Multiple Myeloma: Staging and Treatment

What is staging for cancer?

Staging looks at how much cancer is in your body and where it is. Tests like blood work (CBC, or complete blood count), urine tests, biopsy, X-ray, CT, and bone marrow biopsy may be done to help stage your cancer. Your providers need to know about your cancer and your health so that they can plan the best treatment for you.

Multiple myeloma (MM) is staged using the Revised International Staging System (RISS) based on:

• How much albumin, beta-2-microglobulin, and LDH is in the blood.
• Certain gene changes (cytogenetics) of the cancer.

How is multiple myeloma staged?

Using the results of blood tests, urine tests, biopsies, and imaging tests, your myeloma will be given a stage. This will help guide your treatments. Below is a summary of the staging system. Talk to your provider about the stage of your cancer.

• RISS Stage Group I: Serum beta-2 microglobulin is less than 3.5 (mg/L), albumin level is 3.5 (g/dL) or greater, cytogenetics are considered “not high-risk” (meaning there are not certain changes to chromosomes 17, 4, 14, or 16), and LDH levels are normal.
• RISS Stage Group II: Not stage I or III.
• RISS Stage Group III: Serum beta-2 microglobulin is 5.5 (mg/L) or greater, cytogenetics are considered “high-risk” (meaning there is at least one kind of change to chromosomes 17, 4, 14, or 16), and LDH levels are high.

How is multiple myeloma treated?

Treatment for multiple myeloma is based on many things, like your cancer stage, age, overall health, and test results.

Treatment also depends on which type of MM you are diagnosed with. The types are listed here:

• Smoldering multiple myeloma: This is an early form of MM. There will be no symptoms yet (asymptomatic). For the most part, your blood counts, kidney function, calcium levels, and bones/organs will be normal, but you may have other signs of myeloma in your body, such as:
  • Too many plasma cells in your bone marrow.
  • A high level of monoclonal immunoglobulin in your blood.
  • A high level of light chains (also called Bence Jones protein) in your urine.
• Active multiple myeloma: This form of MM will cause symptoms. These may include:
  • Bone problems (pain, weakness, broken bones).
  • Low blood counts (low red blood cells/anemia, low white blood cells/leukopenia, low platelets/thrombocytopenia).
  • High levels of calcium in the blood.
  • Changes to your nervous system, like numbness, weakness, and tingling. If you have sudden back pain, numbness in your legs, or muscle weakness, call 911 or go to the Emergency Room right away. These are signs of a serious problem called spinal cord compression.
  • Thickened blood in your body, which can cause confusion and symptoms of a stroke. Call your provider right away if you have these symptoms.
  • Kidney problems.
  • Infections.

Studies have helped us find out more about treating myeloma. Most patients do well with initial therapy and can live with myeloma as a chronic cancer for many years. Your treatment for active myeloma may include some or all of these:

• Chemotherapy and other medications.
• Stem Cell Transplant.
• CAR T-Cell Therapy.
• Radiation Therapy.
• Supportive Treatments.
• Clinical Trials.

Patients with smoldering (asymptomatic) myeloma (stage I) should be followed closely, without treatment. Research studies have found that treating asymptomatic myeloma does not improve long-term survival.

Chemotherapy and Other Medications

Chemotherapy is a type of medication that goes throughout your whole body to kill cancer cells. The ones used to treat multiple myeloma are cyclophosphamide, etoposide, doxorubicin, liposomal doxorubicin, melphalan, and bendamustine. Often, one of these drugs is given with another type of drug (like corticosteroids and immuno-modulating medication). Corticosteroids include dexamethasone and prednisone. An immune-modulating medication is one that changes your immune response to fight the cancer cells. Immuno-modulating medications include thalidomide, lenalidomide, and pomalidomide.

Other kinds of medication that can be used to treat MM include proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib. Medications called monoclonal antibodies can also be used, including daratumumab, daratumumab and hyaluronidase, isatuximab, and elotuzumab. Belantamab mafodotin-blmf is an antibody-drug conjugate, meaning a monoclonal antibody is attached to a chemotherapy drug.

Your provider will likely combine some medications to treat your MM, which is often called a regimen.

High-Dose Chemotherapy with Stem Cell Transplant

High-dose chemotherapy and autologous stem cell transplant (using your own stem cells) can be used in some cases. This may be used as the first-line therapy or after the myeloma has progressed while on other therapies. Having a transplant may not be the right treatment for patients who are older (over 65), if they have other health issues, or some DNA abnormalities.  

