Multiple Myeloma

Treatment

The goal of treating multiple myeloma is to reach remission, which means no longer having any signs or symptoms of the disease.

Doctors are now able to tailor treatments for each patient to maximize effectiveness and minimize potential side effects. Multiple myeloma is often treated as a chronic condition that has multiple relapses, and many people are able to manage this disease and lead healthy, active lives.

Your doctor will likely recommend one or more of the following therapies depending on the stage of the disease and your age, overall health, symptoms, previous treatments and preference.

Following are the types of available treatment options.

Watchful waiting may be recommended for people with monoclonal gammopathy of unknown significance (MGUS), smoldering myeloma or early-stage disease who do not have symptoms. Monitoring these conditions and waiting to begin treatment offer people the possibility of avoiding the side effects of treatment as long as possible and hopefully without affecting the outcome. Research is ongoing to determine if patients with smoldering myeloma may benefit from early treatment.

During watchful waiting, it is important to make and keep regular checkups to look for signs and symptoms because treatment should begin as soon as the disease progresses or symptoms appear.

Chemotherapy is a common treatment option for multiple myeloma. Most people receive some form of it, which may consist of a single drug or multiple drugs given in combination. It may also be combined with other types of treatment.

Usually given in cycles that consist of a treatment period followed by a break to allow healthy cells to recover, chemotherapy may be given orally or be injected intravenously (IV) (see Figure 2). Many oral drugs may be taken at home, and IV drugs are given in a doctor’s office, clinic or hospital.

Corticosteroids are myeloma cell-fighting drugs that are used to treat multiple myeloma and ease the side effects of chemotherapy, particularly nausea and vomiting. Given orally or in injection form, these drugs can be used alone or in combination with chemotherapy. Corticosteroids also help reduce inflammation and may offer other benefits.

Stem cell transplantation may be used. An autologous transplant involves using the patient’s own stem cells, which are collected, filtered, processed and frozen. High-dose chemotherapy and sometimes full-body radiation (conditioning) are given to destroy the cancer cells. Thawed cells are infused back into the patient’s body.

An allogeneic transplant may be used for patients with a high risk of relapse, those who aren’t responding fully to other treatments or those who have relapsed disease. It uses stem cells donated by a family member (a sibling has a 1 in 4 chance of being a donor match) or an unrelated donor through a national or international registry (See Stem Cell Transplantation).

Targeted therapy is used to slow the progression of disease. Targeted therapy drugs may be given orally or intravenously (IV) and travel throughout the body via the bloodstream looking for specific proteins and tissue environments of myeloma cells to block the growth and spread of cancer.

Types of targeted therapy to treat multiple myeloma include proteasome inhibitors, histone deacetylase (HDAC) inhibitors, angiogenesis inhibitors, immunomodulators and a first-in-class oral selective inhibitor of nuclear export (SINE). Proteasome inhibitors target enzymes in proteasomes that digest proteins in cells, helping to slow or stop myeloma cell growth and development. HDAC inhibitors interact with histones (proteins in chromosomes) to affect the gene expression inside myeloma cells. Angiogenesis inhibitors work by blocking the growth of new blood vessels that feed myeloma cells. Immunomodulators are used to treat multiple myeloma by helping the immune system find and attack myeloma cells. These drugs can be effective in treating newly diagnosed multiple myeloma and relapsed or refractory disease.

SINEs block the export of tumor suppressor, anti-inflammatory and growth regulatory proteins, leading to an accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell.

Immunotherapy is a treatment that works with or stimulates a person’s own immune system to recognize and destroy cancer cells (see Figure 1). Because myeloma cells are developed from mutated healthy cells in the body, the immune system may have difficulty recognizing myeloma cells as foreign. Training the immune system to respond to cancer has the potential for a more lasting response that can extend beyond the end of treatment. Immunotherapy may be given intravenously (IV).

Monoclonal antibodies (mAbs) are another type of immunotherapy drug used to treat multiple myeloma. Antibodies (proteins) are made by the immune system to help fight infection. Laboratory-made mAbs are designed to attack a specific target, such as proteins, found on myeloma cells.

Clinical trials involving other types of immunotherapy may also be considerations. Ask your doctor if immunotherapy is a treatment option for you.

Radiation therapy destroys cancer cells and shrinks tumors using high doses of radiation. External-beam radiation therapy (EBRT) is the most commonly used type (see Figure 3). Some people with localized myeloma or bone pain that does not lessen with chemotherapy may receive radiation therapy to specific parts of the body for pain relief.

Surgery may be used to treat a plasma-cytoma (malignant plasma cell tumor) but is rarely a treatment option. In cases of weakened bone, metal plates or rods may be placed to support or prevent fractures.

Plasmapheresis uses a machine to filter plasma out of the blood. It is not a treatment for multiple myeloma, but it may be done if large amounts of M-proteins make the blood thick.

