Treatment Options

The physician responsible for treating your myeloma will provide more current information than is available here. The Myeloma Survival Guide, on sale where ever books are sold and available in public libraries, may also be helpful.


Chemotherapy

Chemotherapy is the systematic, repetitive use of drugs to stop the growth of cancer cells, either by killing them or slowing their growth throughout the body. Since multiple myeloma is usually widespread at the time of diagnosis and is very sensitive to chemotherapy, it is used to treat most patients. 

Traditional chemotherapy is the use of cytotoxic drugs which aim to kill cancer cells directly and has been the standard treatment for multiple myeloma for decades. These drugs incude  melphalan (Alkeran), cyclophosphamide (Cytoxan), vincristine (Oncovin), doxorubicin (Adriamycin) and liposomal doxorubicin (Doxil)

Administered through an intravenous (IV) injection or infusion or taken orally, chemotherapy is usually given in cycles over a period of months, followed by a rest period. It should be continued until the patient is in a plateau, or remission state with stable M-protein levels and no evidence of progression of the disease. (Multiple myeloma cells produce excessive monoclonal proteins known as M-proteins, which can be detected in a blood or urine sample.) The patient may need chemotherapy again if their M-protein level begins to rise.

Combinations of chemotherapy drugs are more effective than any single drug and are often combined with other types of drugs like corticosteroids or immunomodulating agents. Since the drug melphalan tends to damage the bone marrow it is usually avoided initially if the patient is a candidate for stem cell transplant.

Corticosteroids

Another class of drugs, corticosteroids, have also been used for decades to treat multiple myeloma causing programmed death of certain types of cells. They are typically used in combination with chemotherapy drugs and are administered in pill form. The most commonly-used drugs for myeloma in this category are  predisone and  dexamethasone (Decadron).

Steroids--particularly prednisone--are perhaps the single most helpful group of drugs for the treatment of myeloma. They shrink myeloma tumors, known as plasmacytomas, reducing neurologic pressure, which relieves pain. They also reduce hypocalcaemia--too much calcium in the blood. This can be a God-send, easing constipation, nausea, stomach pain, poor appetite, and vomiting. Kidney pain can be reduced. Frequent thirst and frequent urination are relieved. Kidney stones are less apt to form.

In patients with renal failure, steroids can be used without dose adjustment. In patients who have low blood counts, they can be used without fear of further reduction in counts.

 

Immunomodulating agents (IMiDs)

Immunomodulating agents (IMiDs), thalidomide (Thalomid) and lenalidomide (Revlimid), work with the body's immune system to prevent myeloma cells from binding to bone and forming tumors. These drugs are also known as anti-angiogenesis agents, as they block a substance needed for blood vessel growth (known as angiogenesis). Some cancer tumors require new blood vessels for growth and when these blood vessels are blocked, the tumor subsequently dies. A promising new drug in this class, pomalidomide (Pomalyst), was approved by the FDA in early 2013.

Thalidomide (Thalomid) was used in the 1950s as a sedative and to treat morning sickness but was banned because it caused severe birth defects. The drug was approved by the FDA in 1998; and, in May of 2006, was approved for the treatment of newly diagnosed multiple myeloma. It has also been found to be effective in treating myeloma that does not respond to chemotherapy.

A newer, stronger drug, lenalidomide (Revlimid), was approved by the FDA in 2006. It is currently used more often than  thalidomide as it appears to be more potent and cause fewer side effects. It was approved in combination with  dexamethasone for people with previously treated myeloma, but is also often used for people with newly diagnosed disease. Both drugs are administered orally.

 

Proteasome inhibitors

Bortezomib (Velcade) is the first in a new class of drugs called proteasome inhibitors which work by blocking the enzyme complexes (proteasomes) in myeloma cells and disrupting the breakdown of proteins that are important for keeping cell division under control. The FDA approved Velcade in 2008 as a treatment option for all newly diagnosed and previously treated patients with multiple myeloma. It is administered as an IV injection. A second-generation proteasome inhibitor, carfilzomib (Kyprolis), was approved by the FDA in July of 2012 for use in patients with relapsed and refractory multiple myeloma.

