Multiple Myeloma: Signs, Symptoms, and New Treatments

Multiple Myeloma is a cancer of plasma cells that often hides in plain sight.

While it affects fewer people than many other cancers, it can quietly damage bones, kidneys, and the immune system before it’s discovered—making awareness and early detection essential.

What is Multiple Myeloma?

Multiple Myeloma (MM) starts in the bone marrow, where abnormal plasma cells crowd out healthy blood-forming cells and produce faulty antibodies (M-protein). These changes can weaken bones, lower blood counts, and impair kidney function. For a clear overview, see the National Cancer Institute’s myeloma guide.

Myeloma is most commonly diagnosed in people over 60, and risk is higher in Black/African American communities and in those with a history of MGUS or smoldering myeloma. The American Cancer Society estimates tens of thousands of new U.S. cases annually; find up-to-date statistics here.

Early signs and symptoms: what to watch for

Myeloma doesn’t always cause symptoms at first, which is why recognizing early clues can prevent lasting organ damage. Here are the early clues to watch for

and how to respond quickly if they appear.

Bone pain (often in the back, hips, or ribs), especially if persistent or worsening
Fatigue and weakness from anemia or systemic inflammation
Frequent infections, slow healing, or shingles flares
Unexplained weight loss or decreased appetite
Numbness/tingling in hands or feet (peripheral neuropathy)
Excessive thirst, constipation, or confusion (possible high calcium)
Swelling, foamy urine, or reduced urination (possible kidney stress)

Know the CRAB and SLiM-CRAB criteria

Doctors often use the CRAB criteria to flag organ damage from active myeloma:

Calcium elevated
Renal (kidney) dysfunction
Anemia
Bone lesions or fractures

The updated SLiM-CRAB adds biomarkers that predict imminent progression even before CRAB damage occurs: Sixty percent or more plasma cells in the marrow, involved/uninvolved free Light chain ratio ≥100 with involved light chain ≥100 mg/L, or ≥1 focal lesion on MRI. If these are present, treatment is usually recommended to prevent permanent harm.

When to see a doctor and which tests to ask about

If you have persistent bone pain, fatigue, recurrent infections, or any CRAB features, see your primary care clinician or a hematologist/oncologist. Tell them your full symptom timeline and ask whether myeloma screening labs are appropriate.

Blood tests: complete blood count (CBC); comprehensive metabolic panel (including calcium and creatinine); serum protein electrophoresis (SPEP), immunofixation (IFE), and free light chains.
Urine tests: 24-hour urine protein electrophoresis/IFE to detect Bence Jones protein.
Imaging: low-dose whole-body CT, whole-body MRI, or PET/CT to find lytic bone lesions.
Bone marrow evaluation: aspiration/biopsy for plasma cell percentage and genetic risk markers.

Learn more about how myeloma is diagnosed on Cancer.Net.

Treatment options: from monitoring to modern therapies

Myeloma care is personalized based on disease stage, genetic risk, symptoms, and your health goals. Treatment aims to control the cancer, prevent organ damage, relieve symptoms, and extend quality life. See an overview of evidence-based options in the NCI’s patient summary here.

Smoldering myeloma (no CRAB/SLiM-CRAB damage)

Active surveillance with labs and imaging is standard for most. A subset of high-risk smoldering cases may join clinical trials testing early therapy.

Newly diagnosed, transplant-eligible

Induction therapy: typically a 3–4 drug combination (e.g., an immunomodulator + proteasome inhibitor + steroid ± anti-CD38 antibody).
Autologous stem cell transplant (ASCT): consolidates response for fit patients.
Maintenance therapy: often lenalidomide-based to prolong remission.

Newly diagnosed, transplant-ineligible

Combination regimens adjusted for age and comorbidities, frequently including an anti-CD38 antibody up front.

Relapsed/refractory myeloma

Options include switching drug classes (proteasome inhibitors, IMiDs, anti-CD38 antibodies), targeted agents like selinexor, BCMA-directed therapies, and clinical trials.

Supportive care is crucial at every stage: bone-strengthening agents (bisphosphonates/denosumab), vaccines, antivirals, clot prevention when needed, pain control, and physical therapy. Read more on bone protection here and supportive care tips from the International Myeloma Foundation.

New FDA-approved therapies changing the landscape

Over the last few years, the FDA has cleared several transformative therapies for relapsed/refractory Multiple Myeloma, many targeting the BCMA or GPRC5D proteins on myeloma cells. You can scan an updated list of approved drugs here. Highlights include:

Teclistamab-cqyv (Tecvayli): the first bispecific antibody for myeloma (BCMA×CD3), approved in 2022 for previously treated patients. It redirects T cells to attack myeloma cells. See the FDA announcement here.
Talquetamab-tgvs (Talvey): a bispecific antibody targeting GPRC5D×CD3 for heavily pretreated disease (2023). Learn more from the FDA approval notice.
Elranatamab-bcmm (Elrexfio): a BCMA×CD3 bispecific for relapsed/refractory cases (2023). See details in the FDA summary here.
Ciltacabtagene autoleucel (Carvykti): a BCMA-directed CAR T-cell therapy first approved in 2022 and expanded to earlier lines in 2024. Read the NCI update here.
Idecabtagene vicleucel (Abecma): another BCMA-directed CAR T-cell therapy with expanded 2024 indications for earlier treatment settings. NCI overview here.

These innovations bring high response rates for some patients who’ve exhausted other options. That said, they require specialized centers and careful monitoring for side effects such as cytokine release syndrome (CRS) and immune-related neurological symptoms. Learn about immunotherapy side effects here and how CAR T-cell therapy works here.

Why early detection matters

Starting treatment before irreversible damage occurs improves outcomes. Identifying SLiM-CRAB features, stabilizing bones and kidneys early, and tailoring therapy using genetic risk markers all increase the chances of a deep, durable response. Population screening isn’t recommended, but monitoring people with MGUS or smoldering myeloma—and promptly evaluating new symptoms—can prevent fractures, kidney failure, and hospitalizations.

Practical steps you can take today

Listen to your body: Persistent bone pain, fatigue, infections, or any CRAB red flags warrant evaluation.
Bring a checklist to your appointment: ask about CBC, calcium/creatinine, SPEP/IFE, free light chains, urine testing, and appropriate imaging.
Ask about risk and goals: genetic risk profiling, transplant eligibility, and lifestyle factors (bone safety, fall prevention, nutrition, and exercise).
Plan supportive care: bone-strengthening therapy, vaccines, antiviral prophylaxis if needed, and symptom management.
Consider a clinical trial if you’re newly diagnosed or relapsing—search open studies via the NCI trial finder.

Trusted resources

If you’re concerned about symptoms, don’t wait—schedule an appointment with your clinician and bring this article as a discussion guide. Acting early can make a meaningful difference.