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Introduction

Multiple myeloma is a bone marrow cancer. Despite periodic media attention, general public awareness about myeloma is low. The intent of this booklet is to provide basic information and suggestions about how to cope with this disease.

The International Myeloma Foundation (IMF) is committed to providing education and support for patients and families. This handbook provides a basic understanding of myeloma sufficient to allow patients to make informed decisions about treatment choices. The handbook is supplemental to the information given by the doctor. Caregivers, family, and friends may also find the information useful.

Although there is currently no cure for myeloma, it is an eminently treatable disease. Many patients go on to lead full lives for years, even decades, after diagnosis. With increasing research, the overall outlook for patients is improving steadily. Knowing more about the disease, and understanding what can be done to help, reduces anxieties and makes it easier to come to terms with the diagnosis.

Myeloma is a very individual disease. Myeloma is often slow moving, but can sometimes be more aggressive. While the doctor assesses each particular situation and recommends the best approach, the patient plays a central role in helping make these individual treatment decisions. It is important that patients and their families be well informed, ask questions, and give serious thought to alternative strategies or options.


What is myeloma?

Myeloma is literally an "oma," or tumor, involving the "myelo," or bloodproducing cells in the bone marrow. The cells that are affected are plasma cells (a type of white blood cell), which are our antibody- (immunoglobulin-) producing cells. A malignant or cancerous plasma cell is called a myeloma cell. Myeloma is called "multiple" since there are frequently multiple patches or areas in bone where tumors or lesions have developed. A single lesion is called a solitary plasmacytoma.

Myeloma affects the places where bone marrow is normally active in an adult. This marrow is in the hollow area within the bones of the spine, skull, and pelvic bones, the rib cage, and the areas around the shoulders and hips. The areas usually not affected are the extremities: that is the hands, feet, and lower arm/leg regions. This is very important since the function of these critical areas is usually fully retained.

Myeloma can be discovered at a precancerous stage (see Table 1). In some cases the myeloma cells build up very slowly in the bone marrow. The very earliest stage is called MGUS. This is not a cancer, but a condition called Monoclonal Gammopathy of Undetermined Significance. In MGUS, the myeloma cells constitute fewer than 10% of the bone marrow cells. The risk of transition from MGUS to active myeloma is very low: only a 1% chance each year of follow-up. Even if the myeloma cells are at a higher level of 10-30% of the total bone marrow, the growth rate can be very slow and represent indolent/smoldering or asymptomatic myeloma. Both MGUS and indolent myeloma can change very slowly over a period of years and do not require active treatment. It is very important to establish the correct diagnosis distinguishing MGUS and indolent myeloma from active or symptomatic myeloma, which does require treatment.

TABLE 1: DEFINITIONS OF MGUS AND MYELOMA
OLD NAME	NEW NAME	DEFINITION
MGUS (Monoclonal Gammopathy of Undetermined Significance)	MGUS (i.e., no change in name)	Monoclonal protein present. No underlying disease state.
SMOLDERING or INDOLENT MYELOMA	ASYMPTOMATIC MYELOMA	Higher level of disease than MGUS, but still no symptoms or organ damage.*
MYELOMA	SYMPTOMATIC MYELOMA	Monoclonal protein present, and One or more "CRAB" features of organ damage.*
*ORGAN DAMAGE CLASSIFIED AS "CRAB" C - calcium elevation (> 10 mg/L) R - renal dysfunction (creatinine > 2 mg/dL) A - anemia (hemoglobin < 10 gm/dL) B - bone disease (lytic lesions or osteoporosis) ONE OR MORE required for diagnosis of SYMPTOMATIC MYELOMA

Basic facts about myeloma

Although several things appear capable of causing or triggering myeloma, all of the details are not known. Things associated with an increased risk of myeloma and related diseases are toxic chemicals (for example, agricultural chemicals and Agent Orange used in Vietnam as well as a whole range of petrochemical compounds), radiation (including atomic radiation), and several viruses including human immunodeficiency virus (HIV), hepatitis viruses, human herpes virus 8 (HHV-8), and others. There is not a strong family tendency for myeloma; however, a few families do have an increased predisposition to the disease.