Chemotherapy & Drug Side Effects

Chemotherapy works by destroying rapidly growing cancer cells; unfortunately, they also affect other rapidly growing cells, such as blood cells that fight infection, cells lining the mouth and digestive tract, and cells in hair follicles. The side effects that may occur include the following:

 

Chemotherapy
  • decreased resistance to infection
  • fatigue
  • nausea
  • vomiting
  • diarrhea or constipation
  • loss of appetite or weight
  • mouth sores
  • hair loss or thinning.
Corticosteroids
  • high blood sugar
  • increased appetite
  • fluid retention
  • weight gain
  • problems sleeping
  • mood changes
Prolonged usage may cause the onset of diabetes, contribute to osteoporosis (thinning of the bones), and suppression of the immune system, leading to an increased risk of serious infections.
 
Immunomodulating Agents
  • drowsiness
  • fatigue
  • blood clots
  • constipation, and
  • peripheral neuropathy--a nerve condition that causes tingling sensations, numbness or weakness, usually in the hands and feet.
Because of severe birth defects if taken during pregnancy, access to these drugs is tightly controlled.

Proteasome Inhibitors
  • fatigue
  • fever
  • nausea
  • vomiting
  • constipation or diarrhea
  • neuropathy
  • decreased platelet blood count which may cause bruising and bleeding.


You may have none of these side effects or just a few. Much of it depends on the type and dose of drugs given and the length of time they are taken; however no one knows exactly how your body will react until you begin your chemo. The side effects of chemotherapy usually go away after treatment ends, but the time it takes depends on many things, including your overall health and the kind of chemotherapy you have been taking.

It is important to note that side effects are not a sign of how well the drugs are working against your cancer.

 

Frontline Treatment Options

Compounds most effectlvely used to combat myeloma are divided into two groups:

1. Those given to patients who are eligible for stem cell transplants; and
2. Drugs given to patients who are not eligible.

 

FRONTLINE TREATMENT OPTIONS - Transplant Eligible
FRONTLINE THERAPY ADVANTAGES DISADVANTAGES
VAD
(Vincristine/Adriamycin/Dexamethasone)
Produces remission in 70% of patients
Doesn't damage normal stem cells Can be basis for stem cell transplant
Needs central line catheter for IV administration. The catheter can trigger infection and blood clot complications
Vincristine can cause nerve damage New options are available that are more effective and less toxic
Dexamethasone plus Thalidomide* An oral approach producing remission in 70% of patients New gold standard for frontline induction Neuropathy and deep vein thrombosis (blood clots) are potential concerns
R or RD or Rd (RevloDex)*
(Revlimid® alone, with Dexamethasone, or Revlimid® with low dose Dexamethasone)
Excellent response rates
Generally well-tolerated
Revlimid® alone can result in less effective response
Risk of blood clot problems; requires aspirin or another blood thinner Possible reduced stem cell harvest
VELCADE®** Shows remarkable benefit
Many combinations available Preferred in cases of renal compromise/abnormal genetic features
Produces neuropathy that is partially or completely reversible in this setting
VTD
(VELCADE®/Thalidomide/Dexamethasone)
Very high response rate in recent phase III trial Excellent outcomes posttransplant Intravenous combination Potential for side effects: peripheral neuropath
More Complex VELCADE® Combos
(with Revlimid®, Doxil®, or other agents)
Excellent response rates Intravenous combinations Possible increased toxicities with uncertain benefits
  * Can be used with or without plan for harvest and transplant
** In June 2008, VELCADE®'s approval was expanded to include previously untreated myeloma patients.
FRONTLINE TREATMENT OPTIONS TABLE - Transplant Ineligible
FRONTLINE THERAPY
ADVANTAGES
DISADVANTAGES
MP
(Melphalan/Prednisone)

