Multiple Myeloma

Treatment Planning

Recent advances in treatment strategies offer promise and hope for people with multiple myeloma and their loved ones. Through clinical trials, new and more effective options designed to treat and manage multiple myeloma are becoming available with the goal that one day there will be a cure. As you and your doctor discuss a treatment plan, make it a priority to share your expectations for your quality of life and how you may be able to achieve it.

Because diagnosing and treating multiple myeloma can be challenging, finding a blood cancer specialist with expertise in treating multiple myeloma is highly recommended. A general hematologist/oncologist can give you a referral to a specialist.

You may also want to seek a second opinion or advice from a hematologist or doctor who specializes in treating multiple myeloma. This can happen either before or after diagnosis and even after you begin treatment. One doctor may favor one treatment approach, while another might suggest a different combination of treatments. 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.

Possessing flexibility and patience is very important because this cancer is often managed as a chronic disease. It may be helpful to talk to others with multiple myeloma. Learning how they have managed it can help you adopt a positive attitude and move forward more confidently.

Getting Started

You will hear a lot of new information. Some of the terms your medical team uses may be confusing. These explanations may help you feel more informed as you make the important decisions ahead. 

  • First-line therapy is the first treatment used.
  • Second-line therapy is given when the first-line therapy does not work or is no longer effective.
  • Standard of care refers to the widely recommended treatments known for the type and stage of cancer you have.
  • Local treatments are directed to a specific organ or limited area of the body and include surgery and radiation therapy.
  • Systemic treatments travel throughout the body and are typically drug therapies, such as chemotherapy, targeted therapy and immunotherapy.
  • Doublet therapy is a combination of two drugs, such as an immunomodulatory agent and a corticosteroid.
  • Triplet therapy is a combination of three drugs with different mechanisms of action, such as a proteasome inhibitor or chemotherapy drug, along with an immunomodulating agent and corticosteroid.
  • Quadruplet therapy adds a fourth drug with another mechanism of action to a different target.

Making Your Plan

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.

It is common for your treatment strategy to change over time. 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 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.

Treatment Options

Reaching remission is the objective of treating multiple myeloma. Remission means no longer having any signs or symptoms of the disease. Your doctor will develop your treatment plan using one or more of the types of therapies explained on the next page. The goal is for you to receive the best level of care possible.

One or more of the following therapies may be used.

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 or subcutaneously (by injection under the skin) (see Figures 1 and 2). Drug therapies include chemotherapy, immunotherapy, targeted therapy, corticosteroids and bone-modifying drugs.

Chemotherapy destroys cancer cells by preventing them from growing and dividing. It is commonly given for multiple myeloma, and most people receive some form of it. 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.

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.

Figure 5

Immunotherapy works with your immune system to help identify and then destroy multiple myeloma cells. It may be given by IV or subcutaneously. A combination of immunotherapy drugs may also be used to treat amyloidosis.

The following types of immunotherapy may be options:

  • 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.
  • Bispecific mAbs are made up of two different mAbs that can attach to two different antigens at the same time and can be delivered without removing a patient’s immune cells (see Figure 4). They can be used for engaging and activating immune cells, such as T-cells, to attack a tumor, block dual signaling pathways, block immune checkpoints or form a way to replace a missing functional protein. Many of these are known as bispecific T-cell engagers (BiTEs).
  • 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 5).

Targeted therapy attacks certain cancer cells and avoids healthy cells, resulting in fewer side effects than with traditional chemotherapy. 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.

The following drugs may be used alone or in combination with other therapies:

  • Angiogenesis inhibitors block new blood vessel growth that feeds myeloma cells.
  • BCL-2 inhibitors block the BCL-2 protein, which is found in 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.
  • Bispecific mAbs are made up of two different mAbs that can attach to two different antigens at the same time and can be delivered without removing a patient’s immune cells.
  • Proteasome inhibitors target enzymes to slow or stop myeloma cell growth and development.
  • Selective inhibitors of nuclear export (SINE) enhance the anti-cancer 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. 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 is an allogeneic (allo) transplant, which uses donor cells.

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 involves using a machine to filter plasma. Though it is not a treatment for multiple myeloma, it may be used if large amounts of M-protein make the blood too thick.

Clinical trials may offer the opportunity to try an innovative treatment that is testing a variety of therapies before they are 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).

Many clinical trials for novel multiple myeloma treatments are taking place today. It is an active area of research that is testing new drugs, new modes of action and new combinations of currently approved drug therapies. Current trials are focused on a new type of chimeric antigen receptor (CAR) using natural killer (NK) cells as well as other CAR T-cell therapies; therapies for treating relapsed and refractory myeloma; better methods of detecting, monitoring and treating side effects; and a next-generation immunomodulator.

A clinical trial may be your best option if your cancer has become resistant to your current treatment or if you have already had multiple lines of therapy. 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.

Ongoing Monitoring 

Treating multiple myeloma will include ongoing monitoring of your treatment and health status to evaluate whether your treatment is effective 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 doublet, triplet or quadruplet therapy. It is common for multiple myeloma patients to receive more than one drug.

As part of your monitoring, your doctor may use measurable/minimum residual disease (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 identify appropriate treatment, determine 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.

Because treatments for multiple myeloma are improving, a patient may have a very long remission. That might be referred to as a “durable response.” It is typically seen with the use of immunotherapy drugs.

Common Drug Therapies for Multiple Myelomas

These therapies may be used alone or in combination. 

Drug Therapies For Multiple Myeloma
bortezomib (Velcade)
carfilzomib (Kyprolis)
ciltacabtagene autoleucel (Carvykti)
carmustine (BiCNU)
daratumumab (Darzalex)
daratumumab and hyaluronidase-fihj (Darzalex Faspro)
doxorubicin hydrochloride (Adriamycin)
doxorubicin liposomal (Doxil)
elotuzumab (Empliciti)
elranatamab-bcmm (Elrexfio)
idecabtagene vicleucel (Abecma)
isatuximab-irfc (Sarclisa)
ixazomib (Ninlaro)
lenalidomide (Revlimid)
melphalan (Alkeran)
panobinostat (Farydak)
pomalidomide (Pomalyst)
selinexor (Xpovio)
talquetamab-tgvs (Talvey)
teclistamab-cqyv (Tecvayli)
thalidomide (Thalomid)
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
As of 8/15/23

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. However, 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.

Relapsed myeloma is disease that has come back after treatment. A relapse can happen weeks, months or even years after initial treatment has ended. Keeping follow-up appointments is important because finding a recurrence early is key to successful treatment.

Refractory myeloma occurs when the cancer 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.

Treatment Terminology

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.

The importance of medication adherence

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, injections or radiation therapy, the consequences can be serious, even life-threatening. To be fully effective, every treatment dose must be taken with the same kind of accuracy, precise timing and safety precautions, for as long as prescribed. This is known as medication adherence.