Myeloma occurs in adults. The average age of onset of myeloma is in one's early 60s. Only 5-10% of patients are under the age of 40 years. Myeloma occurs more commonly in men and in some racial groups, such as African-Americans.

There are approximately 20,000 new cases of myeloma in the U.S. each year. The incidence ranges from ~0.5-1/100,000 among Asians to as high as ~10-12/100,000 among African-American men. At any one time there are over 100,000 myeloma patients undergoing treatment for their disease in the U.S.


Why myeloma has to be treated

Myeloma, if left untreated, can cause bone damage, elevated blood calcium, low blood counts (especially anemia), predisposition to infection, and kidney damage. Because the bones of the spine are often affected and because myeloma proteins produced by myeloma cells can damage nerves, it is common to have spine and nerve problems that may require urgent attention.

In getting treatment for myeloma, it is important to distinguish between urgent problems such as bone damage, infection, kidney damage, or nerve pressure, which need immediate attention, versus overall planning to treat the disease. Sometimes urgent care cannot and should not be delayed. However, early consultation with a hematologist/oncologist familiar with myeloma is encouraged. For example, options of emergency surgery versus radiation therapy can be discussed. Also, making sure that all treatment options are kept open for the future is an important consideration.

Once urgent matters have been dealt with, overall plans can be discussed in more detail. Frequently there is time to seek a second opinion or consultation with an expert to be assured that all options are carefully reviewed. Even if plans seem to be clear, if there are any concerns, questions, or doubts, it is better to have these aired sooner rather than later. Having a mutually agreed-upon plan with your physician for ongoing treatment is tremendously important.


What causes the medical problems with myeloma

Healthy plasma cells produce immunoglobulins, which are complex proteins that we call "antibodies." Myeloma cells do not make functioning antibodies, but instead produce a clonal protein, or immunoglobulin, that is known as a "monoclonal protein".
All of the medical problems related to myeloma are caused by the build-up of myeloma cells (see Table 2). Unlike other types of cancer, myeloma can present patients with many strange complications because myeloma cells do not just produce tumors, they release many proteins and other chemicals into the local microenvironment of the bone marrow and directly into the blood stream.

• Local effects in the bone marrow. The effects in the bone marrow include a reduction in blood cell production and damage to the surrounding bone. The net results are the many common features of myeloma, such as anemia, predisposition to infection, bone pain, bone fractures, and elevated blood calcium
• Effects outside the bone marrow. The effects outside the bone marrow are mostly due to the monoclonal protein produced by the myeloma cells. As the myeloma cells build up in the bone marrow, the immunoglobulin or antibody protein that is specific to the myeloma is released into the blood circulation. This specific immunoglobulin protein or monoclonal protein produced by myeloma cells can cause tissue damage at distant sites; for example, kidney damage is not uncommon. The protein can interfere with blood clotting and/or circulation, and can potentially cause other organ or tissue damage.

Treatment for myeloma reduces tumor growth as well as these diverse effects from myeloma proteins and chemicals.

TABLE 2: MEDICAL PROBLEMS RELATED TO MYELOMA
EFFECTS OF INCREASED MYELOMA CELLS IN BONE MARROW	CAUSE	IMPACT ON PATIENT
Anemia (A*)	Decrease in number and activity of red blood cell-producing cells.	Fatigue Weakness
High protein level (in blood and/or urine)	Abnormal or monoclonal protein produced by the myeloma cells is released into the bloodstream and can pass into the urine (where it is called Bence Jones protein).	Sluggish circulation Possible renal or kidney damage (R*)
Bone Damage (B*): Thinning (osteoporosis) or Areas of more severe damage cause lytic lesions, fracture or collapse of a vertebra	The myeloma cells activate osteoclast cells, which destroy bone, and block osteoblast cells, which normally repair damaged bone.	Bone pain Bone swelling Fracture or collapse of a bone
High blood calcium (C*)	Release of calcium from damaged bone into bloodstream	Mental confusion Dehydration Constipation Fatigue Weakness Renal or kidney damage (R*)
Reduced normal immune system function against infection	The myeloma cells block production of normal antibodies against infection	Susceptibility to infection Delayed recovery from infection
*CRAB criteria: C Calcium; R Renal/kidney; A Anemia; B Bone

