Significant progress has been made in recent years in understanding multiple myeloma. In addition, new classes of drugs, new drug strategies and combination therapies have changed how doctors approach treating this disease. As a result, more options are available, offering patients hope for living longer.
Because diagnosing and treating multiple myeloma can be challenging, you may want to seek a second opinion or advice from a hematologist or doctors who specialize in treating multiple myeloma. This can happen either before or after diagnosis and even after you begin treatment. Some doctors may favor one treatment approach, while others might suggest a different combination of treatments. There is often collective wisdom gained from the experience and opinions of different oncology specialists who are experts in your type of cancer. A second opinion is also a way to make sure your pathology diagnosis and staging are accurate and that you are aware of clinical trials to consider. You need to learn about all your treatment options.
After your diagnosis is confirmed, you will work with a multidisciplinary team that includes a variety of health care professionals who will be involved in your care.
Developing Your Plan
Reaching remission is the goal of treating multiple myeloma. Remission means no longer having any signs or symptoms of the disease.
Your treatment plan will be based on many factors: whether you are newly diagnosed or are experiencing a recurrence; the presence of symptoms; your overall health; the aggressiveness of the myeloma; and your goals of treatment, which often include reaching remission by eliminating myeloma cells, controlling tumor growth and pain, and improving your quality of life.
For patients with symptoms, a treatment plan may include different phases:
- Induction therapy is designed to control the myeloma and relieve symptoms. It may also be referred to as your primary therapy.
- Consolidation uses more chemotherapy or a bone marrow/stem cell transplant. It can be used for a few cycles after the first therapy and before maintenance therapy with the goal of deepening the response to the induction phase.
- Maintenance therapy is given to prevent cancer recurrence over a prolonged period of time. It may include one or more drugs that are typically oral therapies.
Be aware that it is common for the treatment strategy you begin with to change. Your doctor will continually monitor your condition and make adjustments for a number of reasons. Sometimes a therapy becomes less effective as time goes on; other times, a new mutation may be discovered and a different therapy may offer more promise; or you may reach remission, among other things. Keep in mind that cancer is a fluid condition that presents many challenges, so flexibility and patience are important.
Based on the stage of the disease and your age, overall health, symptoms, previous treatments and preferences for quality of life, one or more of the following therapies may be recommended.
Watchful waiting may be recommended for people with monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (both precursors to multiple myeloma), early-stage disease and when symptoms are not present. It offers the possibility of avoiding the side effects of treatment as long as possible and, hopefully, without affecting the outcome. Keep regular checkups because treatment should begin as soon as the disease progresses or symptoms appear.
Drug therapies are commonly used to treat multiple myeloma. These therapies are known as systemic because they travel throughout the body. They may be delivered orally, intravenously and subcutaneously (beneath the skin) (see Figures 1 and 2). Drug therapies include chemotherapy, immunotherapy, targeted therapy, corticosteroids and bone-modifying drugs.
Chemotherapy is commonly used for multiple myeloma, and most people receive some form of it. It uses drugs to destroy cancer cells by preventing them from growing and dividing. It may consist of a single drug or multiple drugs given in combination. It may also be combined with other types of treatment. Some oral chemotherapy drugs may be taken at home. Intravenous (IV) drugs are given in a doctor’s office, clinic or hospital. When given as supportive care, chemotherapy may also be used to reduce back pain caused by osteoporosis or compression fractures of the spine.
Corticosteroids are myeloma cell-fighting drugs that may ease chemotherapy side effects, particularly nausea and vomiting. They can be used alone or in combination with chemotherapy. Corticosteroids also help reduce inflammation and may offer other benefits.
Immunotherapy is drug therapy that works with your immune system to help identify and then destroy multiple myeloma cells. It may be given by IV or subcutaneously (by injection under the skin). The following types of immunotherapy are approved.
- Monoclonal antibodies (mAbs) are made to target specific antigens — in this case, ones found on myeloma cells. The mAbs can be made to recognize and attach to proteins and other substances on multiple myeloma and other cells or deliver other therapeutic agents to slow their growth and/or kill them. They might also enable your immune system to learn to identify and destroy multiple myeloma cells.
- Chimeric antigen receptor (CAR) T-cell therapy involves taking a patient’s T-cells and modifying them to recognize and kill multiple myeloma cells (see Figure 4, page 10).