Taken by mouth
Well tolerated
Produces excellent remissions in about 60% of patients
Physicians very familiar with protocol

Can cause bone marrow stem cell damage and therefore reduce chances of successful stem cell transplant Full benefit occurs slowly over several months Not ideal if prompt response required and/or if stem cell transplant planned
Dexamethasone plus Melphalan In combination with melphalan, produces more rapid benefit than MP The use of melphalan up-front damages stem cells Dexamethasone can be difficult for older patients
MPT
(MP + thalidomide)
Taken by mouth
Well tolerated Higher remission rate than MP
Same as for MP
Thalidomide has risks of neuropathy and/or blood clot problems (DVT)
VMP
(VELCADE® + MP)
Generally well tolerated No blood clot risk Higher remission rate than MP Same as for MP VELCADE® is I.V. Significant risk of neuropathy
MPR
(MP + Revlimid®)
Taken by mouth
Well tolerated Higher remission rate than MP
Risk of blood clot problems with Revlimid®. Aspirin or another blood thinner required

A variety of other therapies are sometimes used such as Cytoxan® (cyclophosphamide) and Etoposide® (VP-16).

Potential combinations include:

  • VBMCP (M2 protocol)
  • VMCP/VBAP (SWOG protocol)
ABCM (UK MRC protocol)
Combinations provide a more aggressive approach, if deemed necessary Symptoms of active disease may be controlled more rapidly and quality of first remission may be better More side effects than simpler regimens
No added longer-term benefit Side effects may both reduce quality of life and compromise eligibility for new protocols

* In June 2008, VELCADE®'s approval was expanded to include previously untreated myeloma patients.

Further details about treatment options are available in other IMF publications.
To order these, please contact the IMF or visit: www.myeloma.org

Frontline Treatment Options prepared jointly by Brian G. M. Durie, MD, International Myeloma Foundation, and Artur Jurczyszyn, MD PhD, Clinic of Haematology, University Hospital, Cracow, Poland.


Stem Cell Transplant

A stem cell transplant (SCT) is a procedure in which diseased bone marrow is replaced by stem cells which are found both in the bloodstream and in the bone marrow. They develop into all types of blood cells, theoretically as your body needs them, though fewer and fewer are produced as we age. 

The goal of SCT is to destroy cancer cells in the marrow, blood, and other parts of the body, then allow replacement blood stem cells to generate healthy new bone marrow throughout the body.

In the past, stem cells were collected directly from bone marrow which required a surgical operation under anesthesia. Today the stem cells are collected through a procedure called "apheresis," in which blood is removed through a needle in your vein, similar to the needle used in a blood transfusion.

SCT can be done using the patient’s own stem cells (autologous transplant) or using cells from a close relative or matched unrelated donor (allogeneic transplant). Allogenic transplants pose a greater risk to the patient, due to graft-versus-host-disease (GVHD) which can be life-threatening. Sometimes, allogeneic transplants can be performed after giving lower doses of chemotherapy and/or radiation therapy that are still sufficient to suppress the immune system and allow growth of the donor cells. These are known as “mini-transplants” and rely on the donor's immune system cells to fight the patient’s cancer cells through graft-versus-tumor (GVT) effect. These mini-transplants have less immediate side effects, allowing the procedure to be used for older patients.

The SCT process begins with injections of growth factor drugs to encourage large amounts of stem cells to develop. Once the white blood cell count is high enough, the patient's stem cells are harvested through apheresis. The blood is then circulated through a cell separator that removes the stem cells and lets the rest of the blood flow back into the bloodstream. The procedure is painless and can be done in an outpatient setting. It usually takes several sessions of two to four hours each to get enough stem cells. The stem cells are then preserved by freezing them while the patient receives high-dose chemotherapy and sometimes whole-body radiation to destroy the existing bone marrow. 