Different types of myeloma

There are different types and subtypes of myeloma. These are based on the type of immunoglobulin (protein) produced by the myeloma cell. Normally, the various immunoglobulins have different functions in the body. Each immunoglobulin protein is made up of two heavy chains and two light chains. (See Figure 1). There are five types of heavy protein chains: G, A, D, E, and M. There are two types of light protein chains: kappa (κ) and lambda (λ or L). The typing of myeloma (done with a test called "immunofixation" [IFE]) identifies both the heavy and light chains. Most myeloma patients, about 65%, have IgG (iG) type myeloma with κ or λ light chains. The next most common type is 19A (iA) type myeloma, also with either κ or λ light chains. (See Table 3). IgM, IgD, and IgE myelomas are quite rare.

Approximately 30% of patients produce light chains in the urine (such as kappa light chains) as well as heavy and light chains (such as IgG kappa) in the blood. In about 10% of patients, the myeloma cells produce only light chains and no heavy chains. This is called "light chain" or "Bence Jones" myeloma. Rarely (in about 1-2% of patients) the myeloma cells produce very little or no monoclonal protein of any type. This is called "non-secretory" myeloma. However, the freelite™ test (serum free light chain assay) can detect minute amounts of light chains in the blood of most of these patients.

TABLE 3: TYPES OF MYELOMA
HEAVY CHAIN*	LIGHT CHAIN**	MYELOMA TYPE
IgG: (immunoglobulin G)	kappa (κ) or lambda (λ or L)	IgGκ or IgGλ immunoglobulin G with kappa or lambda light chains
IgA: (immunoglobulin A)	kappa (κ) or lambda (λ or L)	IgAκ or IgAλ immunoglobulin A with kappa or lambda light chains
* Rarer types are IgD, IgE and IgM ** There are only 2 light chain types

There are subtle differences in the behaviors of different types of myeloma. IgG myeloma has the usual features of myeloma. The 19A type can sometimes be characterized by tumors outside of the bone. The IgD type can be accompanied by plasma-cell leukemia and more frequently causes kidney damage. The light chain or Bence Jones myelomas are the most likely to cause kidney damage and/or lead to deposits of light chains in the kidneys and/or on nerves or other organs. Depending upon the characteristics of the light chain deposits, this condition is called either amyloid or light chain deposition.


Staging of myeloma

When myeloma is diagnosed, the amount of myeloma in the body varies from patient to patient. This is called the stage of myeloma. The previously most commonly used staging system is shown in Table 4, and shows the correlation between the extent of the myeloma and the damage caused, such as bone disease or anemia. The outlook is better when treatment is started early and bone disease or other complications can be prevented. The most current staging system is shown in Table 5, and is the result of the collaboration of more than twenty research institutions world-wide.

TABLE 4: THE DURIE AND SALMON STAGING SYSTEM
STAGE	CRITERIA	MEASURED MYELOMA CELL MASS (myeloma cells in billions/m²)*
STAGE I (low cell mass)	All of the following: Hemoglobin value > 10 g/dL Serum calcium value normal or < 10.5mg/dL Bone x-ray, normal bone structure (scale 0), or solitary bone plasmacytoma only Low M-component production rates IgG value < 5g/dL; IgA value < 3g/dL Urine light chain M-component on electrophoresis < 4g/24h	600 billion*
STAGE II (intermediate cell mass)	Fitting neither Stage I nor Stage III	600 to 1,200 billion* *myeloma cells in whole body
STAGE III (high cell mass)	One or more of the following: Hemoglobin value < 8.5g/dL Serum calcium value > 12mg/dL Advanced lytic bone lesions (scale 3) High M-component production rates IgG value > 7g/dL IgA value > 5g/dL Bence Jones protein > 12g/24h	> 1,200 billion*
SUBCLASSIFICATION (either A or B)	A: relatively normal renal function (serum creatinine value) < 2.0 mg/dL B: abnormal renal function (serum creatinine value) > 2.0 mg/dL Examples: Stage IA (low cell mass with normal renal function) Stage IIIB (high cell mass with abnormal renal function)

