p or certain chromosome translocations.
These don’t cause symptoms directly but help determine risk and guide treatment intensity.

Modern diagnostic criteria also recognize that even before classic organ damage shows up,
certain “biomarkers of malignancy” are enough to start treatment. These include:

60% or more clonal plasma cells in the bone marrow
A very abnormal free light chain ratio
More than one focal lesion on MRI scans of the bones

Why does this matter? It means your team can act earlier to prevent serious bone or kidney damage
instead of waiting for a crisis.

Step 5: Imaging Tests and the CRAB Features

Imaging tests look at your skeleton and sometimes other organs to see where myeloma may be
causing damage. Common studies include:

Whole-body low-dose CT or skeletal survey – To look for bone lesions or
fractures.
MRI – Useful for spine, pelvis, and areas where nerve compression or subtle
marrow involvement is suspected.
PET/CT scan – Helps show areas of active disease, especially when standard
X-rays aren’t giving the full picture.

You may hear your care team talk about CRAB features that indicate organ damage
caused by myeloma:

C – Elevated Calcium
R – Renal (kidney) problems
A – Anemia
B – Bone lesions or fractures

If you have myeloma cells in the marrow plus CRAB features or certain biomarkers, that’s usually
enough to diagnose active multiple myeloma and move on to treatment planning.

Staging and Risk: Making Sense of the Numbers

Once myeloma is confirmed, your team will stage it using systems such as the
Revised International Staging System (R-ISS). Instead of focusing on tumor size
(like some cancers), the R-ISS uses blood test markers and genetic features to estimate how
aggressive the disease is.

Factors include:

Beta-2 microglobulin level
Albumin level
LDH (lactate dehydrogenase)
Specific high-risk genetic abnormalities in the myeloma cells

These results place myeloma into stages (I, II, or III) and risk categories (standard vs high
risk). Higher stages and high-risk genetics generally mean the disease is more aggressive and may
need stronger or more complex treatment, but they do not predict exactly how you will do
as an individual. People surprise statistics all the time.

First Treatment Decisions: What Happens After Diagnosis

Diagnosing multiple myeloma is step one. Next, your team looks at:

Your age and overall health
Kidney function and bone health
Myeloma stage and risk level
Your personal preferences and priorities

Treatment is usually led by a hematologist-oncologist and often involves several types of
therapy used in a sequence or a long-term plan.

If You’re Eligible for a Stem Cell Transplant

For many people who are relatively younger and medically fit, the standard path looks like:

Induction therapy – A combination of drugs (often 3 or 4) to reduce the
number of myeloma cells. Common regimens may include a proteasome inhibitor, an
immunomodulatory drug, a steroid, and often a monoclonal antibody.
Autologous stem cell transplant (ASCT) – Your own blood stem cells are
collected, you receive high-dose chemotherapy to wipe out myeloma cells, and then your stem
cells are infused back to rebuild the bone marrow.
Maintenance therapy – A lower-intensity, usually long-term treatment (often a
pill) to help keep myeloma controlled and delay relapse.

Not everyone chooses transplant, and not everyone needs it right away. But for many eligible
patients, it remains a key part of long-term disease control.

If You’re Not a Transplant Candidate

If age, other medical conditions, or personal preference make transplant less suitable, you still
have strong options. Treatment often includes:

Combination drug therapy with two, three, or sometimes four agents tailored
to your fitness and health.
Continuous or long-term therapy with dose adjustments based on side effects
and response.
Maintenance or consolidation treatment once the disease is under good control.

The goal is the same: get the disease into the deepest possible response with a treatment plan
you can realistically tolerate and stick with.

Other Important Parts of Myeloma Care

Treating myeloma isn’t only about killing cancer cells. Supportive care is just as critical:

Bone-strengthening medications like bisphosphonates or denosumab to reduce
fractures and bone pain.
Pain control, which may include medications, physical therapy, or targeted
radiation to painful lesions.
Infection prevention – Vaccinations, close monitoring, and sometimes
preventive antibiotics or antivirals.
Newer immunotherapies (like CAR T-cell therapy or bispecific antibodies),
usually used after other treatments, can provide powerful options at relapse in specialized
centers.
Clinical trials, which can offer access to cutting-edge therapies while
contributing to better care for future patients.

Your care plan will be highly personalized. Two people with the same diagnosis can have very
different treatment journeys based on their unique situation.

Follow-Up Care and Living with Multiple Myeloma

Multiple myeloma is typically considered a chronic, relapsing disease. That means ongoing
follow-up is part of the long game, even during times when you feel well and the cancer is quiet.