The cancer is theoretically obliterated. The patient is also left without much defense against disease or infection. Red blood cells, which transport the body’s oxygen; white cells, the body’s first defense against infection; and blood platelets, which stop bleeding; are all dangerously depleted. Until the patient’s immune system is back to normal, patients may need antibiotics and blood transfusions.

Transplants take place in a special, highly antiseptic section of a hospital. New healthy, blood-producing tissue develops in ten days to three weeks, along with a rejuvenated immune system. Direct contact with the patient is carefully controlled until a new immune system has kicked in.

Q?
What are the advantages of a stem cell transplant?
A.
Stem cell transplants are an important treatment option for people with multiple myeloma as they often lead to longer remissions and longer survival than other types of treatments. A stem cell transplant enables the patient to be treated with high doses of drugs designed to destroy cancer cells more effectively than standard chemotherapy. The new blood cells that develop from the transplanted stem cells replace the ones that were destroyed by treatment, theoretically eradicating the cancer and jump-starting the immune system.

Thalomid, Revlimid, and Velcade, used in combination with malignant cell-killing therapies, are sometimes used in preference to, or as a substitute for, stem cell transplants. However, compared with chemotherapy alone, a stem cell transplant is more likely to produce a longer progression-free survival, according to many of myeloma's leading therapists.

Latest research indicates that people who undergo stem cell transplants along with maintenance chemotherapy for myeloma treatment have a better chance of both improvement of their cancer and survival compared with people who get conventional chemotherapy or a stem cell transplant alone.

Q?
How long does it last?
A.
It typically takes about one year for the blood and immune system to return to normal levels after a stem cell transplant. This procedure will often put the myeloma into remission; however, the majority of patients will continue to show evidence of myeloma even after the stem cell transplant. 

Though some patients have remained symptom free ten, even fifteen years after transplant, all patients will eventually develop myeloma again. The average time before relapse is now over five years.

Q?
Can it be done more than once?
A.
Some doctors now recommend that patients have a tandem transplant, meaning a second autologous stem cell transplant within six months of the first. Studies show that tandem transplants can double the rate of both event-free (no relapse) and overall survival as compared with a single autologous transplant. 

In other cases, more than one transplant may be recommended if the disease has relapsed. Patients who have successfully undergone an autologous stem cell transplant and remain healthy may be candidates for a second transplant procedure, particularly if an adequate number of previously harvested stem cells are still available.

Q?
What are the side effects?
A.
There are several potential side effects of stem cell transplantation, due primarily to the high-dose chemotherapy part of the transplant preparation process. These include nausea, vomiting, diarrhea, mouth sores, hair loss and skin rashes. Since the blood-producing cells in the bone marrow have been destroyed, patients are also susceptible to infection, anemia and bleeding until engraftment is complete.

Other, more serious complications can occur and include organ damage, secondary cancers, cataracts, and for a percent or two, death. Graft failure (your immune system attacks the donated stem cells) and graft-versus-host-disease (GVHD) where donated stem cells attack the patient’s tissues, can occur with donor (allogeneic) transplants and can affect the digestive tract, liver or skin. These complications can be minor or life threatening and can happen soon after transplant or develop slowly over months.

Q?
Where is this done with the greatest success?
A.
Three medical institutions are noted for early leadership in this technology and very high volumes of successful work:

Mayo Clinic, Rochester, MN; University of Arkansas Medical Center, Bartletsville, AR; and MD Anderson Cancer Center, Houston, TX There are other fine institutions to consider. Ask your doctor for recommendations


Radiation

Radiation is a general term for any of a great many methods that use beams of high-energy X-rays or particles (photon, electron, proton, neutron, or ion) to shrink or kill cancer cells.

Radiation damages the genetic material of cells in the area being treated, leaving the cells unable to continue to grow. Although radiation damages normal cells as well as cancer cells, the normal cells usually can repair themselves while the cancer cells, theoretically, cannot.

