Untitled

To discuss any of the information contained in this guide, or further assistance, please call the Myeloma Support Line on 1800 MYELOMA (1800 693 566) A Myeloma Support Nurse will answer your call in confidence Publication date: August 2014 toll free: 1300 632 100
myeloma support line: 1800 693 566
Myeloma Australia PO Box 5017, Burnley, Vic 3121 Myeloma Australia is a trading name of Myeloma Foundation of Australia Inc.
This publication is supported by an educational grant by Janssen.
All content in this publication has been independently prepared by Myeloma Australia Myeloma – A Comprehensive Guide
This guide is written for patients who have been diagnosed with myeloma. It will also be
helpful for their families, carers and friends. It provides comprehensive information on
myeloma and its treatment and management. The purpose of this guide is to promote a
better understanding of the disease, which will enable informed decisions about care and
treatment options. Being informed is a key step in learning to manage and cope. Some
of the more unusual or technical words appear in bold the first time they are used and
are described in the glossary of medical terms at the back of the guide. We recognise that
not everyone requires such a comprehensive guide, particularly when first diagnosed with
myeloma. A simpler myeloma guide can be found at www.cancercouncil.com.au.
Myeloma Australia is a national non profit organisation dedicated to providing information
and support for those affected by myeloma. Founded in Victoria in 1998 by three families
personally touched by myeloma, the organisation has grown to become a significant
provider of services and support for the myeloma community.
Myeloma Australia: • raises awareness of myeloma through workshops, seminars, website, Facebook, Twitter • provides funding for research projects • advocates to state and federal government for support regarding access to new therapies, provision of specialist nurses, changes to the PBS for cancer drugs • provides education, information and support to patients and carers through its specialist myeloma support nurses.
To talk to someone about any aspect of myeloma, its treatment and management call the Myeloma Australia Support Line on Freecall 1800 MYELOMA (1800 693 566). The Support line is available 9am to 5pm (AEST) Monday to Friday and a myeloma support nurse will answer the call in confidence.
2014 update: Tracy King, Myeloma Nurse Consultant Royal Prince Alfred Hospital, Clinical Research Fellow, Cancer Nursing Research Unit, The University of Sydney and Hayley King, Myeloma Support Nurse Manager, Myeloma Australia.
Author: 2010,2012 Tracy King, Myeloma Nurse Consultant Royal Prince Alfred Hospital, Clinical Research Fellow, Cancer Nursing Research Unit, The University of Sydney.
Myeloma UK whose 2006 patient guide formed the basis of the original publication.
We would also like to thank reviewers of this guide: Prof Miles Prince AM (Consultant Haematologist and Director, Centre for Blood Cell Therapies Peter MacCallum Cancer Centre, Melbourne) and Helen Chapman (Editor and consumer representative). ABN: 30 476 390 368Publication date: November 2010.
Updated: August 2014Next review: August 2016 Printed by Eastern Press Pty Ltd www.epress.com.au Website: www.myeloma.org.auEmail: [email protected] Support Line 1800 MYELOMA (1800 693 566)Admin: 1300 632 100Myeloma AustraliaPO Box 5017, Burnley, VIC 3121 Contents
P4 Introduction
P5
What are the different types of myeloma? What are the symptoms of myeloma? How is myeloma diagnosed? What is the treatment for myeloma? What treatment will be offered first? Conventional chemotherapy based combinations P27 Corticosteroids Immunomodulatory drugs (IMiDs) P31 Lenalidomide Combinations of treatments High dose therapy and Autologous Stem Cell Transplantation (AuSCT) What are the treatments for symptoms and comlications due to myeloma? P52 PainP53 FatigueP54 Kidney Anaemia and infections How is myeloma treated when it becomes active again? How does a patient know if the treatment has worked? New treatments and clinical studies Living with myeloma Communication with the medical team Self help checklist Further information and useful organisations Medical terms explained P86 AppendicesP93 NotesP96 Contact Disclaimer
While the advice and information in this guide is believed to be true and accurate at the time of publication,
neither the authors, neither reviewers, nor the publishers accept any legal responsibility for the content. It
is strongly recommended that advice is sort directly from medical professionals for the correct response for
individual circumstances.
Receiving a diagnosis of myeloma can naturally be bewildering. Many may never have heard of the condition. Myeloma is a complex disease and this guide is designed to help people understand the nature of the disease, the available treatment options, signs and symptoms and how to manage with the condition.
It is important to remember that myeloma is often a slowly progressing disease and there are now many treatment options. With improvements in treatment, people are increasingly living well with myeloma for years.
We hope everyone finds this guide informative and helpful as a reference at various times throughout diagnosis and treatment. There is a page to record useful contact numbers and a notes page to write questions for the medical team.
It is beyond the scope of any booklet to include everything there is to know and understand about myeloma. We have therefore made note within the booklet to further reading and information resources available by Myeloma Australia and other organisations, for those interested in learning more. Myeloma Australia understands specifically about myeloma and has resources, information and support to assist you at any time. The myeloma support nurses are there to speak to patients, family members, carers and friends. Call 1800 MYELOMA (1800 693 566) Monday to Friday 9am – 5pm or visit the website for many more resources such as frequently asked questions answered by haematologists: www.myeloma.org.au.
What is Myeloma?
Myeloma, also known as multiple myeloma, is a type of bone marrow cancer
arising from plasma cells, which are normally found in the bone marrow.
Plasma cells form part of our immune system.
Normal plasma cells produce antibodies (also called immunoglobulins) to
help fight infection. In myeloma, the abnormal plasma cells release only one
type of antibody known as the monoclonal(M) protein or paraprotein, which
has no useful function. It is often through the measurement of this paraprotein
that myeloma is diagnosed and monitored.
Bone marrow is the ‘spongy' material found in the centre of larger bones in the
body (see Figure 1). As well as being home to plasma cells, the bone marrow
is the centre of blood cell production (red blood cells, white blood cells
and platelets).
Figure 1. Bone marrow diagram In myeloma, the DNA of a plasma cell is damaged causing it to become
malignant or cancerous. These abnormal plasma cells are known as myeloma
cells. Unlike many cancers, myeloma does not usually exist as a lump or tumour.
Instead, the myeloma cells usually divide and expand within the bone marrow.
Myeloma affects multiple places in the body (hence multiple myeloma) where bone marrow is normally active in an adult, i.e. within the bones of the spine, skull, pelvis, the rib cage, 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.
Most of the medical problems related to myeloma are caused by the build up of myeloma cells in the bone marrow and the presence of the paraprotein in the blood or in the urine.
Common problems are bone pain, bone fractures, tiredness (due to anaemia),
frequent or recurrent infections (such as bacterial pneumonia, urinary tract
infections and shingles), kidney damage, and elevated calcium in the blood
(hypercalcaemia).
A small percentage of people go on to develop myeloma after having been
diagnosed with a benign (non malignant) condition called MGUS which
stands for Monoclonal Gammopathy of Undetermined Significance. This term
describes the condition of the raised abnormal protein seen in myeloma (the
paraprotein), but where there are no other features of the disease (less than
10% plasma cells in bone marrow and no evidence of bone disease).
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, their rate of growth can be very slow and represents asymptomatic
(also known as indolent or smouldering) myeloma.
Both these conditions 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 asymptomatic myeloma from active or symptomatic myeloma, which does require treatment.
Treatments for myeloma can be very effective at halting its progress, controlling the symptoms, and improving quality of life, but they are not able to cure it. Even after successful treatment, regular monitoring is needed for when the myeloma returns (relapse). If the myeloma is under control people usually return to a good state of health which can last from months to years. The outlook for myeloma is improving with many new developments in the treatment and management having had a significant impact on improved outcomes. Research is ongoing to develop new treatments and to use existing treatments in a better, more effective way. Many of the current and new developments are discussed in this guide.
Basic Facts:
• There are approximately 1,400 new cases of myeloma per year in Australia
• About 5,000 people are living with myeloma at any one time • Slightly more males than females will have myeloma • Myeloma accounts for 15% of blood cancers and 1% of cancers generally • Median age of onset is 70 and only 5-10% of patients are under 50 Further information about living with myeloma can be obtained by accessing one or more of the many services offered by Myeloma Australia. In the first instance, contact one of the myeloma support nurses on 1800 MYELOMA (693 566)
What are the different types of myeloma?
Myeloma is often described as being a very individual disease; both in terms of the way those affected experience complications and in the way they respond to treatment, all of which can vary greatly. Some of this variation is due to the different types and subtypes of myeloma.
Different types and sub types of myeloma are based on the type of immunoglobulin (paraprotein) produced by the myeloma cell.
Each immunoglobulin is made up of a specific structure containing two
principal components, heavy chains of which there are two, and light chains
of which there are also two (see Figure 2).
There are five possible types of
heavy chain component denoted
by the letters G, A, D, E and M, and
there are two possible types of
light chain component denoted
by the Greek letters, Kappa (ڒ) and
Lambda (ڔ).
Each individual immunoglobulin (Ig for short), can have only one of the five possible heavy chain types and only one of the two possible light chain types.
Most people with myeloma, about 65%, have what is called IgG type myeloma. That is immunoglobulin type G (one of the five possible Figure 2. Immunoglobulin diagram heavy chains), with either the kappa or lambda light chain component.
The next most common type is IgA myeloma also with either kappa or lambda light chains. IgM, IgD and IgE type myeloma are all quite rare.
At the same time as producing one whole immunoglobulin structure, approximately 30% of patients will also produce light chains (such as kappa light chains) on their own, which are detectable in the urine rather than in the blood.
In about 20% of patients, the myeloma cells produce light chains only (no heavy
chains at all). This is called light chain or Bence Jones myeloma.
More rarely, in about 1-2% of cases, the myeloma cells produce very little or no immunoglobulin of any type. This is known as non secretory myeloma making diagnosis and monitoring very difficult. However, a test called the Freelite™ test is able to detect minute amounts of light chains in the blood in most of the patients traditionally labelled as having non secretory myeloma, therefore making diagnosis and monitoring easier.
The light chain or Bence Jones myelomas are the types most likely to cause
kidney damage. If light chains deposit in the kidneys, nerves or other organs
it can result in a conditions known as AL amyloidosis or light chain
deposition disease.
Regular measurements of the paraprotein are taken to help confirm a diagnosis and determine the subtype of myeloma. Measurements are also taken during the course of the disease to help determine the response to any given therapy and for periodic restaging of the disease. What Causes Myeloma?
Although there has been a large amount of research to investigate the potential triggers of myeloma, nothing has been proven to date.
Exposure to certain chemicals, radiation, viruses and a weakened immune system are thought to be potential causal or trigger factors. It is likely that myeloma develops when a susceptible individual has been exposed to one or more of these factors. Because it is more common to develop myeloma later in life, it is thought that susceptibility may increase with the ageing process and the associated reduction in immune function, or that myeloma may result from a lifelong accumulation of toxic insults or antigenic challenges.
There is a rare tendency for myeloma to occur in families, but the likelihood is very low, and no tests are currently available for screening of this. Even when myeloma occurs more than once within a family, this may be due to a common exposure to environmental factors, rather than it being hereditary.
What are the symptoms of myeloma?
Myeloma can cause a range of symptoms because of its effect on the bones, bone marrow and kidneys. In some people there are no symptoms at diagnosis or in the early stages. When present, symptoms may be vague and similar to those of other conditions. Some of the more common symptoms are: • Bone pain or a broken bone that has not been caused by obvious injury • Fatigue and general weakness • Frequent or prolonged infections • Loss of appetite and weight loss • Kidney impairment • Increased thirst, confusion and nausea – caused by a high level of calcium in More about managing these symptoms is covered later in this guide. How is myeloma diagnosed?
Common tests and investigations
In order to diagnose myeloma, several tests and investigations are needed. This is often a difficult and uncertain time for those affected by myeloma and their families. Tests and investigations are carried out for three main reasons: • To establish a diagnosis and extent of the disease • To help determine a treatment plan and monitor progress • To detect complications of the disease Myeloma is a very individual disease and test results may vary from patient to patient. It is not enough just to make a diagnosis of myeloma; it is critical to have an accurate picture of the disease in each person affected before an appropriate treatment plan can be developed.
As well as being important in diagnosing myeloma, changes in the level of paraprotein (in the blood and/or urine) are usually a fairly good indicator of changes in the activity of the myeloma. For this reason, paraprotein measurements are done regularly at intervals determined by the doctor (e.g. monthly or 3 monthly) to see how well the treatment is working and to check that the myeloma is remaining stable during periods between treatments. If no paraprotein is detectable after treatment it is considered a complete response (CR) has occurred. If the paraprotein has fallen and is still detectable and stable after treatment it is considered a partial response (PR). A stable, low level of paraprotein maintained over a period of time is often described as plateau phase. The term ‘plateau phase' is used because a graph of the paraprotein results appears flat like a plateau. Both the level and duration of response are important when measuring how successful treatment has been. Further information on measuring response to treatment can be found in the ‘Treatment' section of this guide. (see Table 6 p60 response criteria).