A combination of immunotherapy drugs may also be used to treat amyloidosis.
Targeted therapy drugs are used to slow or stop the progression of disease. These drugs may be given orally, subcutaneously or by IV. They travel throughout the body via the bloodstream looking for specific proteins and tissue environments of myeloma cells.
Targeted therapy may also be given as supportive care to decrease the amount of immunoglobulin M, a type of antibody, and to treat amyloidosis. Targeted therapy with a monoclonal antibody may also be given to slow bone loss and reduce bone pain.
The following drugs may be used alone or in combination with corticosteroids, immunomodulators and other therapies:
- Angiogenesis inhibitors block new blood vessel growth that feeds myeloma cells.
- Histone deacetylase (HDAC) inhibitors affect gene expression inside myeloma cells.
- Immunomodulators may stimulate or slow down the immune system in indirect ways. They may boost the immune system and the effects of other therapies on the myeloma cells. They may be effective in treating newly-diagnosed multiple myeloma and relapsed or refractory disease.
- Monoclonal antibodies (mAbs) are commonly used. Laboratory-made mAbs attach to specific proteins and attack myeloma cells.
- Proteasome inhibitors target enzymes to slow or stop myeloma cell growth and development.
- Selective inhibitors of nuclear export (SINE) enhance the anticancer activity of certain proteins in a cell.
Bone-modifying (strengthening) drugs can treat bone problems caused by multiple myeloma as well as prevent further bone damage from occurring. Myeloma cells in the bone marrow can lead to bone lesions and the destruction of bone. Contact your doctor as soon as you begin to feel any pain.
Stem cell transplantation may be recommended (see Stem Cell Transplantation, page 11). An autologous (auto) transplant uses the patient’s own stem cells, which are collected, filtered, processed and frozen. High-dose chemotherapy and sometimes full-body radiation therapy (conditioning) are given to destroy cancer cells. Then the reserved stem cells are thawed and infused back into the patient’s body. This therapy may also be used to treat amyloidosis. Another option that may be used is an allogeneic (allo) transplant.
Radiation therapy may be used for localized myeloma or bone pain that does not lessen with chemotherapy (see Figure 3).
Surgery may be used to treat a plasmacytoma (malignant plasma cell tumor) but is rarely a treatment option. In cases of weakened bone, metal plates or rods may be placed to provide support or to prevent fractures.
Plasmapheresis uses a machine to filter plasma out of the blood. Though not a treatment for multiple myeloma, it may be used if large amounts of M-protein make the blood thick.
Clinical trials are medical research studies that may offer access to therapies not yet widely available. Most cancer treatments used today were once developed, tested and evaluated through the clinical trials process to gain approval from the U.S. Food and Drug Administration (FDA).
Multiple myeloma is an active area of research with many trials underway, such as those involving bispecific T-cell engagers (BiTEs), which enable a cancer-fighting T-cell to bind to and kill cancer cells. Other areas of research include testing new combinations of currently approved drug therapies; investigating a new type of CAR using natural killer (NK) cells as well as other CAR T-cell therapies; integrating other myeloma therapies for treating relapsed and refractory patients; finding better ways of detecting, monitoring and treating side effects; and developing a next-generation immunomodulator.
Volunteering for a trial may be your best option if your cancer has become resistant to your current treatment. It offers a higher level of care because you will be monitored by the medical team managing your trial as well as by your regular oncologist. And you are helping improve treatments for other patients.
Ask your doctor if you are a candidate for a clinical trial and whether you should consider one at any time during your treatment.
Monitoring Treatment Response
Part of treating multiple myeloma will be ongoing monitoring of your treatment and health status. This ensures that your treatment is working and that the disease has not developed resistance to the medications. One way to prevent resistance is through the use of several drugs together. This may include two, three or four drugs. It is common for multiple myeloma patients to receive more than one drug.
As part of your monitoring, your doctor may use measurable/minimum disease residual (MRD) testing to measure a treatment’s effectiveness. MRD is used to describe a very small number of cancer cells that remain in the body during or after treatment. MRD can be found only by highly sensitive laboratory methods that are able to find one cancer cell among one million normal cells. Checking for MRD may help plan treatment, find out how well treatment is working, detect whether cancer has come back or make a prognosis.