When used to treat multiple myeloma, radiation treatment can be administered locally or to the whole body. In local radiation, a large machine aims radiation at the bone or the part of the body where myeloma cells (plasmacytoma) have collected and only affects cells in the treated area. In total-body radiation patients receive radiation to their whole body in preparation for stem cell transplantation.

Sometimes the goal of radiation therapy is to destroy tumors that have spread to other parts of the body or to reduce the risk that cancer will return after undergoing surgery or chemotherapy. In other cases, it may be used as a palliative treatment, meaning that the goal is to reduce the symptoms caused by growing tumors and to improve your quality of life. Examples of this would be relieving pain by reducing the size of a tumor or to shrink a lung tumor that is causing shortness of breath.

It is essential for you, as a patient, to know the objectives of the radiation therapy you receive and to discuss the goal of your treatment with your radiation oncologist. If the explanation you get is not clear to you, stop the proceedings and get clarification. Perhaps because of the impressive size of the equipment, it is easy to assume that there will be more lasting benefit than may be the case.

Radiation Side Effects

Side effects of multiple myeloma radiation treatment will depend on the dose of radiation and the part of your body that is treated. For example, radiation to the lower back may cause nausea, vomiting, or diarrhea when the lower digestive tract is exposed to radiation during the treatment process. Skin in the treated area may also become red, dry, and tender. 

The side effect most often reported by patients receiving radiation is fatigue--a feeling of extreme tiredness and low energy. The tiredness that patients experience is usually mild or moderate and is different for each one. 

Side effects of radiation therapy can usually be treated or controlled and will, in most cases, go away after treatment ends.


Surgery

The surgeries most often needed by myeloma patients are minor, as operations go. Most likely procedures are used to diagnose the disease (biopsy), remove a plasmacytoma (tumor), or relieve pressure from a tumor on the spine or an organ.

Orthopedic surgery also may be used to repair damage to the bones, most commonly in the skull, jaw, hands, feet, or spine. More recently, procedures such as vertebroplasty or kyphoplasty (inflating and injecting bone cement into the vertebral bodies) have been used to relieve pain, restore lost height from collapsing vertebral bodies, and strengthen the spine.

It is important to note that surgery will not cure multiple myeloma. The primary goal is to decrease pain and maintain function, thereby increasing your quality of life. It is almost always done in conjunction with radiation therapy or chemotherapy. Age, overall health, and physical limitations will also be considered before undergoing surgery. Be sure you and your doctor discuss the risks of the procedure, anesthesia and any potential complications arising from the surgery.

There is a commonly repeated myth that cancer cells are spread by exposure to air. Not true. Surgery can, however, spread cancer, and so special, very successful precautions are taken to prevent it.


Supportive Treatments

Unlike other types of cancer, the build-up of myeloma cells do not just produce tumors; they release many proteins and other chemicals into the bone marrow and directly into the blood stream, causing other complications. Early use of supportive care treatments may be just as important as initiating frontline therapy.

Anemia

Anemia is a common complication of multiple myeloma and occurs when the patient’s body does not have enough red blood cells and/or hemoglobin, the oxygen-carrying protein these cells produce. Abnormal plasma cells, or myeloma cells, crowd the bone marrow and prevent it from making enough red blood cells. Patients with anemia may experience tiredness, fatigue, and shortness of breath.

To help with these symptoms, Procrit (erythropoietin) or Aranesp (darbepoetin alfa) may be prescribed to help the bone marrow produce more red blood cells. In severe cases, patients may be given intravenous red blood cell transfusions in order to raise dangerously low hemoglobin levels.

Hypercalcemia

Myeloma patients often develop an increased level of calcium in the bloodstream known as hypercalcemia which results from the destruction of bone due to bone destroying lesions. Hypercalcemia causes fatigue and lethargy and is typically treated with bisphosphonates and the drinking of ample fluids. Severe hypercalcemia is a medical emergency requiring immediate treatment.