TABLE 5: INTERNATIONAL STAGING SYSTEM (ISS) Staging for Multiple Myeloma
STAGE	VALUES
STAGE 1	β2M < 3.5 ALB ≥ 3.5
STAGE 2	β2M < 3.5 ALB < 3.5 or β2M 3.5-5.5
STAGE 3	β2M > 5.5
Note: β2M = Serum β2 microglobulin in mg/L ALB = Serum albumin in g/dL

Several tests (assessments of so-called prognostic factors, from the Greek words that mean "knowing ahead") can be used to assess how aggressive the myeloma is in a given patient. In general, higher or abnormal test results indicate more active myeloma, and possibly, less likelihood of having a long response with treatment (Table 6).

TABLE 6: PROGNOSTIC FACTORS
TEST	SIGNIFICANCE
Serum β2 microglobulin (S β2M)	The higher the level the more advanced the stage
Serum Albumin (S Alb)	The lower the level the higher the stage
C-reative protein (CRP)	Increased with active disease
Serum LDH (lactate dehydrogenase)	Increased with active disease
Abnormal chromosomes on bone marrow cytogenetics and FISH (Fluorescent In Situ Hybridization)	Several chromosome deletions or translocations; can be associated with shorter duration of remission

Testing at diagnosis

Table 7 summarizes the typical testing required at the time of diagnosis (baseline testing).

TABLE 7: BASELINE TESTING
TEST	PURPOSE
Bone marrow biopsy Special testing is done to assess prognosis (e.g., chromosomes, immune typing, staining for amyloid)	This is the single most critical test to determine the percentage of myeloma cells in the bone marrow. In Stage I disease or for a solitary plasmacytoma, direct biopsy of the tumor mass is performed. Chromosome analysis (cytogenetic testing) can reveal good or poor chromosome features using direct and/or FISH analysis.
Blood Testing 1. Complete blood count (CBC) 2. Chemistry panel 3. Special protein testing Serum protein electrophoresis (SPEP) Immunofixation FREELITE® test	To assess presence/severity of anemia (low hemoglobin) To assess for low white cell count To assess for low blood platelet count Particularly important to assess kidney function (creatinine and BUN), albumin, calcium level, and LDH This shows the presence of the monoclonal myeloma protein. The amount of the abnormal myeloma protein. Shows the type of myeloma protein [i.e., heavy chain (G, A, D or E), light chain, kappa (κ), lambda (λ)]. Can be used to measure the amount of free kappa or lambda if no SPEP or UPEP abnormality discovered.
Urine Testing Special protein testing similar to serum above: Urine Protein Electophoresis (UPEP) Immunofixation	Shows the presence, amount, and type of abnormal myeloma protein in urine.
Bone Testing X-Rays MRI CT Scan Nuclear Medicine Scans FDG/PET Scan Bone Density Testing	To assess the presence, severity, and location of any areas of bone damage. X-rays are still the gold standard in searching for myeloma bone damage. A full skeletal survey for myeloma using a series of X-rays is needed to show loss or thinning of bone (osteoporosis or osteopenia caused by myeloma bone destruction), lytic lesions, and/or any fracture or collapse of bone. Used when X-rays are negative and/or for more detailed testing of particular areas such as spine and/or brain. Can reveal the presence and distribution of disease in the bone marrow when X-rays show no bone damage. Can also reveal disease outside of bone, which may be pressing on nerves and/or spinal cord. Used when X-rays are negative and/or for more detailed testing of particular areas. Especially useful for detailed evaluation of small areas of possible bone damage or nerve pressure. Routine bone scans used for other cancers. Not useful in myeloma and should not be performed. A much more sensitive Whole Body scanning technique. Useful for disease monitoring, especially for non-secretory disease Helpful to assess the severity of diffuse bone loss in myeloma and to measure the serial improvement with bisphosphonate therapy.

Treatment of myeloma

Deciding about treatment is the most important initial decision. As already emphasized, baseline testing, staging, and prognostic classification are essential. Treatment is recommended for active or symptomatic myeloma. The urgency of treatment depends upon the exact problems faced by an individual patient.