When residual cancer cells are still detectable in the blood, this is known as being “MRD positive.” When no cancer cells can be found, it is known as being “MRD negative.” Research studies have shown that MRD negativity is associated with longer remissions.
Your doctor may use the term “durable response” to describe a response to treatment that lasts longer than expected. It is typically seen with the use of immunotherapy drugs.
Most maintenance therapies are given orally, making it crucial for you to take your medication on time. Though oral therapies offer great convenience, it is critical to understand the importance of taking them exactly the way your doctor instructs. To be fully effective, every dose must be taken with the same kind of accuracy, precise timing and safety precautions as infusions and injections, for as long as prescribed. This is known as medication adherence.
Medication adherence is important because most cancer therapies are designed to maintain a specific level of drugs in your system for a certain time based on your cancer type and stage, your overall health, previous therapies and other factors. If your medications are not taken exactly as prescribed, or if you miss appointments for your infusions or injections, the consequences can be serious, even life-threatening.
Common Drug Therapies for Multiple Myelomas
These therapies may be used alone or in combination.
|Drug Therapies For Multiple Myeloma|
|belantamab mafodotin-blmf (Blenrep)|
|daratumumab and hyaluronidase-fihj (Darzalex Faspro)|
|doxorubicin hydrochloride (Adriamycin)|
|doxorubicin liposomal (Doxil)|
|idecabtagene vicleucel (Abecma)|
|Some Possible Combinations|
|carfilzomib (Kyprolis) with dexamethasone or lenalidomide (Revlimid) plus dexamethasone|
|carmustine (BiCNU) with prednisone|
|daratumumab and hyaluronidase-fihj (Darzalex Faspro) with bortezomib (Velcade) and dexamethasone|
|daratumumab and hyaluronidase-fihj (Darzalex Faspro) with bortezomib (Velcade), melphalan and prednisone|
|daratumumab and hyaluronidase-fihj (Darzalex Faspro) with bortezomib (Velcade), thalidomide (Thalomid) and dexamethasone|
|daratumumab and hyaluronidase-fihj (Darzalex Faspro) with lenalidomide (Revlimid) and dexamethasone|
|daratumumab and hyaluronidase-fihj (Darzalex Faspro) with pomalidomide and dexamethasone|
|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|
|isatuximab-irfc (Sarclisa) with carfilzomib and dexamethasone|
|ixazomib (Ninlaro) with lenalidomide (Revlimid) and dexamethasone|
|lenalidomide (Revlimid) with dexamethasone|
|liposomal doxorubicin (Doxil) with bortezomib (Velcade)|
|panobinostat (Farydak) with bortezomib (Velcade) and dexamethasone|
|pomalidomide (Pomalyst) with dexamethasone|
|selinexor (Xpovio) with dexamethasone|
|thalidomide (Thalomid) with dexamethasone|
Educate yourself about relapsed and refractory multiple myeloma
The primary goal of treating multiple myeloma is to reach 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.
It is common to hear doctors refer to multiple myeloma that has come back after treatment as relapsed. 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.
Keeping follow-up appointments is important because finding a recurrence early is key to successful treatment. At your follow-up appointments, your doctor will ask questions about any ongoing symptoms you may be having, especially those related to recurrence and long-term side effects of treatment.
Refractory myeloma is multiple myeloma that stops responding to treatment. The disease may not respond to initial therapy or may stop responding after treatment has been underway for a length of time. If this happens, your doctor may request additional tests that could be used to restage your multiple myeloma. If a new stage is assigned, it will likely change your treatment options. This is also a good time to consider getting a second opinion.
Resistance to some drug therapy and genetic abnormalities in myeloma cells are two common causes of refractory myeloma. A treatment plan for refractory myeloma may use a combination of therapies, which is designed to prevent or slow the development of drug resistance.
Another option may be a clinical trial. Research is ongoing to find new treatment combinations that are effective. Recent advances in research have resulted in improved treatment regimens for people with refractory or relapsed multiple myeloma. Ask your doctor if you may be a candidate for a clinical trial.
Treatments are often referred to in the order they are typically given. First-line therapy is the first therapy given. It is often the standard of care for the diagnosis, which is the treatment most commonly used. Second-line therapy is given when the first-line therapy doesn’t work or stops being effective. It is common for multiple myeloma patients to have third- and fourth-line therapies when the disease comes back or a treatment stops working.