Follow-up usually includes:

Regular blood tests to track M protein, light chains, kidney function, and blood counts
Periodic urine tests, especially if you had light-chain disease
Imaging when there’s concern for new bone pain or relapse
Visits with your oncology team to check symptoms, side effects, and quality of life

Beyond labs and scans, survivorship care also focuses on:

Bone health – Managing calcium and vitamin D, weight-bearing exercise if
safe, and fall prevention.
Heart and kidney protection – Choosing and adjusting medicines carefully.
Mood and mental health – Anxiety and depression are common and absolutely
worth addressing with counseling, support groups, or medication when needed.
Fatigue management – Energy-saving strategies, gentle activity, and sleep
hygiene can all help.

It’s a lot, but you don’t have to manage it solo. Think of your care team as your long-term pit
crew, not just your emergency response unit.

Practical Questions to Ask Your Care Team

When you’re newly diagnosed, it helps to show up to appointments with a short list of questions.
Here are some to consider:

“Is my myeloma considered standard-risk or high-risk?”
“What stage is my myeloma, and what does that realistically mean for me?”
“What treatment plan do you recommend first, and what’s our plan B if it doesn’t work?”
“Am I a candidate for a stem cell transplant, now or in the future?”
“What side effects should I watch for, and who do I call if they show up?”
“How often will I need blood tests and scans?”
“Are there clinical trials I should know about?”
“What lifestyle changes can help me stay as strong as possible?”

Take notes, bring a friend or family member if you can, and don’t be shy about asking the same
question more than once. This is your body and your lifeclarity is not optional.

Real-Life Experiences: Navigating Diagnosis and Next Steps

Everyone’s multiple myeloma story is different, but some themes show up again and again when
people talk about their experiences. While the details below are based on many patients’ journeys
rather than one specific person, they reflect real-world patterns many people recognize.

One common thread is how random the diagnosis can feel. Someone goes in for a
check-up because they’re tired, assumes they just need more sleep, and then suddenly the labs
come back with anemia and high protein levels. Another person tweaks their back picking up
groceries, gets an X-ray, and learns they have bone lesions. It’s not dramatic like a movie; it’s
more like your life takes a sharp left turn during an ordinary Tuesday.

After the initial shock, the next phase is usually an intense whirl of appointments: hematology,
imaging, biopsies, blood draws, and what feels like an entire alphabet of test names. Many people
describe this as the “information firehose” stageterrifying and exhausting, but also strangely
reassuring. You learn that there’s an organized plan: rule things in, rule things out, and build a
treatment strategy customized to you.

Emotionally, it’s common to bounce between:

Fear and uncertainty – Worrying about the future, your family, your work, and
what treatment will feel like.
Relief – Finally having an explanation for months (or years) of fatigue, pain,
or infections.
Determination – A sense of, “Okay, this is real. What’s the plan and how do we
attack this?”

On a practical level, people often talk about how important it is to organize
information early. That might mean keeping a notebook or digital file with:

Test dates and results
Medication lists and doses
Questions for upcoming visits
Names and contact details for your care team

It sounds simple, but when you’re tired or stressed, having everything written down saves energy
and helps you feel more in control.

Support systems matter, too. Some people lean on family or close friends; others find comfort in
support groupseither in person or onlinewhere they can connect with people who “get it”
without a lot of explanation. It’s totally normal to want privacy at first and slowly open up as
you find your footing.

Many patients also describe adjusting their definition of “normal.” Maybe “normal” used to mean
working a full-time job, going to the gym, and doing all the errands on your list. After a myeloma
diagnosis and treatment, “normal” might become:

Working fewer hours or changing roles
Prioritizing sleep and rest days without guilt
Saying “no” more often to protect your energy
Building movement into your day in gentler ways, like walking or stretching

Over time, people often describe a shift from feeling like myeloma has completely taken over
their identity to seeing it as part of their life storynot the whole thing. They still
make plans, travel, celebrate milestones, and laugh (a lot). Medical appointments become part of
the rhythm of life, like an extra, very serious hobby you never asked for but have become
unexpectedly skilled at managing.

The takeaway? While multiple myeloma is a serious diagnosis, many people learn to live
meaningfully with it. A combination of modern treatments, proactive follow-up, emotional support,
and everyday coping strategies can help you move from shock and uncertainty toward a new,
workable version of “next.”

Conclusion: Turning a Scary Diagnosis into a Clear Plan

“Multiple myeloma” is a big, intimidating phrase, but understanding the stepsdiagnosis, staging,
treatment options, and follow-upcan make it feel far less mysterious. Lab tests, imaging, and
bone marrow biopsies aren’t just random hurdles; together they form a detailed map that helps
your care team target the disease as precisely as possible.

Your next steps usually include building a treatment plan with your hematologist-oncologist,
learning what to expect from therapies, and setting up regular follow-up appointments. Along the
way, it’s completely okay (and encouraged) to ask questions, get second opinions, and seek
emotional and practical support.

This article is for education and empowerment, not a personalized medical plan. Always discuss
your specific test results, treatment options, and concerns with your healthcare teamthey know
your case best and can help turn all this information into a plan that fits your life.