In about 20% of patients with myeloma, the abnormal paraprotein is detected in the urine where it is known as Bence Jones protein. A test called a 24hr urine collection may be used to measure the Bence Jones protein. Paraprotein can be measured by a simple blood or urine test in the following ways, depending on the type of myeloma: Blood tests:
• Serum protein electrophoresis (SPEP)
• Immunofixation electrophoresis (IFE) • Immunoelectrophoresis (IEP) • Serum Free Light Chain (SFLC)
Urine test:
• 24 hr urine collection for Bence Jones Protein X-rays of skeleton (skeletal survey)
Because myeloma can thin or erode the bones, one of the first investigations
performed is often a skeletal survey. This is a series of whole body X-rays used
to detect any bone damage. X-rays can also be used to help detect new bone
damage. Areas of bone damage show up on X-ray film as black shaded areas
and are known as ‘lytic lesions'.
Other scanning techniques
Sometimes an even clearer picture of the bone is needed using MRI (Magnetic
Resonance Imaging) or CT (Computerised Tomography) scans. MRI scans can
sometimes reveal the presence and distribution of myeloma in the bone and
outside the bone, while X-rays do not. CT scans provide more detail and can
identify areas of bone damage that may not show up on X-ray. A sestamibi
scan is a scanning technique using an injection of a radiolabelled isotope to
help detect myeloma deposits that may not be detected by other imaging
techniques. PET (Positron Emission Tomography) scan is rarely used for
myeloma assessment but can be helpful in some instances.
Bone Marrow Aspirate and Trephine Biopsy (BMAT)
This involves putting a needle into bone (usually the pelvic bone) to get a small sample of the bone marrow (sometimes called an aspirate), and is done under a local anaesthetic. This sample is then examined to count the percentage of plasma cells present in the bone marrow: normal bone marrow has fewer than 5% plasma cells; bone marrow in patients with myeloma may have between 10% and 90% plasma cells. This test may also be done at the beginning and end of each course of treatment. A better indication of the number of plasma cells is gained by doing a ‘trephine biopsy' which means taking a small core of bone along with the marrow inside.
Together with blood and / or urine sampling these tests help to give a more comprehensive picture of response to treatment. Analysis of the chromosomes (the structures that carry genetic information in
cells) found in the bone marrow samples can reveal good or poor chromosomal
features. During mutation, chromosomes can be gained (additional), be left
out (deletion) or break off and reattach elsewhere (translocation). Cytogenetic
results may be useful to guide treatment choices in those with high risk disease.
Chromosomal abnormalities that seem to be related to a higher risk myeloma
are termed t(4;14), t(14;16), t(14:20);del 17p and 1q21 amplification.
Researchers are currently exploring the relationship between different cytogenetic abnormalities and treatment outcomes. Full blood count
Throughout treatment, regular blood samples are taken. As has already been mentioned, blood samples are used to measure the level of paraprotein present in the blood. In addition, part of every sample is normally used to count the make up of some of the important cells in blood; the red blood cells, which transport oxygen; white blood cells, which help fight infection; and platelets, which help the blood to clot.
These cell counts are important because: • The white cell count indicates the risk of infection • The haemoglobin level (red cell count) detects anaemia • The number of platelets indicates the risk of bleeding or bruising more easily Kidney function can be affected by certain unique features associated with myeloma and also from the side effects of some treatments.
Blood tests are also used to help measure levels of urea and creatinine, which
are waste products that are normally filtered out by the kidney. High levels of urea and creatinine indicate poor kidney function.
Calcium is a mineral normally found in the bone. In patients with active bone disease due to myeloma, calcium is released from the bone into the blood stream, which can lead to higher levels of calcium in the blood (hypercalcaemia).
Albumin is a type of protein that normally makes up most of the protein found
in the blood, but in myeloma, hormones (or cytokines) produced by the
myeloma (mainly interleukin 6; IL 6) can suppress albumin production.
Beta 2 microglobulin (ß2M)
ß M is a molecule that sits on the cell surface of lymphocytes. Plasma cells
are a type of lymphocyte and myeloma cells express ß M on their surface. ß M is one of the most important indicators of both the amount and activity of the myeloma and therefore is crucial measurement in staging of the disease. LABTESTONLINE is a useful website resource to search for up to date information on laboratory tests and how they are used.
The appendix at the back of this guide includes a list of potential tests as well as some of the normal values Completion of a wide range of tests gives a clear and in depth picture of the specific characteristics of an individual's myeloma. With this information, the myeloma can be staged.
Staging indicates the amount of myeloma and therefore reflects the expected outlook for individual patients. The current International Staging System (ISS) for myeloma takes into account important factors such as ß M and albumin. Both these factors can be assessed by a simple blood test. International Staging System (ISS)
Serum albumin ≥35g/L ß M of < 3.5mg/L ß M <3.5mg/L and albumin <35g/L or ß M 3.5 – 5.5mg/L Stage III
Serum ß M of ≥5.5mg/L To help identify a person with myeloma that requires treatment, doctors often
use criteria summarised by the acronym ‘CRAB'.
Calcium elevation Renal (kidney) insufficiency/failure Bone abnormalities/disease (lytic lesions or bone loss) The CRAB criteria helps doctors determine if the myeloma is having an adverse
affect on the body and therefore decide the optimal time to start treatment.
The term Myeloma Related Events (MRE) or Related Organ Tissue Injury
(ROTI) is also used and refers to a very similar set of clinical features.
Note that while staging myeloma tells doctors how advanced the myeloma is, it does not predict the outcome of treatment. Even with advanced myeloma, successful treatment approaches are available. What is the treatment for myeloma?
Although myeloma remains an incurable disease, outcomes have improved
significantly, owing to the introduction of improved treatment options. Firstly,
the use of high dose therapy and autologous stem cell transplant (AuSCT)
in the late 1990's, then novel therapeutic agents in particular thalidomide
(Thalomid®), bortezomib (Velcade®) and lenalidomide (Revlimid®). This increase
in range of treatment options means there are an increasing variety of different
treatment combinations. The choice of best treatment will be tailored to each
individual and what may suit one person with myeloma may not be the best
option for another.
The likely course of the disease in those with myeloma is one of active treatment followed by periods of remission or stable disease where no treatment is required. During this time the haematologist / oncologist will be actively monitoring the blood and general health for signs of the myeloma returning or becoming more active. It is likely that a range of different treatment types will be used over time. The next few sections look at some important points in making treatment decisions and provide a brief overview of the range of treatments available to treat both the underlying problem and the complications and symptoms due to myeloma.
Choosing treatment for myeloma is not a simple decision as no one treatment has been identified as being the best, and all patients are different. The advantages, disadvantages and side effects arising from available treatments are often quite different. For this reason, being involved in deciding which treatment is best suited is very important. Generally, treatment options will take account of: • General health (for example, kidney function) • Personal circumstances and lifestyle • Priorities and preferences • The nature of the disease • Level of complications or side effects • Any previous treatments or illnesses • Results and response to any previous treatment received Making an informed decision
Making an informed decision is important and as much time should be taken as needed. However, in some situations there may be an urgent need to start treatment, for example if there is significant kidney damage. To get a better understanding of myeloma and the treatment options available it is a good idea to read credible resources. Information is available from doctors, nurses, Myeloma Australia, other support organisations such as the Cancer Council and the Leukaemia Foundation, and the Internet (a list of reliable websites is provided on page 72).
Listing the pros and cons of each option is a good way to help decide the best treatment. Talking things over with family, friends or other patients can help clarify and gain perspective.
Decisions should take into account personal priorities and lifestyle. Each treatment choice will have benefits and difficulties including potential side effects. It is important to ensure that there is an open discussion with the treating doctor and that each party agrees with the plan. The way cancer services are currently organised in Australia means that each hospital should involve a range of healthcare professionals working together as a team, known as a multidisciplinary team. Treatment is likely to have been discussed by the team, although often only one doctor (usually the consultant haematologist) will manage each case. Because myeloma is not common, and choosing the right treatment is sometimes complex, a second opinion may be required to ensure that the diagnosis is correct, that the treatment plan is appropriate and that all other options have been considered. Doctors are generally happy for a second opinion to be sought and a request for such will not cause offence to him/her or the medical team. The doctor or GP may be able to recommend another myeloma specialist and provide a written referral letter outlining the patient's current situation and plan for management. Choosing a non-conventional (alternative) approach to therapy
Some patients feel that they do not want to have any type of treatment because of fear of side effects and prefer to try an alternative approach such as dietary control. Unfortunately, there is no evidence that these alternative approaches work. It is important to remember that conventional treatments have been well tested in clinical studies and doctors have a clear understanding of how they work. The same cannot be said for alternative approaches. If an alternative method is preferred to control the disease, it is important to discuss the potential risks with a doctor. The medical team will need to be aware of any alternative methods used, particularly should conventional treatment be chosen at a later date.
Choosing not to accept active treatment
If a person decides not to accept any active treatment for myeloma there are many supportive measures available to help alleviate the symptoms of the disease. If specialist advice is needed with regard to symptoms such as pain, it may
be helpful to utilise a palliative care specialist, who will be able to provide
expertise in symptom control.
Indications for starting treatment
Before embarking on treatment, patients and doctors need to make important decisions about what treatment is best or most appropriate and when to receive it. The decision to start or not to start treatment is an important one. Not everyone diagnosed with myeloma will need treatment to control his or her myeloma immediately. Because currently available treatment is not curative and has side effects it is usual to wait until the myeloma is actively causing problems before starting treatment. Results from the tests and investigations listed earlier, along with other individual factors, will help determine when treatment should begin, what that treatment should be and provide a baseline against which response to treatment and disease progression can be measured.
What treatments are available?
There is no one standard treatment for myeloma, therapy is tailored to each patient. With that in mind, a patient can think of the treatment and manage-ment of myeloma as being in four categories. These are: • Active monitoring • Treatments to control the myeloma itself • Treatments for the symptoms and complications caused by the myeloma (supportive measures) • Treatment when the disease comes back (relapse) There is some overlap between these categories, since any treatment that controls myeloma will have the added benefit of reducing the complications and symptoms experienced. Treatments to manage myeloma are broadly summarised in the following table before being discussed in more detail separately.
The use of chemotherapy drugs, alone or in
standard dose
combination, to kill cancer cells. Most commonly used are Melphalan and Cyclophosphamide. These drugs are often used in combination with other anti myeloma treatments Thalidomide
Immune modulator drug (IMiD) given in tablet form. Shown to be effective against myeloma alone, or more commonly in combination with corticosteroids with or without chemotherapy Bortezomib
Proteasome inhibitor drug. Given via a quick injection (Velcade®)
into a vein (IV) or under the skin (subcutaneous). Shown to be effective against myeloma, alone or more commonly in combination with corticosteroid +/- chemotherapy Immune modulator drug (IMiD) given in tablet form. In the same class as thalidomide. Shown to be effective against myeloma alone, or more commonly in combination with a corticosteroid +/- chemotherapy Dexamethasone or prednisolone. Active against
myeloma. Can be used alone but more commonly in combination with chemotherapy and another antimyeloma agent (thalidomide, bortezomib, lenalidomide) High dose
The use of high doses of melphalan chemotherapy followed by blood stem cells to replace healthy cells
and stem cell
damaged by the chemotherapy transplant
Radiation
The use of high energy X-rays to damage myeloma cells Supportive
Therapies to alleviate symptoms and manage complications of the disease and its treatments. For
example:
Bisphosphonates – to manage bone disease
Antibiotics – to treat or prevent infections
Growth factors – to boost blood cell counts
Immunoglobulin Infusion – to boost levels of healthy
immunoglobulins and help prevent infections
Blood and platelet transfusions – to support lowered
blood counts
Anticoagulants – reduce risk of blood clots associated
with certain anti myeloma medications
Pain killers – to manage pain
The following sections describe the various treatments that are available in more depth and some of the circumstances under which particular treatments are used.
The Medical & Scientific Advisory Group (MSAG) of Myeloma Australia
published Clinical Practice Guidelines for the management of Multiple
Myeloma. This document was written to help guide specialists and other
health professionals in the management of myeloma. They are written
specifically for medical professionals and are available on the MFA website:
www.myeloma.org.au.
What treatment will be offered first?
Once it is decided that treatment is required to control the disease, both doctor and patient will determine the most suitable regime. It is important to remember that, although these treatments can be very effective to control the myeloma, even over long periods of time, they do not cure the disease.
The main treatment decision at diagnosis is to decide upon pathway 1 or 2, which are broadly termed as intensive or less intensive pathways.
