Multiple myeloma relapse

This page was reviewed under our medical and editorial policy by

Michael Rosenzweig, MD, MS, Hematologist-Oncologist, City of Hope | Duarte

This page was reviewed on June 5, 2023.

Multiple myeloma is a treatable but currently incurable illness. When multiple myeloma reappears after successful treatment, it’s called a relapse. Despite improvements in care and novel therapies for the treatment of multiple myeloma, nearly all patients experience relapse.

After the initial treatment for multiple myeloma, called first-line or frontline therapy, follow-up care is essential. Maintenance therapy to reduce the risk of relapse, and catching relapse early, are the first steps to managing the disease. In checkups every one to three months, blood and urine tests, bone marrow evaluations and other imaging scans may be performed to check for signs of relapse.

Some patients may have scans that show no evidence of disease for up to three years or more, according to the International Myeloma Foundation. A study published in Leukemia in 2016 examined 511 patients and found the median time to relapse was 26.9 months after completing first-line therapy. With new treatment approaches, the time to relapse is increasing.

When multiple myeloma relapses, new tests will be taken and care plans will be updated to help control the cancer.

Different terms may be used to describe a relapse:

Progressive disease: Disease that progresses by serum or urine laboratory tests or by imaging studies.

Refractory disease: Disease that becomes non-responsive or progressive on therapy or within 60 days of the last treatment.

Primary refractory: Disease that fails to respond adequately to initial treatment without evidence of progression.

Relapse is different from being diagnosed with a second type of cancer. It’s important to note that multiple myeloma patients have an increased risk for developing two other types of blood cancers: acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Patients will be monitored for both relapse and the occurrence of new cancers during their follow-up care.

Relapsed multiple myeloma symptoms

Regular physical exams, tests and symptom check-ins are part of follow-up care for multiple myeloma treatment.

Relapses may be symptomatic, meaning patients notice signs and symptoms. Or relapses may be biochemical, meaning doctors detect certain abnormalities in blood tests, urine tests or other exams, even though patients may experience no symptoms.

Symptoms of relapse may be similar to the initial onset of multiple myeloma, different or nonexistent. Symptoms may include:

  • Bone pain, often in the skull, hips or back
  • Weakness in bones, limbs or muscles
  • Broken bones, especially when a bone breaks from only minor injury
  • Shortness of breath
  • Fatigue, typically caused by anemia (low red blood cell counts)
  • Easily bruised skin or serious bleeding
  • Extreme thirst, drowsiness, vomiting or constipation, resulting from hypercalcemia (elevated calcium levels)
  • Frequent infections or fevers, a result of multiple myeloma weakening the immune system

Relapsed multiple myeloma treatment

Treatment for relapsed multiple myeloma depends on a variety of factors, such as:

  • How many times the cancer has relapsed
  • How long it has been in remission
  • How well previous treatments have worked
  • Current health

A number of tests will be done to analyze the relapsed cancer and update the care plan, tailored to each patient.

Depending on the specific disease history and presentation at the time of relapse, different treatment plans may be recommended:

Watchful waiting: For a slow-progressing, stable disease, patients and their doctors might decide to withhold treatment until the cancer worsens.

Same treatment: If the period to relapse was long (more than six months), the first choice for relapsed myeloma may be to use the same therapies that worked the first time.

Stem cell transplant: For patients with a long-lasting remission (two to three years) after an autologous stem cell transplant, a second stem cell transplant may be helpful.

Combination therapies: Refractory multiple myeloma is almost always treated with a different therapy combination than used before. For subsequent relapses, different combination therapies or clinical trials may be used. A wide variety of options are available to treat multiple myeloma if it becomes unresponsive to therapies that worked for the first few relapse periods.

As with any cancer treatment, treatment for multiple myeloma may cause temporary or even permanent side effects. Certain medications might be used during and after care to reduce discomfort caused by side effects and help patients live as normal a life as possible.

For many patients, multiple myeloma will cycle through periods of relapse and no evidence of disease (remission). As the disease progresses, the remission periods typically become shorter and the disease more difficult to treat.

Early relapse treatment

Early relapse occurs if the multiple myeloma is resistant to first-line therapies or has certain mutations that make the cancer high-risk of early progression.

Each case of multiple myeloma is highly individual, and patients may need to try different combinations and dosages of drug therapies to figure out which is most effective. Typically, early-relapse care includes some combination of drugs from four classes:

  • Proteasome inhibitors (PIs), which may kill or stop cancer cells from growing by preventing the breakdown of proteins inside cells
  • Immunomodulatory drugs (IMiDs), which help the immune system attack the cancer
  • Monoclonal antibodies (mAbs), which are proteins that specifically attach to multiple myeloma cells to target them for destruction
  • Steroids, which enhance the effectiveness of nearly all combination therapies

Refractory relapse treatment

Relapsed multiple myeloma might behave differently from the initial disease. During each round of treatment, the goal is to kill abnormal cells. When almost all the cancer cells are destroyed, patients may undergo tests that show no evidence of disease. If a small, undetectable amount of cells that were resistant to the applied treatment survive, they may continue to grow until the multiple myeloma becomes detectable again. Because it grew from treatment-resistant cells, this relapsed multiple myeloma will require new therapies.

If relapsed myeloma is resistant to one or more previous therapies, other treatment options may be used, including:

  • Use of the previous therapies for relapse occurring after six months
  • A different combination of therapies for relapse occurring before six months
  • Autologous stem cell transplant
  • Immune effector cell therapy including CAR T-cells
  • Bispecific antibody treatment
  • Clinical trials with novel therapies

In general, triplet combination therapies (using three drugs) are recommended for RRMM, because they are more effective than using just one or two medications at a time.

Clinical trials

Clinical trials are an option for multiple myeloma that is unresponsive to conventional treatment. A clinical trial is a research study of a new drug or novel therapy intended to improve cancer treatment. Patients may join a clinical trial at any time before, during or after treatment.


Modern therapies have transformed multiple myeloma from a fatal disease to a chronic, manageable condition for many, but not all, patients. The National Cancer Institute (NCI) collects data on the survival rates of all cancers from the onset of diagnosis. Based on 2012 to 2018 NCI data, the percentage of patients expected to survive five years after initial diagnosis of myeloma is 57.9 percent. About 31.6 percent of patients may be expected to survive 10 years after diagnosis, according to 2000 to 2018 NCI data.

In general, the longer the periods that patients undergo scans that show no evidence of disease, the better the prognosis. Shorter periods of no evidence of disease and early relapse are associated with a worse prognosis.

It may be stressful to worry about cancer coming back during remission periods. While there’s no sure way to lower the risk of relapse, maintaining a healthy weight, abstaining from smoking, getting regular physical exercise and eating a well-rounded diet may benefit patients’ general health.

Support communities may also be empowering for patients and caregivers of those with multiple myeloma. The Cancer Fighters online community connects patients with peers who are also undergoing multiple myeloma treatment, while also providing resources and new information.

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