Bisphosphonate drugs can prevent the bone loss that results from bone lesions, thereby reducing the risk of fractures and decreasing pain. Bisphosphonate drugs that may be prescribed include Zometa (zoledronic acid) and Aredia (pamidronate). Both are given intravenously, or directly into a vein.

With ongoing bisphosphonate use, a small fraction of patients may develop problems with kidney function or damage to the jawbone (osteonecrosis). It is a good idea to discuss these side effects with your doctor and ask if urine and/or blood tests will be used to monitor whether or not your kidneys are being affected. Regular dental visits can help in guarding against jaw damage, or catching it early if it develops.

Infections

Myeloma patients are often at increased risk for infection due to the depletion of normal white blood cells and must be careful to stay away from people with colds and other communicable sicknesses. If you experience recurrent infections or you have a low white blood cell count, your doctor may prescribe a colony-stimulating factor to encourage the production of white blood cells. These include Neupogen (filgrastim)Neulasta (pegfilgrastim), and Leukine (sargramostim).

If you develop an infection, it may require treatment with antibiotics or intravenous immunoglobulin therapy. This involves receiving a mixture of antibodies (infection-fighting proteins) made from donated human plasma to help boost your immune system. Possible signs of infection include high fever (above 100.5° F), chills or sweats, cough, sore throat, mouth sores, changes in your urine or stools, or just an overall sick feeling. It is important to notify your doctor if you experience any of these symptoms.

Kidney Problems

Myeloma cells also can produce proteins called “light chains” or “Bence Jones proteins” after the British physician who discovered them. These proteins may accumulate and clog the kidney, damaging it, and ultimately causing it to fail. Excess calcium in the blood (hypercalcemia) causes fluid loss and dehydration and may make these conditions worse. Therefore, it is important to drink enough fluids to help prevent kidney failure. Ask your doctor if you should avoid NSAIDS (nonsteroidal anti-inflammatory drugs) such as Motrin and Advil, which may worsen kidney function.

These “light chain” proteins can also affect the heart, liver, spleen, and in some cases, cause these organs to fail. Clinical trials are now under way to determine the best ways to treat these conditiosn.

In addition to the management of specific symptoms, critically important supportive measures include physical activity for improved bone strength, eating a healthy diet, and maintaining regular sleep patterns which are very important for your immune system. Make it a priority to reduce or eliminate stress in your job, family, or social environments until the management of your myeloma is well-controlled.

Clinical Trials

The following organizations offer free, searchable listings of cancer clinical trials. Other organizations including major cancer centers and drug manufacturers also offer such listings.

www.clinicaltrials.gov
The U.S. National Institutes of Health has developed ClinicalTrials.gov to provide patients, family members and members of the public current information about clinical research studies. ClinicalTrials.gov contains summary information about clinical trials being conducted throughout the United States and in many countries throughout the world. These data are provided to the National Library of Medicine by organizations and institutions that sponsor and implement the studies. ClinicalTrials.gov is updated daily, so check frequently for updated information.

www.centerwatch.com
As a pioneer in publishing clinical trials information, CenterWatch was the first Internet site to publish detailed information about active clinical trials that could be accessed by patients and their advocates. Today, they have one of the largest clinical trial databases actively seeking patients on the Internet.

www.emergingmed.com
EmergingMed’s Navigator service enables you to create a detailed profile to see if you match the eligibility requirements of more than 10,000 trials in the United States and Canada. Their Clinical Trial Specialists will work with you by telephone to make sure you get the information you need to make important decisions about clinical trial options. (877) 601-8601.

www.trialcheck.org
TrialCheck is an online search engine where people can find tailored information about cancer clinical trials that are enrolling patients at hospitals, cancer centers, and oncology practices in the U.S. and internationally.

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