1. Intensive Pathway
Initial treatment plus high dose chemotherapy and autologous stem cell transplantation (AuSCT). This is the standard upfront pathway for younger, fit patients (generally under 65 years of age, although biological fitness is a more important determinant than age).
2. Less intensive Pathway
Initial treatment without high dose chemotherapy and stem cell transplantation This is the standard upfront pathway for those older or less fit patients (generally over 65 years of age).
Does the person's myeloma require treatment yet?
Is person suitable for AuSCT?
Active monitoring
until symptoms present
or evidence of
3-6 Cycles
6-12 Cycles
oms and side eff
Has there been a response
to initial therapy
• Active
• Maintenance
Figure 3. For common combinations of therapy please see Table 4 p39 - 40 Most often, the initial treatment patients receive includes a triplet combination of a chemotherapy drug, a steroid and one of the newer drugs such as thalidomide, bortezomib or lenalidomide (common combinations listed in Table 4 p39-40). Combinations of drugs are used as each type of drug works differently to kill myeloma cells with the combined effect providing a higher chance of eradicating as much disease as possible.
Treatments are prescribed using protocols. These outline the combination of drugs used, dose per patient according to their height/weight or body surface area and the timing of doses. A course of treatment usually lasts for several months. It is given in cycles, i.e. a dose or a few days of treatment, followed by several days or weeks without treatment before the next dose is given. The exact details of the treatment schedule vary depending on the individual patient and the type of chemotherapy and medications required, the specialist is the best person to answer specific questions about treatment schedules. Common treatment protocols are available from the Cancer Treatments Online page of the Cancer Institute of NSW website. www.eviQ.org.au The total length of the treatment course often depends on which medication(s) are prescribed and the response to treatment, but is likely to last between 3 and 12 months.
In the sections below, the different medications used initially to treat myeloma are described and some common combinations listed. Some possible reasons why an individual would have one treatment combination over another are also described. Conventional Chemotherapy Based Combinations
What is chemotherapy?
Chemotherapy drugs include a range of potent drugs that are intended to kill the myeloma cells in the bone marrow. Chemotherapy works by damaging myeloma cells and preventing them from being able to divide and reproduce.
Chemotherapy drugs attack cells in the body that divide rapidly, such as myeloma cells, but also may affect other rapidly dividing cells such as those in the bone marrow, hair follicles and the lining of the mouth and the stomach. Unfortunately this means that chemotherapy treatment can have side effects.
How is chemotherapy given?
Some chemotherapy drugs can be taken by mouth (oral) and others are given as an infusion into a vein (intravenous infusion or IV) or under the skin (subcutaneous or SC). Oral chemotherapy treatments can be taken at home, but hospital visits are required to receive the intravenous chemotherapy. The type of chemotherapy prescribed for myeloma patients depends on the individual and what is most suitable for them and their disease at any particular point in time. Common types used to manage myeloma include melphalan, cyclophosphamide and doxorubicin, although others are also used in certain cases (see Table 4 p39).
Although chemotherapy can be given on its own as a treatment, it is more commonly given in combination with steroids, most commonly dexamethasone or prednisolone. The newer drugs thalidomide, bortezomib or lenalidomide, may also be given in combination with steroids, with or without chemotherapy. See Table 4 p39 for some common combinations.
What are the possible side effects of chemotherapy?
Each different type of chemotherapy drug has its own side effects, and even the same kind of chemotherapy produces different reactions in different people. It may be helpful to remember that almost all side effects are only short term, are usually easily managed and should gradually disappear once the treatment has stopped. Some of the most common side effects of many chemotherapy drugs are nausea and / or vomiting, hair loss (alopecia), sore mouth (or mouth ulcers) and diarrhoea. Certain kinds of chemotherapy can cause infertility. If preserving fertility is a priority for any individual, a discussion must take place with the doctor before treatment starts.
Patient information leaflets outlining the side effects of each drug are readily available from the doctor, nurse or pharmacist providing treatment.
Report side effects to the medical team straight away so they can be addressed effectively. Supportive medications to minimise side effects can be given and in some circumstances, doses and scheduling of treatment can also be altered to manage side effects. A comprehensive guide on chemotherapy is produced by the Cancer Council and can be found on their website or by calling The Cancer Institute NSW – ‘eviQ – Cancer Treatments Online' produces a range of information fact sheets on different chemotherapy drugs, common protocols and common side effects of chemotherapy that can be accessed on their website, What are steroids and how do they work?
Steroids are hormonal substances naturally produced in the body. There are many different types of synthetically made steroids used to manage a range of disorders. Those used in the treatment of myeloma are known as glucocorticoids. These steroids can modify the body's immune responses, suppress inflammation and cause myeloma cells to die. How are steroids given?
The two most commonly used steroids in myeloma are dexamethasone and prednisolone. Steroids can be given on their own as a treatment for myeloma but are more commonly used in combination with chemotherapy or other anti myeloma drugs. Although they can be given as an infusion into a vein, they are more commonly given as a course of tablets. Tablets should be taken with food or milk to help protect the stomach from irritation. As the doses used in myeloma are often high, several tablets may be needed to be taken at one time. Steroid treatment in myeloma is typically given in high doses but for short periods only. What are the possible side effects of steroids?
Side effects do vary according to the dose and duration of treatment. It is important to remember that each person's reaction to steroids may be different and that side effects, if any, are temporary and should resolve when the steroids are stopped. Learning from experience: Side effects related to steroids often follow a very predictable pattern. Learning the pattern of side effects over a treatment cycle or period of time can be helped by keeping a side effect journal. Once the pattern of side effects has been found it is possible to work towards finding ways to manage these. More common side effects of steroids are listed below. Side effect
Gastritis
• Take with or after food or milk • Medication to prevent stomach Stomach irritation or pain
irritation may be prescribed • Inform the doctor if heartburn or stomach pain is experienced Mood and energy changes
• Commonly heightened mood and often related to the days
energy on steroid days and lower steroids are taken
mood and energy on days immediately following steroid dose • Inform family and friends of such side Mood swings
effects to help them understand the altered behaviour • Some people find taking exercise, even a good walk, can help minimise agitation and irritability • Talk with the doctor if mood changes are acute or unmanageable • Take in the morning to avoid • Some people find sleeping tablets are helpful on the days they take steroids Increased or unstable blood
• Monitor blood glucose level closely, especially if diabetic Let down effect
• Feeling of low mood and energy in the days following steroid dose • May require tapering of steroid doses if • Some people have found that drinking isotonic (sports) drinks can help reduce the ‘hangover effect' on the days following steroid dose • Manage lifestyle and activities around Neutropenia; Increased risk
• Be aware of common signs of of infection due to lowered
infections such as temperature above white cells and neutrophils
38oC, having a productive cough, having shivers or chills, swelling or inflammation at site of cut or injury • Report any signs of infection to a GP or • Adopt healthy snacking to avoid weight • See a dietician for further advice Flushing of face
• Commonly on day of taking steroid See our Steroid Therapy fact sheet for more information. www.myeloma.org.au – 1800 MYELOMA (693 566)
Immunomodulatory Drugs (IMiDs)
How do IMiDs work in myeloma?
Drugs in this family include thalidomide (Thalomid®), lenalidomide (Revlimid®)
and pomalidomide (Pomalyst®) (which is currently being assessed in clinical
trials)
IMiDs work in a different way to conventional chemotherapy drugs. Their exact mechanism of action is the subject of ongoing research. It is likely that they: 1. Suppress the growth and survival of myeloma cells and also directly kills 2. Inhibit the growth of new blood vessels (angiogenesis), which myeloma
cells need to grow and survive 3. Stimulate the body's immune system to attack myeloma cells4. Block the activity of chemicals involved in the growth and survival of It seems likely that some or all of these ways of working are relevant to how the drugs in the IMiD group can be effective against myeloma.
Thalidomide is a drug used in a variety of combinations and at various times during the course of the disease. It can either be used as part of the first line of therapy (upfront therapy) or after the myeloma has become active again after a period of control (relapse). How is thalidomide taken?
Thalidomide is given as a daily capsule which is normally taken in the evening as it can cause drowsiness. It can be used on its own, or more commonly in combination with a steroid (dexamethasone or prednisolone) and a chemotherapy drug (melphalan or cyclophosphamide). Some of the combinations commonly used are listed in Table 4 p39.
What are the potential side effects of thalidomide?
Side effects vary according to the dose and duration of treatment. It is important to remember that each person's reaction to thalidomide may be different and that side effects, if any, are temporary and should resolve or diminish when the thalidomide is stopped. Thalidomide can cause a range of side effects; the more common ones are listed below. • Peripheral neuropathy • Thrombosis (blood clots) • Low blood pressure; feeling dizzy or faint, especially when standing too See Table 3 for a more details of each side effect. It is important to inform the doctor or nurse if any side effects are experienced.
Lenalidomide is chemically similar to thalidomide but works through a different mechanism. It often works even if patients have had thalidomide previously. Lenalidomide is available in Australia to treat myeloma after initial treatment, including thalidomide, high dose therapy and stem cell transplant (if suitable) in those whose disease has come back.
How is lenalidomide taken?
Lenalidomide is given as a tablet 21 days out of every 28, in the pattern 3 weeks of treatment and 1 week rest. The starting dose is usually 25mg per day but may be reduced in the presence of complications such as kidney impairment or low blood counts. The treatment is ongoing until either the myeloma stops responding or any side effects make lenalidomide an unsuitable option. Lenalidomide can be given as treatment on its own but more commonly is given in combination with a steroid such as dexamethasone. See Table 4 p40.
What are the potential side effects of lenalidomide?
Lenalidomide is generally well tolerated and has fewer side effects than thalidomide. The most common side effects are listed below. • Thrombosis (blood clots) • Lowered white cell count (neutropenia) • Lowered platelet count (thrombocytopenia)See Table 3 for a more details of each side effect. It is important to inform the doctor if any side effects are experienced.
Bortezomib is an anticancer drug that works in a different way to chemotherapy and the IMiD drugs. Bortezomib is a ‘proteasome inhibitor'. Proteasomes are present in all cells and help regulate cell function and growth. Bortezomib interferes with the way that proteasomes work, causing cancer cells to stop growing and die. Cancer cells appear to be more sensitive to the effects of bortezomib than healthy cells.
Bortezomib is either given as a quick injection into a vein intravenously (IV) lasting only 3-5 seconds or as an injection under the skin subcutaneously (SC). Bortezomib can be given on a weekly schedule or twice weekly schedule and for differing lengths of time. The specialist will advise how often bortezomib is required and for how long in each individual case. Bortezomib is often given in combination with dexamethasone and cyclophosphamide, known by the acronym CyBorD or VCD. For a list of these combinations, see Table 4 p40. Although patients do not normally need to be admitted to hospital to have treatment with bortezomib, they do have to travel to the hospital regularly to receive bortezomib in the day chemotherapy unit. What are the potential side effects of bortezomib? In general the side effects of bortezomib are mild to moderate however this can vary between patients. It is important to highlight side effects promptly to the doctor or nurse. The most common side effects are listed below.
• Lowered white cell count (Neutropenia) • Lowered platelet count (Thrombocytopenia) • Gastrointestinal problems; nausea, vomiting, diarrhoea and constipation • Peripheral neuropathy • Low blood pressure; feeling dizzy or faint, especially when standing • Increased risk of a shingles infectionDrinking plenty of water on the days of treatment can reduce the risk of some of these effects. Blood tests will be taken at regular intervals during therapy to watch for the effects of toxicity or lowered platelet counts. If signs of peripheral neuropathy develop inform a doctor or nurse. See Table 3 for a more details of each side effect. It is important to inform the doctor if any side effects are experienced.
Side effect
• Thalidomide is a known sedative and therefore should be taken in the evening • Take a few hours before bedtime if it is hard to rise in the morning • Maintain a high fibre diet with plenty of fluid. Aim to drink 2.5 - 3 litres of fluid a day • Regular exercise as tolerated • Use of laxatives is commonly required • If occurs, is likely to happen within the first • Inform the doctor if a rash appears • Likely to improve on its own • May require stopping the drug if severe Peripheral neuropathy
• More common with high doses and after (tingling, burning, pain,
taking thalidomide or bortezomib over and loss of feeling in
longer periods of time. Less common with hands and feet)
• Inform the specialist if symptoms of neuropathy appear • May require a dose reduction • **See MFA peripheral neuropathy booklet for a comprehensive list of suggestions to help reduce the impact of peripheral neuropathy Thrombosis – Risk of
• More common if other risk factors are developing blood clots
present such as obesity, older age, high myeloma protein and previous history of DVT – deep vein
heart disease or stroke thromboses (commonly
• Often requires the taking of a blood in the lower leg)
thinning medication such as aspirin, PE – pulmonary emboli
warfarin or low molecular weight heparin (clot in the vessels of
to reduce the risk of blood clots the lungs)
• Symptoms of a DVT include swelling, redness, warmth and tenderness in the leg • Symptoms of a PE include shortness of breath and chest pain • Inform the doctor at once if symptoms of a blood clot occur.