TABLE 8: GOALS OF MYELOMA TREATMENT
TYPE OF TREATMENT	OBJECTIVE	EXAMPLES	TIME TO DECIDE
Stabilizing	Countering the lifethreatening disruptions to body chemistry and the immune system	Plasmapheresis to thin the blood and avoid stroke Hemodialysis when kidney function is impaired Drugs to reduce hypercalcemia (may include chemotherapy	Hours to Days
Palliative	Relieving discomfort and increasing the patient's ability to function	Radiation to stop bone destruction Erythropoietin to relieve anemia Orthopedic surgery to repair and/or strengthen bone	Days to Months
Remission-Inducing	Improving symptoms, slowing or arresting the course of the disease	Therapy to kill malignant cells throughout the body Radiation to kill malignant cells at a tumor site	Weeks to Months
Curative	Permanent remission*	Bone marrow transplants as a means of delivering high-dose chemotherapy	Weeks to Months
* Although never achieved and confirmed, permanent remission remains the objective of many experimental treatments.

Initial or frontline therapy

It is important for patients to set aside plenty of time to discuss the options with their hematologist or hematologist/oncologist. In addition to the baseline test results, one must consider:

• How much impact does the myeloma have on day-to-day functioning?
• Will the patient be able to work? Are plans in place to be off work as needed to undertake treatment?
• How old is the patient? Are there any other medical problems?
• Can the patient tolerate potential treatments?
• Is high-dose chemotherapy with stem cell transplant an option?
• How well and how rapidly one responds to treatment varies from patient to patient.
• All treatment decisions do not need to be made on "Day 1."
• It is generally best to keep the door open for stem cell transplantation if you feel it can be a future option for you.
• Although frontline clinical trials are available, you have to be completely comfortable that you will be randomly assigned to one treatment versus another. You may become "locked in" to future randomization and treatments. Make sure you understand the full scope of the protocol.
• If one treatment does not work, this does not mean that another treatment cannot work extremely well and give an excellent remission.

TABLE 9A: 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
Dexamethasone* alone	Pulse dexamethasone alone provides a substantial percentage of the benefit of the full VAD	Dexamethasone on an intensive schedule can be poorly tolerated
R or RD or Rd (RevloDex)* (Revlimid® alone, with Dexamethasone, or Revlimid® with lowdose Dexamethasone)	Excellent response rates Oral Generally well-tolerated and increasingly popular	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.

TABLE 9B: 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 our website at www.myeloma.org.

Supportive care

Treatments are available to alleviate the physical and emotional impact of the disease. Early use of supportive care measures is just as important as initiating frontline therapy.

TABLE 10: SUPPORTIVE CARE
SYMPTOM	TREATMENT	COMMENTS
Fatigue and weakness due to anemia	Blood transfusion (packed red blood cells: leukoreduced, virus screened) if anemia severe Erythropoietin if anemia mild to moderate	The treatments are simple, usually highly beneficial, and improve feelings of well being.
Bone Pain	Bisphosphonate (e.g., Aredia® 90mg IV over 2-4 hrs monthly; Zometa® 4 mg IV over 15-45 minutes monthly) Pain medication as needed (e.g., Tylenol®, oral morphine derivatives, Fentanyl® "Pain Patch")	Relief of bone pain is important in itself and improves physical activity, which in turn promotes bone strength and healing and improves emotional well-being. Potential damage to kidneys and jaws, though rare, can result from chronic bisphosphonate therapy. Awareness is the key to prevention.
Fever and/or evidence of infection	Appropriate antibiotics Neupogen® if necessary to boost low white blood cell count Intravenous gamma globulin for severe infections Tests as needed to diagnose the exact type of infection (except for dangerous biopsies/cultures) should be performed.	Although antibiotics should be selected and used with care, it is extremely important that infections be brought under control promptly. Having an antibiotic on hand for emergency use (especially if traveling) is recommended.