There are three phases of stem cell transplant therapy:

• Induction therapy: Induction chemotherapy is the chemotherapy regimen you are given to kill as many myeloma cells as possible without hurting the stem cells. You are given several cycles of chemotherapy that often include bortezomib with dexamethasone and another agent (or agents) that may include thalidomide, carfilzomib, ixazomib, lenalidomide, doxorubicin, daratumumab, cisplatin, etoposide and/or cyclophosphamide. Your providers will talk with you about your specific regimen of medications.
• Stem cell transplant: After induction therapy, your stem cells will start to be collected so that they can be given back to you later. Stem cells can be taken from your blood instead of right from your bone marrow. The next part of the transplant is often done in the hospital. You will be given high doses of chemotherapy to kill as much of the myeloma as possible. This round of chemotherapy aims to also damage or kill the stem cells in your body. A day or two after this chemotherapy, your previously collected stem cells are thawed and given back to you through a catheter. These cells replace the stem cells that were damaged during the high-dose chemotherapy, letting your body recover from this chemotherapy. 
• Maintenance therapy: After transplant, if you go into remission, you may or may not need treatment with "maintenance" chemotherapy. Your care team may choose to watch you closely (also called observation) instead. This is often a less intense chemotherapy regimen and its goal is to put you in remission for longer. Maintenance therapy may include lenalidomide, ixazomib, or bortezomib. These medications may be used alone or in combination.

Some studies are looking at the benefit of a second transplant (called tandem transplant) for patients who do not reach full remission after the first transplant. With this therapy, a second transplant is done within six months of the first. Up to half of the patients treated with tandem transplants may have a complete response, but this is still being studied. The use of an allogeneic transplant, one in which cells from a donor are used, is also being studied.

CAR T-Cell Therapy

Chimeric antigen receptor (CAR) T-cell therapy is a type of targeted therapy that helps your body use its own immune system to fight cancer cells. Immune cells, called T cells, are taken from your blood (called leukapheresis). These removed T cells are frozen, sent to a lab, and genetically changed to have certain receptors on their surface. These receptors help your T cells find and attach to proteins on the cancer cells. The lab will make many of these T cells. When these T cells are ready, you will receive chemotherapy to kill some of the cancer. The CAR T-cells are then given back to you through your blood. These T cells find remaining cancer cells, attach to them, and start to attack them.  Idecabtagene vicleucel and ciltacabtagene autoleucel are CAR T-cell therapies that target the BCMA protein that is found on myeloma cells.

Relapse

Many patients who have been treated for MM relapse at some point. This means that the MM has come back. Treatment for relapse depends on the treatment you have already had, how long you were in remission (cancer free), any side effects of treatments, and other health issues. Most often chemotherapy or immunotherapy medication is used.

Radiation Therapy

Radiation therapy is the use of high energy x-rays to kill cancer cells. It can be used to treat a plasmacytoma which is a solid tumor made of myeloma cells. It can also be used to treat patients who have bone pain caused by myeloma may be treated with low-dose radiation. Your radiation oncologist will be able to talk to you about if radiation can be used as part of your treatment plan.

Supportive Treatments

Often, the treatment for multiple myeloma includes supportive treatments. These treatments don’t treat the cancer, but the other health issues being caused by the cancer. These can include:

• Patients who have kidney failure when diagnosed with MM need treatment quickly to improve the chances of kidney function getting better. Both bortezomib and lenalidomide have been found to help reverse kidney damage.
• When there are signs and symptoms of spinal cord compression, dexamethasone should be started right away, followed by urgent imaging of the spine. A neurosurgeon and/or radiation oncologist should be consulted to consider surgical decompression of the spine or radiation therapy to the spine.
• Bisphosphonates are commonly used in patients with myeloma to strengthen bones, prevent fractures, and lower calcium levels. Bisphosphonates (pamidronate, zoledronate) stop bone breakdown and help form new bone. Long-term use of bisphosphonates is linked to a small risk of osteonecrosis of the jaw (death of the jaw bone), atrial fibrillation, unusual fractures, and esophageal cancer. You should have a baseline dental exam before starting bisphosphonate therapy. Often, the benefits of bisphosphonates outweigh the risks, but it is important to talk about the risks and benefits with your care team. Another treatment for bone disease is the use of denosumab.

Talk to your care team about any questions you may have about your treatment for multiple myeloma.

Clinical Trials

You may be offered a clinical trial as part of your treatment plan. To find out more about current clinical trials, visit the OncoLink Clinical Trials Matching Services.

Making Treatment Decisions

Your care team will make sure you are included in choosing your treatment plan. This can be overwhelming as you may be given a few options to choose from. It feels like an emergency, but you can take a few weeks to meet with different providers and think about your options and what is best for you. This is a personal decision. Friends and family can help you talk through the options and the pros and cons of each, but they cannot make the decision for you. You need to be comfortable with your decision – this will help you move on to the next steps. If you ever have any questions or concerns, be sure to call your team.