Thrombocytopenia: low
• If platelets become very low, there is an levels of platelets
increased risk of bleeding. The doctor may recommend a platelet transfusion • Bruising can be a sign of lowered platelet Neutropenia: low levels
• Regular blood tests are used to check cell of neutrophils, a type of
counts during treatment white blood cell
• If the number of these cells is very low, the doctor may change the dose and/or schedule of the treatment • Be aware of the signs and symptoms of infection such as a temperature above 38ºC, having a productive cough, experiencing shivers or chills, swelling or redness at site of a cut or injury • Report any signs of infection to the GP or • Keep well hydrated Problems: nausea,
(2.5 - 3 litres fluid a day). vomiting, diarrhoea,
• Take anti sickness medication as • The BRAT diet may help (bananas, rice, apple sauce, toast) • Take antidiarrhoeal medication as prescribed (e.g. loperamide) For constipation: • High fibre foods • Keep well hydrated • Take laxatives as required Low blood pressure;
• If also taking drugs that lower blood feeling dizzy or faint,
pressure, medications might need to be especially when
standing up too quickly
• Drink plenty of fluids especially on the days when having treatment. If insufficient liquids are taken the doctor may need to administer some intravenous fluids prior to therapy if attending a clinic.
Ask the specialist for up to date information regarding these drugs, and their suitability and availability.
Combinations of treatments
Although sometimes a drug is used on its own to treat myeloma, more commonly combinations of drugs are used. The following section explores some of the different common combinations used and the rationale for their use. Initial therapy combinations for patients eligible for high dose
therapy and stem cell rescue (induction therapy)
The group of patients suitable for this approach to initial treatment would include those who are younger and fitter. Most commonly this would be those under 65yrs of age but increasingly it is the general health of the patient that is considered and not just the individual's age. This treatment approach is generally considered more aggressive and toxic and can cause unacceptable side effects in older, less fit patients. The risk of any treatment choice needs to be balanced against the likely benefits. The aim of initial therapy is to gain control over the myeloma and reduce its effects on the body. Typically, this will involve 3 to 6 cycles of therapy with a cycle being 3 to 4 weeks in length (total treatment of 3-6months). The most common treatment regimens (protocols) used when a transplant
is planned are listed in Table 4 p39-40. These combinations may include
drugs of which some are given into a vein (intravenous, IV), under the skin
(subcutaneous, sc) and some are given orally. An acronym consisting of single
letters is used for convenience. Each of the letters in these combinations
represents a different drug, e.g. in the case of CVD they are Cyclophosphamide,
Velcade and Dexamethasone.
Initial therapy combinations for patients not eligible for high dose
therapy and stem cell rescue (induction therapy)
If a transplant is not planned then similar combinations of therapy are recommended. These include bortezomib or thalidomide based treatment. When deciding on the best treatment in this group of patients, considerations of an older, and potentially less fit patient are taken into account. Frailty and presence of pre-existing health issues can be more common and the ability to tolerate combination therapies and frequency of hospital visits need to be taken into account when deciding on best treatment for any individual. Newer combinations, using lenalidomide (Revlimid®) are being studied in both those eligible for transplant and those not, mostly in the context of clinical studies. It is expected that in time these drugs will be used as part of initial treatment for myeloma. Disclaimer
Due to the pace of change in the treatment of myeloma it is beyond the scope of this guide to list optimum combinations of treatment for each phase of the disease and in any particular individual. We have chosen therefore, to present a table of the most common combinations. For more specific information about which treatment combination is most suitable for individual cases, patients need to refer to their specialist.
Newer drug combinations are often available first as part of organised clinical trials. Ask the specialist for more information about this option.
Table 4 – Commonly Used Therapy Combinations in Myeloma Chemotherapy based combinations
Thalidomide (Thalomid®) based combinations
Bortezomib (Velcade®) based combinations
CyBorD (also
VcAD (also
Adriamycin (Doxorubicin) Lenalidomide (Revlimid®) based combinations
New drugs are being approved for re-imbursement through the PBS each year in Australia. Drugs are approved for a specific indication which determines who with myeloma can access them and in combination with what other drugs. The haematologist will recommend the most effective regime available in each circumstance. Ask the nurse and specialist for further information on a particular treatment regimen, including advantages, disadvantages and potential side effects.
High Dose Therapy and Autologous Stem Cell
Transplantation (AuSCT)
What is high dose therapy and stem cell transplantation
and why is it needed?
Standard chemotherapy, given alone or in combination, is an effective way of treating myeloma. In the majority of cases chemotherapy is easy to administer and can often be taken at home. However, a major drawback of chemotherapy is the inability to give high doses safely. This is because chemotherapy, particularly in higher doses, kills healthy, good cells as well as myeloma cells. This can result in blood production being severely affected and blood cells may
fall to dangerously low levels, causing a number of potentially serious problems
such as neutropenia and thrombocytopenia.
An autologous stem cell transplant uses healthy cells, previously collected from the patient's blood, to offer a way round the problem. It provides a means of giving higher doses of chemotherapy, to consolidate previous chemotherapy treatment, without causing permanent damage to blood cell production. Giving back previously collected healthy stem cells after high dose chemo-therapy effectively ‘rescues' the patient's bone marrow. It means that healthy blood cell production can continue until the bone marrow, damaged by the high doses of chemotherapy, recovers and produces new cells. High dose therapy and stem cell transplantation therefore has the ability to destroy in a safe way more myeloma cells than would be possible with lower doses of chemotherapy, improve the duration of remission and provide better quality of life. It is worth noting however, that myeloma is a very individual disease. Each patient's disease has its own distinct characteristics, which may affect the outcome of high dose therapy and stem cell transplantation and not all patients achieve the desired response. For a small group of younger patients, an allogeneic transplant may be used after an autologous stem cell transplantation. Allogeneic transplantation is discussed later in this guide (see p47). What are blood stem cells?
Blood forming stem cells exist in the bone marrow. They have the capacity to divide and develop into the three main types of cells found in the blood and are a vital component of high dose therapy and stem cell transplantation (see Figure 4).
Figure 4. Blood stem cell diagram High dose therapy and stem cell transplantation – the process
The whole process, from the initial discussion with the doctor to recovery after the transplant, can take several months and can be daunting if approached as a whole. It is often easier to prepare for and face each stage separately. Due to the nature of this treatment option, only hospitals with appropriate accreditation and medical and nursing experience perform high dose therapy and stem cell transplantation. This may mean a referral to another hospital for this portion of treatment and care. Induction chemotherapy / treatment
The combinations of treatments discussed in the previous chapter are required before high dose therapy and stem cell transplantation can take place. This initial treatment, known as induction therapy, aims to reduce the amount of myeloma in the body and help relieve the symptoms. There are a number of induction regimens to choose from, all of which have been shown to be comparably effective. Individual disease factors as well as doctor / patient preference will determine which regimen is the most appropriate to use.
Courses of induction therapy usually last for several months and are given in cycles. The number of cycles given will depend on individual patient factors and how the myeloma responds, however 3 to 6 months would be a common duration of therapy.
How are stem cells collected – ‘Mobilisation'
Stem cells that are collected from peripheral blood are referred to as peripheral blood stem cells or ‘PBSC'. These stem cells live and grow in the bone marrow. It is necessary then to move the stem cells into the blood stream in order to be able to collect them. This is achieved by giving a dose of chemotherapy, followed by a special type
of drug called a ‘growth factor'. The chemotherapy kills off a population of
mature blood cells causing new cells to grow in their place. Growth factors
are then given daily to increase the number of stem cells in the bone marrow,
causing them to spill over into the blood where they can be collected more
easily. The growth factors are given consecutively over about 7 to 10 days
before there are enough stem cells to be collected. The administration of the
chemotherapy may require a few days in hospital but the remainder of the
mobilisation process can be carried out as an outpatient.
Once the stem cell count is high enough, collection will take place using a
special machine known as a cell separator or apheresis machine. This process
is carried out in the day care area of the hospital. Collecting the stem cells
usually takes about 3 to 4 hours lying down on a bed or special lounge chair
with a line connected into a vein in each arm.
Blood is taken from one arm and goes through the line, into the apheresis machine. The blood is centrifuged to separate the various cell components. Stem cells are drawn off and the remaining blood returned through the intravenous line into the other arm. During the stem cell collection process, the most common side effect is a cramp like or tingling sensation in the hands, feet or around the mouth. This happens because an anti coagulant agent is used to stop the blood from clotting in the machine and this can cause a drop in the body's calcium levels. This is usually easily corrected by drinking some milk. It is normal to feel tired after the collection and need to rest that evening.
Often, enough cells will be collected in just one session but sometimes another session the following day is required to collect enough stem cells to transplant. Receiving the high dose chemotherapy
After the stem cells have been frozen and stored, the next step is to come into hospital to receive the high dose chemotherapy followed by the transplant of stem cells. There is usually a gap of about a month between the collection of stem cells and the receiving of high dose chemotherapy. Although it can vary between patients, this part of the process usually requires a 3 to 4 week stay in hospital. Some transplant centres carry out this process as a mixture of inpatient and outpatient care. Ask the specialist or nurse to explain these details.
The high dose chemotherapy is often referred to as ‘conditioning' therapy and is given through a vein, usually via a central line (e.g. Hickman®catheter). The insertion of the central line involves a small procedure to have a narrow plastic central line inserted into a large vein in the upper chest. This form of central line allows all of the chemotherapy to be given without inserting a new line into a vein at each visit. Blood samples can also be taken through this line. A diagram of a Hickman catheter can be seen on the following page.
Figure 5. Hickman Catheter diagram The high dose chemotherapy is called melphalan, an effective drug in treating myeloma. Before and after melphalan is given, large amounts of fluid are given through a drip, to prevent dehydration and kidney damage caused by the toxicity of the chemotherapy. The most common side effect of melphalan is nausea and gastric upset, commonly diarrhoea. These symptoms can be ongoing for 7 to 10 days but a range of medications will be given to minimise these side effects. Any side effects should resolve as the blood counts improve.
Within a day or so of completing the high dose melphalan, the frozen stem cells are thawed and given back as an intravenous drip. This process is relatively straightforward and takes roughly 15 minutes per bag of stem cells. Once the stem cells are put back into the blood stream, they settle in the bone marrow and develop into new blood forming cells – a process known as engraftment. This takes on average 10-14 days. Once blood cell numbers have returned to within safe levels and there are no signs of infection or other health issues requiring treatment, it is safe to go home. During the crucial time waiting for engraftment there will be an increased risk of infections and the team will advise ways to minimise this. This will include a range of supportive medications like antibiotics and other anti microbials. It is important to maintain good hygiene with daily showers and changes of clothes. The mouth is a common route for infection so maintaining good oral hygiene is also important. One of the side effects of the chemotherapy can be a sore, dry mouth and a variety of cleaning or soothing agents may be recommended by the nursing team. There is some evidence to show that sucking ice for 30 minutes before the melphalan infusion, during and for 2 hours after the melphalan has finished, can reduce the severity of a sore mouth (mucositis). This is called ‘cryotherapy' and seems to work by cooling the mouth and preventing damage to the lining of the mouth caused by the melphalan. Ask the nurse or doctor if this technique is appropriate.
Even though the appetite may be suppressed it is important to maintain a ‘clean diet' to avoid the chance of picking up a gastric infection. This involves fresh cooked food, no raw meat or fish or unpasteurised dairy foods. Ask the dietician for more information on a clean diet. Fatigue is common during the process of engraftment, as is lack of concentration. This will improve over time but can often take months to recover to the pre transplant state.
Supportive care and follow up when at home
The recovery time at home after a transplant can be a challenging one. Energy levels often take months to return to normal and there will be regular specialist visits to check the blood cell numbers are returning to normal.
There will still be a risk of infections therefore it is important to maintain good hygiene, avoid people with infections and inform the doctor of signs and symptoms of infection, promptly. There will be a range of medications to protect the body from infections and 6 to 12 months post transplant some repeat vaccinations will be required to regain childhood immunity that may have been lost. See the risk of infection section on page 55 for more information.
What are the types of transplant that are available?
If stem cells from oneself are used for the transplant, it is called an autologous transplant; if stem cells from a donor are used, it is called an allogeneic transplant. It is very important to understand that there are significant differences between these two types of transplant, both in their potential benefits and the risks involved.
Autologous transplantation (AuSCT)
Autologous transplants use stem cells collected from the patient (auto = self). This is the most common form of transplantation used in myeloma. In this kind of transplant, bone marrow recovery takes about two weeks. Blood and platelet transfusions may be required until the bone marrow recovers and antibiotics are usually given to prevent infections. The main advantage is the possibility of achieving an excellent response and long remission with a low level of risk from the treatment. Disadvantages include more toxicity than standard dose chemotherapy and the reality that relapses still occur.