Bone-modifying agents are drugs that can treat bone problems caused by multiple myeloma as well as prevent further bone damage from occurring. The collection of myeloma cells in the bone marrow can lead to bone lesions and the destruction of bone. People with smoldering myeloma who have bone loss may take bone-modifying agents during watchful waiting, and people with multiple myeloma may take them as part of their treatment.

Bone health should be addressed proactively, so contact your doctor as soon as you begin to feel any pain. Warning signs of bone loss include joint and back pain, arthritis-like symptoms, slouched posture, shorter stature and broken/fractured bones. Your doctors are devoted to keeping you comfortable and may prescribe medications to help manage it.

Clinical trials may be another treatment option depending on your diagnosis and other factors. New trials that combine novel therapies are underway. Chimeric antigen receptor (CAR) T-cell therapy, a type of immunotherapy that involves modifying a patient’s own T-cells in a laboratory before returning them to the patient, is one example.

Additionally, recent breakthroughs have resulted in improved treatment regimens for people with refractory or relapsed multiple myeloma. Ask your doctor if you are a candidate for a clinical trial. You are also encouraged to research them on your own (See Clinical Trials).

 

Drug Therapies For Multiple Myeloma
As of 9/21/2020
belantamab mafodotin-blmf (Blenrep)
bortezomib (Velcade)
carfilzomib (Kyprolis)
carmustine (BiCNU) 
cyclophosphamide
daratumumab (Darzalex)
daratumumab and hyaluronidase-fihj (Darzalex Faspro)
dexamethasone
doxorubicin hydrochloride (Adriamycin) 
elotuzumab (Empliciti) 
isatuximab-irfc (Sarclisa)
ixazomib (Ninlaro)
lenalidomide (Revlimid)
liposomal doxorubicin (Doxil) 
melphalan (Alkeran)
panobinostat (Farydak) 
pomalidomide (Pomalyst) 
prednisone 
selinexor (Xpovio) 
thalidomide (Thalomid) 
Some Possible Combinations
carfilzomib (Kyprolis) with daratumumab (Darzalex)
carfilzomib (Kyprolis) with dexamethasone or lenalidomide (Revlimid) plus dexamethasone
carmustine (BiCNU) with prednisone
daratumumab (Darzalex) with lenalidomide (Revlimid) and dexamethasone
daratumumab (Darzalex) with bortezomib (Velcade), melphalan (Alkeran) and prednisone
daratumumab (Darzalex) with bortezomib (Velcade), thalidomide (Thalomid) and dexamethasone
daratumumab (Darzalex) with bortezomib (Velcade) and dexamethasone
daratumumab (Darzalex) with pomalidomide (Pomalyst) and dexamethasone
elotuzumab (Empliciti) with lenalidomide (Revlimid) and dexamethasone
elotuzumab (Empliciti) with pomalidomide (Pomalyst) and dexamethasone
isatuximab-irf (Sarclisa) with pomalidomide (Pomalyst) and dexamethasone
ixazomib (Ninlaro) with lenalidomide (Revlimid) and dexamethasone
lenalidomide (Revlimid) with dexamethasone
panobinostat (Farydak) with bortezomib (Velcade) and dexamethasone
pomalidomide (Pomalyst) with dexamethasone
selinexor (Xpovio) with dexamethasone
thalidomide (Thalomid) with dexamethasone

 

Refractory or Relapsed Multiple Myeloma

The goal of treating multiple myeloma is remission. Complete remission is reached when cancer can no longer be found after multiple tests. Even with complete remission, small numbers of cancer cells may still be in the body. A partial remission occurs when some but not all signs and symptoms have decreased or disappeared.

Multiple myeloma tends to return (relapse) after treatment, and sometimes it may stop responding to treatment (refractory).

Relapsed multiple myeloma occurs when the disease comes back after treatment. A relapse can happen weeks, months or even years after initial treatment has ended. Treatments often reduce the amount of myeloma cells, but some can remain undetected and continue to grow.

Refractory myeloma is disease that is no longer responding to treatment. If this happens, your doctor may request additional tests that could be used to restage your multiple myeloma. This is also a good time to consider getting a second opinion.

Keeping follow-up appointments is important because finding any recurrence early is crucial to successful treatment. Your doctor will ask questions about any ongoing symptoms you may have, especially those related to recurrence and long-term side effects of treatment.

Multiple drug therapies are approved to treat these types of multiple myeloma, offering new hope for the possibility of remission. Recent advances in research have resulted in improved treatment regimens for people with refractory or relapsed multiple myeloma, including inhibiting the growth of cancer cells with next-generation proteasome inhibitors, using the immune system to help fight cancer with immunotherapy and altering the immune system with immunomodulatory drugs. Multiple drugs are also being researched in late-stage clinical trials for these types of multiple myeloma.

 

Key Takeaways

  • Many therapies are available to treat multiple myeloma.
  • The goal of treatment is remission.
  • Researchers are studying additional treatments for relapsed and refractory multiple myeloma in clinical trials.

 

Additional Resources

 

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