Beyond the management of specific symptoms, a whole range of supportive measures is critically important:

• Physical activity - Patients should check with their physicians to clarify if full physical activity is feasible or if adjustments need to be made because of bone disease and particular areas of bone damage. Usually, some physical activity such as planned walking or swimming, flexibility and strengthening exercises, and/or a personalized yoga program, can be set up.
• Diet - No specific diet has been developed for myeloma patients. This is an area of ongoing research. In general, "healthy diet" recommendations from other disease settings such as cardiac disease and cancer in general (e.g., breast cancer) can be utilized. Caution should be used in two areas:
• Vitamin C - High doses (i.e., > 1000 rug/day) may be counter-productive in myeloma and increase the risk of kidney damage.
• Herbal and vitamin supplements - Talk to your doctor or oncology center pharmacist about using supplements along with chemotherapy or other drug treatment. Drug interactions can create medical problems. Most pharmacies have systems which identify potential interactions with supplements in addition to medications.
• Mental health - Your mental health is critical as you move forward with planned treatment. Make sure you are comfortable with the treatment planned. Schedule an appointment with a mental health professional if you believe that you might be depressed, or if others are concerned that you might be depressed.
• Regular sleep - This is very important for your immune system.
• Make adjustments - As much as possible, reduce or eliminate stress in job, family, or social situations. Management of the myeloma is the top priority until remission and/or a stable situation has been achieved.

If frontline therapy is not working

There are numerous treatment options beyond the scope of this introductory handbook. Emerging new therapies are increasingly available and can provide major benefit.

Please visit the IMF website at www.myeloma.org for more information and regular updates or call the IMF at 800-452-CURE (2873).


Questions to ask your doctor

Treatment decisions are critically important to the survival and quality of life of the myeloma patient. To make an informed decision, the patient needs to have the facts. Some patients want to discuss all aspects of their situation, treatment, and prognosis. Others just want to know what to do next. Most doctors are sensitive to this and will vary their approach based on what they perceive to be the patient's wishes.

We encourage patients to be explicit about how deeply they want to get into the details of the treatment decision. And, no matter how comfortable the patient feels with a doctor, it is generally good practice to get more than one opinion before proceeding.

1. Get a complete description of the treatment program:

• What exactly is the treatment?
• What are the objectives of the treatment?
• Over what period will the treatment be given?
• What is involved? How often must the patient visit a medical facility? Is hospitalization required or a probability? What is the likely impact on the patient's ability to function (i.e., work and play)? How do people feel before, during, and after treatment? How do they look? What are typical recovery time frames?
• What follow-up or maintenance programs are required?
• What will the treatment program cost? Will it be covered by health insurance?

2. How well has this treatment worked for others in similar situations?
   Effectiveness is measured in many different ways:

• How much experience is there with the treatment? How many patients have received it? How long have those patients been followed after the treatment?
• What are the odds of achieving a complete or partial remission? Which factors suggest better or worse odds?
• How long have the patients' remissions lasted? Which factors correlate to long or to short remissions?
• What would be the options in the event of a relapse? (These options may change in the interim.)
• What are reasonable expectations for relieving symptoms such as bone pain, pathological fractures, anemia, fatigue, hypercalcemia? What are the factors that predict how well these treatments will work for symptoms?
• How long have people who have received the treatment survived? For newer treatments, how many of the original group of patients are still alive?

3. Like most cancer treatments, myeloma treatments generally use strong drugs and other measures aimed at destroying malignant cells and/or rebalancing body chemistry. Typically, there are side effects. Some manifest themselves during treatment. Others may show up well after the treatment is completed.

• What side effects have been observed in patients receiving the treatment? When do they typically occur? In what percentage of patients do they occur? How serious are the side effects? Are they life threatening? Are they painful? Are they permanent? How long do they last?
• Are there treatments for the side effects? Do the treatments for the side effects have side effects?

4. There are always alternatives. You need to ask all of these questions for each of the alternatives:

• What are the alternatives to the recommended treatment?
• What are the relative pros and cons of the alternatives?
• What are the pros and cons of the alternative treatments vs. no treatment?

Because the disease is rare, there are a limited number of practitioners and centers specializing in myeloma. It is very common for a myeloma patient to seek a second opinion from a specialist at a research center while continuing to rely on a local referring physician to administer and monitor treatment.

Making good decisions about treatment requires resourcefulness, careful questioning, serious thought, and courage. But, most of all, it requires that the patient and his/her support group take charge of the process.

Because there is no known cure, because there are no guarantees, because every individual is different, the ultimate decision depends on the preferences and priorities of the patient.