Allogeneic stem cell transplantation (AlloSCT)
Allogeneic transplantation (allo – from the Greek word meaning ‘other') involves collecting stem cells from either the bone marrow or peripheral blood of another person (the donor) and giving them to the patient (recipient).
Because myeloma effectively ‘shuts off' a vital part of the immune system that would normally kill myeloma cells, allogeneic transplants aim to use the immune system from the donated cells to help directly fight the myeloma in the patient (recipient).
The goal is for the donated cells to eventually replace the immune system of the patient and therefore continue to fight off the myeloma.
A transplant of stem cells from a donor has two main advantages: the transplanted cells do not contain any myeloma cells (no contamination), and the donor's immune system has the ability to recognise and destroy myeloma cells. The disadvantage of using a donor is that the donor's immune cells will recognise the patient as ‘foreign', and this can trigger a serious complication called graft versus host disease (GvHD). This is an adverse reaction that
can affect the skin, liver and gut, causing serious problems, which may even
be fatal.
In those patients who cope with the transplant and the complications, a number may have no detectable myeloma and potentially achieve a longer remission. Even if the myeloma does recur, the transfusion of more of the donor's immune cells, collected from their blood, can help to destroy the myeloma cells again. This procedure is called a donor lymphocyte infusion, or DLI. If a patient does not have a brother or sister with the same tissue type as the patient, it is sometimes possible to find a donor who is not related. This type of transplant is called a matched / volunteer unrelated donor (or M / VUD) transplant.
The problems associated with this form of transplant are even greater than with a related donor. These transplants are very rare, they do happen but not enough to show what the long term benefit may be.
In order to reduce the risks associated with an allogeneic transplant, while
still maintaining the benefits of giving donor cells, a newer type of transplant
has been developed. This is the reduced intensity conditioning transplant
(RIC) or the mini allogeneic transplant, which involves giving a lower dose
of chemotherapy than would be used for a standard allogeneic transplant. For
patients suitable for an allogeneic transplant, it is now common for their doctors
to recommend a standard AuSCT followed by a reduced intensity allograft.
For a more comprehensive guide on the process of high dose therapy and stem cell transplantation contact the Leukaemia Foundation on 1800 620 420 or visit www.leukaemia.org.au
For information about finding an allogeneic donor, visit the Australian Bone Marrow Donor Registry at www.abmdr.org.au
After transplant or treatment has brought the myeloma under control, maintenance treatment may be needed to prolong the period of response to treatment, whether in remission or plateau. Steroids, such as dexamethasone or prednisolone, can be used as maintenance treatments. Thalidomide has also been found to prolong the response to treatment in those patients who don't get a good response with stem cell transplants. However, not all patients will benefit from these treatments and any benefits will have to be balanced against the side effects that may occur.
Other treatments such as bortezomib (Velcade®) and lenalidomide (Revlimid®) are being studied in clinical trials as potential maintenance treatments.
What are the treatments for symptoms
and complications due to myeloma?
Myeloma can affect the body in several ways. This is due both to the activity of the myeloma cells and to the release of a variety of proteins and other chemicals into the local bone marrow microenvironment and directly into the blood stream.
It is important to remember that not everyone will experience all of these and that treatments are available.
The most common symptoms and complications of myeloma, how they affect the patient, and how they are managed, are described below.
Bone disease
Bone disease is one of the most common complications of myeloma. The
myeloma cells release chemicals that activate osteoclast cells, which destroy
bone, and block osteoblast cells, which normally repair damaged bone.
When this happens, the bone is broken down faster than it can be repaired, leading to bone pain, bone lesions or even fractures. The middle or lower back, the rib cage and the hips are the most frequently affected areas. Fractures occur most often in the spine (vertebrae) or ribs. Fractures can sometimes occur with only minor pressure or injury. Fractures of the vertebrae can lead to their collapse causing pain due to trapped nerves, loss of height and curvature of the spine. The rapid breakdown of bone can lead to an increase in the blood calcium level (hypercalcaemia) which can cause symptoms of confusion, constipation and thirst.
A group of drugs called bisphosphonates are used to help manage myeloma bone disease.
Bisphosphonates help in myeloma in several ways. They help to correct hypercalcaemia, control existing bone disease, and slow down any further bone destruction. They work by binding to calcium in the bone and by blocking the activity of the osteoclast cells that break down the bone. Evidence from clinical studies with bisphosphonates has shown that there is a benefit to be gained by giving bisphosphonates to any patient with active myeloma, whether they have symptoms of bone disease or not. In Australia, three bisphosphonates are currently licensed for the treatment of hypercalcaemia and / or bone disease in myeloma. They are: • Zoledronic acid (Zometa®), which is given as a monthly intravenous infusion • Pamidronate (Aredia®), which is given as a monthly intravenous infusion • Sodium Clodronate (Bonefos®), which is taken by mouth as tablets Osteonecrosis of the Jaw – ONJ
A complication associated with bisphosphonate therapy is a condition called osteonecrosis of the jaw (ONJ). It is seen in a small number of patients receiving bisphosphonate therapy. ONJ presents as a persistent non healing wound in the mouth most commonly following tooth extraction or dental surgery. It can cause pain, may become infected and is slow to heal. It is important to note that bisphosphonate therapy is an important part of the supportive care of those with myeloma. Bisphosphonates reduce the risk of further bone disease, bone pain and high calcium levels in the blood. The low risk of developing this rare complication needs to be balanced with the obvious proven benefits of these drugs.
Who is at greater risk of getting ONJ?
The risk of developing ONJ in those with myeloma is thought to be less than 10% overall. Some factors are known that increase the risk of developing ONJ: • Prolonged use of bisphosphonates (> 12months) • Undergoing invasive dental procedures such as tooth extraction or surgery exposing jaw bone • Those with poor dental health • Those with diabetes • Having poorly fitting oral appliances (e.g. dentures) How to prevent ONJ?
Avoiding the risk factors above can minimise the risk of developing ONJ. It is also recommended that all patients have a thorough dental check before they start treatment with bisphosphonates and undertake any invasive dental work before they commence therapy. Six monthly dental assessments should occur during therapy. The dentist should be informed if patients are receiving bisphosphonate treatment.
If a tooth extraction or dental surgery is required whilst on bisphosphonate therapy, ask the dentist and specialist to have a discussion in advance to decide on the best treatment. It is often advised to have a break from bisphosphonate therapy whilst extraction or surgery is undertaken and until complete healing has occurred. A course of antibiotics may also be required and maintaining impeccable oral hygiene is essential.
How to manage ONJ should it occur?
Therapy to manage ONJ, should it occur, is conservative and will depend on individual risk factors, such as bone disease or whether the myeloma is stable or in remission. The following gives some guidance as to the management of ONJ but concerns can be discussed with the specialist and dentist.
• Regular mouth washes – chlorhexidine 0.2% • Regular dental review • A ‘drug holiday' from bisphosphonate therapyIt is now recommended that the use of bisphosphonates be assessed every 12 months. A decision to continue or modify bisphosphonate therapy should be made based on the patient's risk of a skeletal injury.
Guidelines are available on the recommendations for the prevention and treatment of ONJ in patients receiving bisphosphonate therapy for myeloma. To obtain a copy for your dentist, please contact the myeloma support nurses on 1800 MYELOMA (693 566) or visit the
Pain is the most common symptom for patients diagnosed with myeloma and is often related to underlying bone disease. Effective management of pain and its relationship to quality of life is critical and just as important as the treatment for the actual myeloma. Pain is very specific to the individual and treatment will vary. Medication should aim to provide continuous pain relief whenever possible with a minimum of drug related side effects. Complementary therapies such as relaxation techniques, aromatherapy and hypnosis have also shown to have some benefit for individual patients. In some more serious cases medication and / or complementary therapies will need to be supplemented by other types of treatment such as: • Localised radiotherapy: This has been shown to help control ‘hot spots' of active bone disease and pain.
• Vertebroplasty: Vertebral collapse in the spine can often occur with
myeloma. Vertebroplasty is a procedure which involves the injection of cement into the affected vertebrae body by a specialist radiologist. This procedure can significantly reduce pain.
For a comprehensive booklet on ‘Overcoming Cancer Pain', ‘Understanding Complementary Therapies' or a ‘Relaxation for People with Cancer' CD, contact the Cancer Council on 13 11 20
or visit their website www.cancercouncil.com.au
Fatigue is well recognised in those with myeloma. It is described as a physical, emotional and / or cognitive tiredness or exhaustion related to myeloma or its treatment, which interferes with usual functioning. The most important part of treating fatigue is actually recognising it. This means describing these feelings to the doctor. Fatigue is often described as a vicious cycle, but the cycle can be broken, allowing it to be managed. Planning activities to avoid becoming overtired is something both patient and carers can do together. Other strategies to help reduce fatigue include eating a healthy, balanced diet, taking regular light exercise and ensuring adequate sleep.
Fatigue caused by anaemia can be treated with blood transfusions and in certain cases also with a drug called erythropoietin. See also the section on anaemia below.
Kidney problems can occur in myeloma for a variety of reasons. The abnormal protein produced by myeloma cells can damage the kidneys; this is particularly common with the Bence Jones protein. Other complications of myeloma, such as dehydration and hypercalcaemia, as well as some of the drugs used to treat myeloma and its complications can also cause kidney damage.
The most important method to reduce the risk of kidney damage is to drink plenty of fluid. Drinking 3 litres of fluid per day is optimal. This includes all fluids from tea and coffee, fruit juice, milk and water. Some people find it useful to keep a bottle of water with them at all times so they always have a drink to hand. Avoid using a certain type of painkillers called a non steroidal anti inflammatory drug ‘NSAIDs' such as naprosyn or ibuprofen (Nurofen®). These drugs may contribute to kidney problems. The ‘contrast dye' given during certain types of scans (including CT scans) can also harm the kidney and should be avoided if possible. Treatment of kidney damage in myeloma depends on the cause. In many
cases, the kidney damage is temporary and your kidneys can recover. In a small
proportion of patients, the kidney problems become permanent requiring a
regular treatment called kidney dialysis. This is a way of filtering the blood using
a dialysis machine in the same way that kidneys would do if they were healthy.
Anaemia and infections
In adults, almost all red blood cells, white blood cells and platelets are made in the bone marrow. Red blood cells contain a protein called haemoglobin, which carries oxygen around the body. White blood cells help the body fight infection. Platelets are small cells that circulate in the blood, and are important for helping the blood to clot.
Myeloma cells crowd out normal cells in the bone marrow and create conditions that favour themselves, so fewer blood cells are produced. This shortage of blood cells can lead to conditions such as anaemia or to more frequent infections. Table 5 – Complications of reduced blood cells: Too few red blood cells result in a low haemaglobin level. This leads to tiredness and weakness Low levels of white blood cells, in particular the neutrophils, can make infections more likely Low levels of platelets may cause bruising or bleeding Anaemia is a reduction in the number of red blood cells or the oxygen carrying haemoglobin they contain. It can occur as a result of the myeloma or as a side effect of treatment and can cause symptoms of fatigue and weakness.
Anaemia does not always need treatment because the bone marrow is often able to recover, especially if treatment brings the myeloma under control.
If anaemia needs treatment, a blood transfusion can help, there is also a drug called erythropoietin (or EPO) which can stimulate the body to produce more red blood cells. In Australia, EPO is available to those who have kidney damage.
If the platelet count falls to very low levels, it can be boosted by a transfusion of platelets.
Risk of infection
Low white cell counts may not always need to be treated, but symptoms of infection should be taken seriously (such as fever, coughing up green phlegm, pain in passing urine, or diarrhoea) by notifying a doctor straight away. It is useful for patients to keep a thermometer at home to take their temperature if feeling unwell. If the temperature display is equal to or greater than 38˚C a doctor should be informed immediately. If the white cell count falls very low, the doctor may prescribe a course of antibiotics to try to prevent infections before they take hold. There are also drugs (called growth factors) that can stimulate the body to produce more white blood cells.
Having an annual flu vaccination is generally recommended for people with myeloma and those living in the same household. This would not be recommended if the immune system was very low or someone had an active infection. Check with the specialist or GP to see if the flu vaccination would be beneficial.
Key Points
• Be honest about any problems. Describing them as accurately as possible
will help get the right treatment.
• Acting early can reduce the number and severity of the complications associated with myeloma.
• Bone disease can be treated effectively with bisphosphonates, and early treatment can slow down bone problems.
• Drink plenty of water / fluids to prevent kidney problems – aim for 3 litres • If buying painkillers, tell the pharmacist to avoid nonsteroidal anti inflammatory drugs.
• Tell the doctor or nurse immediately if there is any concern about an infection.
For more comprehensive information sheets on the immune system, bone disease, pain and fatigue or the peripheral neuropathy booklet please contact the myeloma support nurses on 1800 MYELOMA
(693 566) or download further information sheets via our website
How is myeloma treated when it becomes
active again?
Treatment for relapsed or resistant myeloma
When myeloma returns, it is called a relapse or disease progression. This can be a very disappointing and distressing time for patients, their families and carers. Talking things over with the doctor, family / carer or another patient can help. Myeloma Australia or one of the organisations listed at the back of this guide are other good sources of support and information.
When myeloma returns, patient and doctor will consider which treatment will be needed to try to regain control of the disease. This may already have been discussed in the initial treatment plan. However, because the risks and benefits of treatment are not as clear in people whose myeloma has relapsed, many doctors like to discuss all the options again, as views and the disease characteristics may have changed. In some patients, the original treatment can be repeated successfully, especially if the initial response to treatment was good. In other patients, the myeloma may not respond to the treatment that was used previously; this is called resistant or refractory disease. If the myeloma is resistant / refractory to the original therapy, there are still many options available.
• Thalidomide (Thalomid®) based combination • Bortezomib (Velcade®) based combination • Lenalidomide (Revlimid®) based combination • Trying a different type of chemotherapy combination • Undergoing another high dose therapy and stem cell transplantation • One of several newer agents not yet freely available in Australia but available within clinical trials Trying a different type of chemotherapy
If the myeloma is no longer responding (refractory) to one type of chemotherapy
such as melphalan, a patient may respond to more intensive combinations
such as DT-PACE (Dexamethasone, Thalidomide, Cisplatin, Adriamycin,
Cyclophosphamide, Etoposide). These regimes may be an option in younger
patients to regain disease control so that high dose therapy and stem cell
transplantation may still take place.
If not used as front line treatment already, thalidomide alone, in combination with dexamethasone or with dexamethasone plus cyclophosphamide (CTD) can be used for relapsing / refractory disease.
Having a second high dose therapy
and stem cell transplantation (AuSCT)
In selected patients, a second transplant procedure may be an effective strategy, especially if they have had a good response to the first transplant and are in good health. In patients who have not had a prior stem cell transplant, high dose therapy and stem cell transplantation may be considered. High dose therapy steroid treatment with dexamethasone can be effective in controlling myeloma in patients who cannot have chemotherapy because of their general health, or in patients who have relapsed more than once following chemotherapy.
How does a patient know
if the treatment has worked?
The aim of treatment is to control the disease and its effects on the body. In order to find out how a patient responds to treatment, several tests will be carried out on a regular basis.
These tests may vary from patient to patient, but generally include regular blood and urine testing, bone marrow sampling and occasional x-rays or scans. The signs that treatment is working are a fall in the paraprotein level, less bone pain, improvement in anaemia and a reduction in the number of plasma cells in the bone marrow. However, one of the best indicators of response to treatment is an improvement in the general health of the patient.
In general terms, disease response is measured and categorised as in Table 6 Response Criteria. These criteria are defined using very specific standards, or criteria and are used in clinical trials to determine outcomes of treatments. It is important to note once again that the duration of response is as important as the level of response.
Table 6 – Response Criteria Outcomes based on criteria developed by the EBMT (European Group for Blood and Marrow Transplant) and IMWG (International Myeloma Working Group Uniform Response Criteria). Type of Response
Skeletal
Disease (on
Stringent complete
or urine; negative immunofixation test; normal free light chain ratio Complete
detectable in the blood +/- urine; negative immunofixation test Very good partial
detectable in the blood +/- urine, but positive immunofixation test, or 90% decrease Partial response
Minimal response
Stable disease (SD)
Not meeting the definition of minimal response or progressive disease Progressive disease >25% increase
lesions or increase in size of existing lesions Minimal Residual Disease (MRD)
Minimal residual disease is the name given to any remaining (residual) signs of myeloma following treatment that is not routinely visible through conventional measures and tests. It is increasingly thought that being able to assess MRD is key to predicting relapse in any individual patient and in time, will help direct more individual treatment plans. Methods being used to assess for MRD include specific genetic tests and improved scanning techniques. To read more about MRD see International Myeloma Foundation Black Swan Research Initiative at www.myeloma.org New treatments and clinical studies
There are many research projects looking to find more effective and less toxic treatments for myeloma. Many new treatments are in development and some of the most promising drugs are mentioned here.
However, until the effectiveness and safety of these treatments has been established, they are generally only considered for patients whose disease has progressed or returned after more established treatments. The best and safest way to take any new drug or treatment is as part of an approved clinical study. It is important to understand that not every patient is suitable for every new treatment but if patients are interested in trying a new treatment, this should be discussed with their doctor or nurse. Clinical studies are planned investigations, involving patients, designed to test new treatments or to compare different types of current treatment. They are run according to a strict set of guidelines called a protocol.
All patients involved in a study are closely monitored. The information collected during the course of the study is combined and analysed by trained researchers. The results will help to determine which are the best treatments and the most appropriate doses, to help improve care for patients in the future.
Being asked to participate in a clinical study does not necessarily mean being asked to try a new treatment. The study may be testing new ways of using current treatments. In some hospitals, treating cancer patients in clinical studies is part of standard practice.
What are the different types and phases of clinical studies?
These are studies carried out in the laboratory testing new ways of killing myeloma cells. The next step is to understand if the treatment dose can be delivered safely to patients. The only way of achieving this is to give increasing doses to laboratory animals and observe for side effects. Researchers test a new treatment in a small group of patients for the first time to evaluate safety, dosage range and identify side effects. It is not the aim of the study to identify whether a treatment works or not.
Larger studies in patients to look at the size of the response obtained and efficacy compared with previous standard treatments.
Phase III
Larger studies than phase II. They are randomised and compare the best current standard treatment with the new treatment. The new treatment will have been shown to be effective in the phase II study and the effect will be at least as good as and sometimes better than the best current standard treatment.
Studies carried out after the treatment has been introduced into everyday use. They continue to test treatment to collect information about its effects in various groups of patients and any side effects associated with long term use.
As more is discovered about experimental treatments, their role alongside the more established treatments will become clearer. In time, they are proved to be more effective and safer; they may replace some of the existing treatments. Because not all new treatments are better than standard treatments, it is important to carry out clinical studies to test these new treatments thoroughly.
What are some of the newer treatments
being explored in myeloma?
New approaches include: • Targeted treatments and monoclonal antibodies, which are intended to attack myeloma cells while leaving healthy cells alone.
• Vaccines, which try to boost the immune system's ability to attack myeloma cells.
• Increasing the ability of the immune system to recognise and kill myeloma • Ways to disrupt the myeloma cells' ability to divide.
• Ways of blocking messages within the bone marrow microenvironment that help to keep myeloma cells alive.
Table 7 – Novel drugs undergoing clinical trials Class of drug
Immune Modulators (IMiDs)
Carfilzomib (Kyprolis®) Denosumab (for bone disease) To find out more about clinical trials, what they are and what your participation may involve, contact the Cancer Council to obtain a booklet or download directly from their website Alternatively you can find range of information via Cancer Australia ‘Australian Cancer Trials' www.australiancancertrials.gov.au
Or the Australian and New Zealand Clinical Trials Registry (ANZCTR) Or for smart phone users in NSW, ACT and Vic search for ClinTrial Refer in the App Store for a frequently updated database of clinical trials in those states.
Living with myeloma
A diagnosis of myeloma affects everyone differently. At first it might be overwhelming, causing shock or a numb feeling. Information may not sink in at this point but don't worry, there will be many opportunities to ask more questions. Sometimes feelings may be controlled and at other times strong emotions may take hold. Some common reactions are fear, anger and frustration. These feelings are a natural part of coming to terms with the diagnosis. Learning more about myeloma, treatment options and life after myeloma treatment can help ease these feelings. It is also important to build good support networks for both patient and carer as effective communication can help to alleviate emotional stress.
Many patients experience depression and anxiety at some stage in their illness. It is not uncommon to feel optimistic at times and on other occasions to feel overwhelmed. Having difficulty sleeping, feeling irritable or experiencing a loss of interest in activities normally enjoyed, can be signs of increased anxiety or depression. It is important to recognise these symptoms and to discuss them with the doctor or nurse so that they can be managed effectively. Emotional support is important for living with myeloma. It is very easy for patients and family members to feel isolated, and strong emotions often make it difficult to discuss worries or fears. Talking to someone who understands what is happening can ease these feelings of isolation. Many people find that a specialist nurse is a good person to talk to. Contact the Myeloma Australia support line on the number below to talk to a myeloma support nurse in confidence. If finding emotions difficult to cope with, the doctor can make a referral to a counsellor or psychologist for help.
Support groups provide an informal and comfortable atmosphere in which members can share experiences and information. Many people assume that groups will be full of doom and gloom, but generally they are not. They are a supportive group of people who are facing the same things. Some support groups are run by patients and family members, others by healthcare workers or professional group facilitators. If there is not a myeloma group nearby, there may be a general cancer / haematology group that meets locally.
Call the Myeloma Australia support line, or ask the doctor or nurse if there is a myeloma support group nearby.
Family members can offer each other support by talking and listening. Being a good listener is an effective way to offer support and help ease anxiety of others. It is difficult to know how another person is feeling but trying to understand and empathising can help.
Counsellors offer the chance to explore feelings and experiences in a supportive, confidential environment. A counsellor does not give advice but helps find answers to the problems being faced.
Counselling may not always be available in the hospital but the specialist, nurse or GP will be able to recommend a professionally trained counsellor in the area. Alternatively the Australian Psychologists Referral Service can provide details of a local psychologist and can be contacted on 1800 333 497. Myeloma Australia holds regular Myeloma Patient and Family Seminars; they provide a great opportunity to meet and share experiences with other patients and carers as well as a team of myeloma experts. 1800 MYELOMA (693 566)
Allied health support
It is important to look after the whole body when living with myeloma and to seek the help of specialists when needed. If peripheral neuropathy is an issue, seeing a podiatrist can ensure the feet are cared for and kept free from injury or infection. Dietician:
If lack of appetite or taste changes are an issue, a dietitian can suggest strategies to maintain a balanced diet. Exercise physiologist or physiotherapist:
If fatigue is an issue, an exercise physiologist or physiotherapist can be used to design an exercise program to help increase energy levels.
There are many more services available and some of these may be provided through the hospital. If not, the Medicare Australia Chronic Disease Management Plan entitles those living with myeloma to five allied health visits per year. Consult the GP for access to the plan and a full list of services available.
Communication with the medical team
Good communication with the medical team will involve a lot of trust and collaboration. There should be no hesitation in asking them questions or discussing treatment options. Learning more about myeloma and the pros and cons of different treatments will help to communicate more easily with them. Any treatment decision should be reached together. Sometimes doctors and nurses forget that patients do not speak their medical language. If patients do not understand something they must say so! It is better that doctors and nurses explain it twice than for patients to go home confused and worried. Remember that the doctor may not be able to answer specific questions about the future. For example, predicting how successful a treatment will be. The doctor will probably be able to give average figures but these are not necessarily specific.
Tips:
• Have someone attend an appointment with you. This can help when recalling
what you've discussed with your health practitioner.
• Ask if it is possible to record the consultation to play back later. Some hospitals may offer this service for you. Write questions down and give a copy to the doctor at the beginning of each consultation.
• Carry a piece of paper or notebook to write down questions as they arise.
• Always divulge any medications or complementary treatments, such as vitamin supplements, bought at the chemist or supermarket as some can interact with myeloma medications (e.g. high dose Vit C and Green Tea should be avoided if taking bortezomib (Velcade®) therapy.) • Tell the doctor about any symptoms or side effects.
Questions for the doctor / medical team
Diagnosis
• What tests are needed?
• When will results be available?
• Is treatment necessary?
• What is it likely to be?
• Are the bones affected?• Are the kidneys affected?• Who will be the main point of contact at the hospital from now on? (Write their details in this guide) Treatment
• What are the treatment options?
• Is there a choice of treatment?
• What is the aim of this treatment?
• How successful has it been in the past?
• What would happen if treatment is delayed or denied?
• Is this treatment part of a clinical study?
• How experienced are you and your team in delivering this treatment?
• How is the treatment given, how long will it take?
• Will a hospital visit / stay be needed?
• What is it like before, during and after this treatment?
• Will there be side effects, when will they start and how long will they last?
• Will treatment affect the chance of having children in the future?
• What are the financial costs of this treatment?
• Will private health insurance cover the costs?
Post treatment
• How often are check ups and blood tests required?
• Are any other treatments e.g. bisphosphonates and maintenance
treatments required? • What are the signs that the myeloma has come back? Carers often have different information needs. Carers will want to know what they will need to do for the patient as they go through treatment.
• Will the patient require a stay in hospital and for how long?• Will the patient require a lot of looking after?• What kind of quality of life do you expect the patient to have?• Who can the carer call in an emergency? Self help checklist
Patients and carers
• Put aside time for relaxation
• Try to do one thing that brings enjoyment every day
• Recognise signs of stress or depression (feeling low, disturbed sleep,
headaches, lack of appetite) and bring them to the attention of the doctor • Learn about myeloma and its treatment – Many useful guides and websites • Join a support group; it can help to talk about feelings and experiences• Use the Myeloma Australia Support Line: Toll Free 1800 MYELOMA (693 566)• Find out from the GP, hospital doctor or nurse what services and benefits are available and ask for help if needed • Ask if there is a social worker at the hospital who can help apply for benefits• Ask for a contact name and number for a member of staff in the Haematology or Oncology department – Write it in this guide Patients
• Bring any side effects to the attention of the doctor
• Describe symptoms simply and accurately – Do not underplay or exaggerate
• Take all medication as directed – Use dosette boxes to help remember what • Try to drink three litres of water / liquid each day• Make getting enough sleep a priority• Think positively but allow for "off days"• Keep a diary of symptoms to help learn the pattern and remember to communicate them to the health care team Carers
• Take care of their own health
• Take some time each day for themselves, preferably out of house if possible
and away from the patient Further information and useful organisations
Myeloma Support Nurses 1800 MYELOMA (1800 693 566) Myeloma Australia – is a national nonprofit organisation dedicated to providing information and support for those affected by myeloma. Myeloma Australia raises awareness of the disease in the community, promotes research, advocates to governments for more generous support for the myeloma community and provides education, information and support to patients and carers through its specialist myeloma support nurses.
Clinical Practice Guideline – Multiple Myeloma.Myeloma Scientific Advisory Group (MSAG) 2012. Available via the MFA website. A guide for clinicians.
The Cancer Council of Australia
www.cancercouncil.com.au
Cancer Helpline 13 11 20 www.iheard.com.au – a site created by the Cancer Council to help dispel the myths and claims about cancer risks, prevention, screening and treatment. A national charitable organisation whose mission is to defeat cancer by building a cancer smart community. It aims to do this by focusing on six priority areas: research; patient support and information; cancer prevention and screening; advocacy; working in the community and fundraising. Provides a free and confidential telephone information and support service staffed by specialist cancer nurses. Also provides a range of other information resources and support programs including those delivered online or over the phone. The Leukaemia Foundation of Australia
www.leukaemia.org.au
Toll free 1800 620 420 A national nonprofit organisation dedicated solely to the care and cure of patients with leukaemia, lymphoma, myeloma and related blood and marrow disorders. They provide a range of support services that includes the provision of information, education, support, accommodation and transport.
Toll free: 1800 242 636 An Australian Government initiative, Carers Australia represents the needs and interests of carers at a national level. For information and support carers can call the Commonwealth Carer Resource Centre in their state or territory. A comprehensive information kit is available along with a variety of fact sheets available online.
NSW Government agency dedicated to the control and cure of cancer through prevention, detection, innovation, research and information. eviQ – Cancer Treatments Online – provides information for patients, carers and families with a suite of resources, useful websites and high quality, current evidence based treatment information. www.eviQ.org.au Palliative Care Australia
The peak national organisation representing the interests of all of those who share the ideal of quality of care at the end of life. Produces a range of information resources available to download direct from the website.
Myeloma-Specific International Information Resources
International Myeloma Foundation (IMF)
www.myeloma.org
Email: [email protected]: 001 818 487 7455 An International charitable organisation that informs and supports those affected by myeloma whilst supporting medical research through the Black Swan Research Initiative and advocating at multiple levels for those affected by myeloma. Amongst other support programs they provide a comprehensive range of patient information material, newsletter and video clips available to download from their website.
E-mail: [email protected]: +4 131 556 9720 A UK based charity that informs and supports people affected by myeloma, and helps to improve standards of treatment and care through education and research. Amongst other programs they provide a comprehensive range of patient information material available to download on line; educational video clips via Myeloma TV and an e-newsletter ‘Myeloma Matters. Multiple Myeloma Research Foundation (MMRF)
www.themmrf.org
Email: [email protected]: +203 972 1250 The MMRF pursues innovative means that accelerate the development of next generation multiple myeloma treatments to extend the lives of patients and lead to a cure. A charitable organisation that also provides a comprehensive range of information for those affected by myeloma, produces a newsletter and hosts a range of educational activities both online and in person. Other Useful Organisations
Blood and transplant network NSW Australian Bone Marrow Donor Registry Arrow Bone Marrow Transplant Foundation Australian Government Department of Health and Ageing Australian Red Cross Blood Service Australian Physiotherapy Association Commonwealth Respite and Carelink Centre Kidney Health Australia Medicare Australia National Prescribing Service Macmillan Cancer Support American Cancer Society US National Cancer Institute The National Cancer Institute (USA) National Centre for Complementary and Alternative Medicine About Herbs – Memorial Sloan Kettering Medical Terms Explained
Albumin: Major protein found in the blood. A patient's albumin level can
provide some indication of overall health and nutritional status.
Alkylating Agent: A chemotherapeutic agent such as melphalan or
cyclophosphamide. Alkylating refers to the way in which these agents cross
link the DNA of myeloma cells and block cell division.
Allogeneic stem cell transplantation: A procedure in which stem cells or
bone marrow from a compatible donor (usually a family member) are collected
and given to the patient after high dose chemotherapy treatment.
AL Amyloidosis: A condition in which myeloma light chains (Bence Jones
proteins) are deposited in tissues and organs throughout the body. This occurs
more commonly with lambda versus kappa Bence Jones proteins. In patients
with amyloidosis, the light chain proteins bind to certain tissues such as
heart, nerves and kidney rather than being excreted out of the body through
the kidneys.
Anaemia: A decrease in the normal number of red blood cells, or the
haemoglobin that they contain, usually below 10g/dl with over 13-14g/dl being
normal. Myeloma in the bone marrow blocks red cell production, leading to
shortness of breath, weakness, and tiredness.
Angiogenesis: Blood vessel formation, which usually accompanies the growth
of malignant tissue, including myeloma.
Antibiotics: Drugs used to treat infection.
Antibody: A protein produced by certain white blood cells (plasma cells) to
fight infection and disease in the form of antigens such as bacteria, viruses,
toxins, or tumours. Each antibody can bind only to a specific antigen. The
purpose of this binding is to help destroy the antigen. Antibodies can work
in several ways, depending on the nature of the antigen. Some antibodies
disable antigens directly. Others make the antigen more vulnerable to
destruction by other white blood cells. In myeloma there is overproduction of
non functional antibodies.
Antigen: Antigens are molecules on the surface of cells that the immune system
recognises.
Apheresis: A procedure in which stem cells are collected from the blood
using a machine which separates them out, returning the remaining blood
components to the donor.
Apoptosis: A normal cellular process involving a coordinated series of events
leading to the controlled death of a cell.
Aspiration: The process of removing fluid or tissue, or both, from a specific
area in the body.
Asymptomatic myeloma: See smouldering myeloma
Autologous stem cell transplant: A procedure in which a patient's own
stem cells are collected, stored and then given back following high dose
chemotherapy.
Bence Jones: A myeloma protein present in urine. The amount of Bence Jones
protein is expressed in terms of grams per 24 hours. Normally a very small
amount of protein (<0.1g/24h) can be present in the urine, but this is albumin
rather than Bence Jones protein. The presence of any Bence Jones protein is
abnormal. See also light chain.
Beta 2 Microglobulin (ß M): A small protein found in the blood. High levels
occur in patients with active myeloma. Low or normal levels occur in patients with early myeloma and / or inactive disease. Approximately 10% of patients have myeloma that does not produce ß2M. For these patients, ß2M testing cannot be used to monitor the disease. At the time of relapse, ß2M can increase before there is any change in the myeloma protein level. Therefore, 90% of the time, ß2M is very useful for determining disease activity.
Biopsy: The removal of a sample of tissue for microscopic examination to aid
in diagnosis.
Bisphosphonate: A type of drug that binds to the surface of bone where it
is being resorbed (or destroyed) to protect it. They include zoledronic acid
(Zometa®), pamidronate (Aredia®) and clodronate (Bonefos®). In myeloma, they
are used to treat bone disease and protect against further damage.
Blood cells: Minute structures produced in the bone marrow; they include red
blood cells, white blood cells, and platelets.
Blood count: The number of red blood cells, white blood cells, and platelets in
a sample of blood.
Bone marrow: The soft, spongy tissue in the centre of bones that produces
white blood cells, red blood cells, and platelets.
Bone marrow aspiration and trephine (BMAT): The removal, by a needle,
of a sample of fluid and bone from the bone marrow for examination under
a microscope.
Calcium: A mineral important in bone formation. High levels of calcium in the
blood can occur when there is bone destruction.
Catheter: A tube that is placed in a blood vessel to provide a pathway for
treatment with drugs or nutrients. Used during prolonged repeated treatment,
a Central Venous Catheter is special tubing that is surgically inserted into a
large vein near the heart and exits from the chest or abdomen. The catheter
allows medications, fluids, or blood products to be given and blood samples
to be taken.
Cell proliferation: An increase in the number of cells as a result of cell growth
and cell division.
Chemotherapy: The treatment of cancer with drugs that kill rapidly dividing
cells.
Chromosome: A strand of DNA and proteins in the nucleus of a cell.
Chromosomes carry genes and transmit genetic information when cells divide.
Normally, human cells contain 46 chromosomes.
Clinical trial: A research study of new treatment that involves patients. Each
study is designed to find better ways to prevent, detect, diagnose, or treat
cancer and to answer scientific questions.
CRAB: The acronym given to the criteria to help guide doctors in their
decisions to start treatment. Calcium elevation; Renal insufficiency; Anaemia;
Bone disease.
C-reactive protein (CRP): A protein produced by the liver when there is an
inflammatory process occurring in the body. The level of CRP in the blood can
be raised in various inflammatory diseases, such as infections, and cancers,
including myeloma.
Creatinine: A small chemical compound normally excreted by the kidneys.
If the kidneys are damaged, the level of creatinine builds up, resulting in an
increased serum creatinine. The serum creatinine test is used to measure kidney function.
CT or CAT (Computerised Tomography) scan: A test using Computerised X-rays
to create three dimensional images of organs and structures inside the body,
used to detect small areas of bone damage or soft tissue involvement. Also
called CAT (Computed Axial Tomography) scan.
Cytokine: A substance secreted by cells of the immune system that stimulates
growth / activity in a particular type of cell.
Cytogenetics: A laboratory test on plasma cells to determine if there are any
abnormalities in the chromosomes.
DEXA Scan (Dual Photon X-ray Absorptiometry) study: The best measure
of bone density. Used to reveal amount of bone loss.
Dexamethasone: A powerful steroid given alone or with other drugs.
Dialysis: When a patient's kidneys are unable to filter blood, the blood is
cleaned by passing it through a dialysis machine.
DNA: Or deoxyribonucleic acid, is the hereditary material in humans and almost
all other organisms.
Electrophoresis: A laboratory test in which a patient's serum (liquid portion
of blood) or urine molecules are subjected to separation according to their
size and electrical charge. For myeloma patients, electrophoresis of the
blood or urine allows both the calculation of the amount of myeloma protein
(M-protein) as well as the identification of the specific protein type (M-spike)
characteristic for each patient. Electrophoresis is used as a tool both for
diagnosis and for monitoring.
Engraftment: The process by which transplanted stem cells travel to the
recipient's bone marrow where they will begin to grow and develop into new
blood cells. During this time the number of red cells, white cells and platelets in
the blood may be lower than normal.
Enzyme: A substance that affects the rate at which chemical changes take
place in the body.
Erythrocytes: Red blood cells (RBCs). RBCs carry oxygen in the form of
haemoglobin to body cells and carry carbon dioxide away from body cells.
Erythropoietin(EPO): A hormone produced by the kidneys. Myeloma
patients with damaged kidneys don't produce enough erythropoietin and
can become anaemic. Injections with synthetic erythropoietin can be helpful.
Blood transfusion is another alternative, especially in an emergency. Synthetic
erythropoietin is being used prophylactically before chemotherapy and as a
supportive therapy after chemotherapy to avoid anaemia.
FISH: Fluorescent In-situ hybridisation.
Free Light Chains: See serum free light chains.
Graft versus host disease (GvHD): A complication of allogeneic transplants
whereby the donor cells (the graft) recognises the recipient's body (the host) as
foreign and mounts an attack. This can cause skin, liver and gut problems, and
is usually treated with steroids that suppress the immune system.
Growth factor (G-CSF): Granulocyte Colony Stimulating Factor is a protein
used to promote white cell production in the bone marrow. It is given as an
injection into the skin (sub cutaneous).
Heavy Chain: See immunoglobulin.
Hypercalcaemia: A higher than normal level of calcium in the blood. This
condition can cause a number of symptoms, including loss of appetite, nausea,
thirst, fatigue, muscle weakness, restlessness, and confusion. Common in
myeloma patients and usually resulting from bone destruction with resultant
release of calcium into the blood stream. Often associated with reduced
kidney function since calcium can be toxic to the kidneys. For this reason,
hypercalcaemia is usually treated on an emergency basis using intravenous
fluids combined with drugs to reduce bone destruction and direct treatment
for the myeloma.
Immunoglobulin (Ig): A protein that is produced by plasma cells for a variety
of purposes, most commonly to fight infection. There are five main types; IgA,
IgD, IgE, IgG and IgM. See also antibody.
Immunosuppression: Lowering the number or activity of cells that make
up the immune system, primarily the white cells. Suppression of the immune
system can mean an increased risk of infection.
Informed Consent: The process requiring a doctor to give a patient enough
information about a proposed procedure for the patient to make an informed
decision about whether or not to undergo it. The doctor must, in addition to explaining all procedures, address the issues of risks, benefits, alternatives, and potential costs.
Interferon: A naturally produced hormone (cytokine) released by the
body in response to infection or disease, which stimulates the growth of
certain disease fighting blood cells in the immune system. Interferon can be
artificially synthesised and used as a form of immunotherapy, primarily in the
maintenance (plateau) phase to block any regrowth of myeloma and thus
delay or prevent relapse.
Kappa: See light chain.
Lambda: See light chain.
Lesion: An area of abnormal tissue change. A lump or abscess that may be
caused by injury or disease, such as cancer. In myeloma, "lesion" can refer to a
plasmacytoma or a hole in the bone. See lytic lesion.
Leucocytes: Cells that help the body fight infections and other diseases. Also
called white blood cells (WBCs).
Leukopenia: A low number of white blood cells.
Light chain: One of the short protein chains that make up an immunoglobulin
molecule. May be referred to as kappa or lambda type. Light chains produced
by myeloma cells are also referred to as Bence Jones proteins after the man
who first identified them.
Lymphocytes: A type of white blood cell that fights infection and disease.
Lytic lesions: The damaged area of a bone that shows up as a dark spot on
an X-ray when enough of the healthy bone in any one area is eaten away.
Lytic lesions look like holes in the bone and are evidence that the bone is
being weakened.
M proteins (M spike): Antibodies or parts of antibodies found in unusually large
amounts in the blood or urine of myeloma patients. M spike refers to the sharp
pattern that occurs on protein electrophoresis when an M protein is present.
Synonymous with monoclonal protein, paraprotein and myeloma protein.
MRI (Magnetic resonance imaging): An imaging technique that provides
detailed images of bone and soft tissue.
MGUS: Monoclonal Gammopathy of Undetermined Significance is a pre-
malignant disorder characterised by the accumulation of plasma cells
within the bone marrow and the presence of a monoclonal protein spike on
electrophoresis. The feature that distinguishes it from myeloma is the lack of
end organ damage. What this means is that there are no lytic bone lesions,
no renal damage and no anaemia. The condition is stable and requires no
treatment, only monitoring. By 10 years of follow-up approximately 10-20% of
patients progress to clinical myeloma.
Mini-allogeneic transplant: A type of allogeneic transplant that uses lower
doses of chemotherapy than a standard allogeneic transplant, and avoids
some of the side effects and risks associated with higher dose chemotherapy.
Mobilisation: The process by which the number of stem cells in the bone
marrow is increased so that they ‘spill over' into the blood stream and can
be collected.
Monoclonal: A clone or duplicate of a single cell. Myeloma develops from
a single malignant plasma cell (monoclone). The type of myeloma protein
produced is also monoclonal; a single form rather than many forms (polyclonal).
The important practical aspect of a monoclonal protein is that it shows up as a
sharp spike (M spike) in the serum electrophoresis test.
Mucositis: Inflammation of the lining of the digestive tract, often seen as
soreness of the mouth. Can occur as a side effect of chemotherapy.
Myeloma Related Event (MRE): Criteria used by doctors to help decide when
treatment should begin. Often used interchangeably with the acronym CRAB.
Neoplasm: A new growth of tissue or cells; a tumour that can be referred to as
benign or malignant.
Neutrophils: A type of white blood cell (leucocyte) necessary to combat
bacterial infection.
Neutropenia: A low number of neutrophils in the blood, which can lead to
an increased risk of infection. Can be caused by the myeloma itself or as a
side effect of treatment, particularly chemotherapy. Sometimes treated with
a growth factor that can boost the number of neutrophils (G-CSF). See
Osteoblast: Bone forming cells.
Osteoclast: Cells that resorb or break down bone. Found in the bone marrow
at the junction between the bone marrow and the bone. In myeloma, the
osteoclasts are over-stimulated while osteoblast activity is blocked. The
combination of accelerated bone resorption and blocked new bone formation
results in lytic lesions.
Osteonecrosis of the jaw (ONJ): A condition in which regions of the bones
of the jaw fracture and do not heal properly, causing ongoing, sometimes
painful, complications.
Palliative treatment/care: Aimed at improving the quality of life by relieving
pain and symptoms of disease but not altering its course.
Paraprotein: See M protein.
Pathological fracture: A break in a bone usually caused by cancer or some
disease condition. Occurs in myeloma-weakened bones which can't bear
normal weight or stress.
PET (Positron Emission Tomography) Scan: A diagnostic test that uses a
sophisticated camera and computer to produce images of the body. PET scans
can show the difference between healthy and abnormally functioning tissues.
Peripherally Inserted Central Catheter (PICC): A small tube (catheter)
inserted into a small blood vessel in the arm that extends into a larger blood
vessel in the chest. Used as a longer term device to enable the administration of
intravenous drugs and blood products. Can remain in place for many months
and reduces the need for repeated cannulation (insertion of small, disposable
needle, lasting < 72 hours). See also catheter.
Plasma: The liquid part of the blood in which red blood cells, white blood cells,
and platelets are suspended.
Plasma cells: Special white blood cells that produce antibodies. The
malignant cell in myeloma. Normal plasma cells produce antibodies to fight
infection. In myeloma, malignant plasma cells produce large amounts of
abnormal antibodies that lack the capability to fight infection. The abnormal
antibodies are the monoclonal protein, or M protein. Plasma cells also produce
other chemicals that can cause organ and tissue damage (i.e. anaemia, kidney
damage, and nerve damage).
Plasmacytoma: A collection of myeloma plasma cells found in a single
location rather than diffusely throughout the bone marrow, soft tissue, or bone.
Plasmapheresis: The process of removing certain proteins from the blood.
Plasmapheresis can be used to remove excess antibodies from the blood of
multiple myeloma patients.
Platelet: Small cell fragments in the blood that helps it to clot. Also called
thrombocytes.
Radiation therapy (Radiotherapy): Treatment with X-rays, gamma rays,
or electrons to damage or kill malignant cells. The radiation may come from
outside the body (external radiation) or from radioactive materials placed
directly in the tumour (implant radiation).
Red blood cells (RBC): See erythrocytes.
Reduced intensity conditioning (RIC): Lower doses of chemotherapy or
radiation prior to an allogeneic transplant. This regime is less toxic and more
easily tolerated than full intensity conditioning.
Related Organ Tissue Injury (ROTI): An acronym describing specific
impairments to the optimal functioning of the body that help doctors decide
when treatment should begin. The term is used interchangeably with MRE
and CRAB.
Serum: Liquid portion of blood remaining after blood has been allowed to clot
and the clot removed.
Serum Free Light Chains (SFLC): A portion of the monoclonal protein of light
molecular weight that can be measured in a sensitive assay, the Freelite™ test.
Sestamibi scan: Is a scanning technique using an injection of a radiolabelled
isotope to help detect myeloma deposits that may not be detected by other
imaging techniques.
Skeletal survey (bone survey): A series of X-rays of the skull, spine, ribs, pelvis
and long bones to look for lytic lesions and/or osteoporosis.
Smouldering myeloma: In this condition there is evidence of plasma cells
in the bone marrow and a measurable paraprotein with minimal end organ
damage. These levels are not stable and will eventually progress to myeloma.
Conventionally, treatment is withheld until there is significant evidence of
disease progression.
Stem cells: The immature cells from which all blood cells develop. Normal
stem cells give rise to normal blood components, including red cells, white
cells, and platelets. Stem cells are normally located in the bone marrow and
can be harvested for transplant.
Thrombocytopenia: A low number of platelets in the blood. The normal level
is 150,000 - 250,000. If the platelet count is less than 50,000, bleeding problems
could occur. Major bleeding occurs when the platelet count is 10,000 or less.
Vertebroplasty: The injection of surgical cement into the vertebral space to
reduce the pain caused by vertebral compression fracture.
Waldenström's macroglobulinaemia: Not a type of myeloma. A rare type of
indolent lymphoma that affects plasma cells. Excessive amounts of IgM protein
are produced.
White blood cells: See leucocytes.
Appendix 1: Table of commonly used medications
IV Intravenous
O Oral
SC Subcutaneous
Drug Name
Trade Name
Anti myeloma drug belonging to a group of drugs called proteasome inhibitors Anti myeloma drug undergoing research in clinical trials.
Bisphosphonate drug. Protects bones from further damage by myeloma cells.
Anti myeloma chemotherapy drug. Often in combination with other anti myeloma drugs Anti myeloma drug. Often in combination with other anti myeloma drugs Anti myeloma drug. Often in combination with other anti myeloma drugs Granulocyte
A protein that stimulates the development colony stimulating
and growth of white blood cells. Used to stimulate the growth of stem cells before harvesting for transplantation or to boost white cells if they are reduced in number
Pegfilgrastim
Anti myeloma chemotherapy drug given in combination with other anti myeloma drugs.
Anti myeloma drug chemically similar to thalidomide, lenalidomide is a 2ndgeneration immunomodulatory drug (IMiD) that works by affecting and modifying the immune system. The exact way in which IMiDs work is not yet fully understood and it is thought they have multiple mechanisms of action.
Anti myeloma drug. Given in combination with other anti myeloma drugs or in high dose intravenously as part of the stem cell transplant process.
Anti nausea medication. Often given as tablets to help prevent nausea associated with medications Oxycodone
Pain medication.
Bisphosphonate drug. Given intravenously to protect bones from further damage by myeloma cells.
3rd generation immunomodulatory drug (IMiD) that works by affecting and modifying the immune system. The exact way in which IMiDs work is not yet fully understood and it is thought they have multiple mechanisms of action.
1st generation immunomodulatory drug (IMiD) that works by affecting and modifying the immune system. The exact way in which IMiDs work is not yet fully understood and it is thought they have multiple mechanisms of action.
Appendix 2: Tests and investigations
Bone marrow biopsy
This is the single most critical test to determine the percentage of myeloma cells in the bone marrow. For solitary plasmacytoma, direct biopsy of the tumour mass is often performed.
Special testing is done to assess
Chromosome analysis (cytogenetic testing) prognosis (e.g. chromosomes,
can reveal good or poor chromosome immune typing, staining for
features using direct and / or fluorescent in situ hybridization (FISH) analysis.
1. Full blood count
• To assess presence / severity of anaemia• To assess for low white cell count• To assess for low blood platelet count 2. Chemistry panel
• Particularly important to assess kidney function (creatinine), calcium level and lactate dehydrogenase (LDH) 3. Special protein testing
This shows the presence of the abnormal Serum protein electrophoresis
(SPEP), Serum Free Light Chain
• The amount of abnormal M protein as (SFLC), immunoelectrophoresis
well as the normal albumin protein level • Shows the type of M protein • SFLC testing can be used to measure the amount of free Kappa or Lambda protein Shows the presence, amount, and type of Special protein testing
abnormal myeloma protein in the urine as for the blood:
Bone imaging
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 using a series of X-rays is needed to show loss or thinning of bone, 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 Whole Body FDG / PET (fluoro-
A much more sensitive whole body scanning deoxyglucose positron emission
technique currently being investigated for its usefulness for disease monitoring, especially for non-secretory disease.
A scanning technique that uses a small amount of radioactive material (radiotracer) to help find myeloma deposits that are not found using other scanning techniques. Not a common test for myeloma. Appendix 3: Blood tests
Blood tests
Test Name
Full Blood
A low count makes the body less able to fight infection A low haemoglobin is also anaemia, causing fatigue A low haemoglobin is also anaemia, causing fatigue A low count makes the body bruise or bleed easily Measure of kidney function creatinine and
Measure of kidney function Raised by myeloma bone disease Often lowered in myeloma because of presence of paraprotein Often raised in myeloma because of amount of paraprotein Abnormal protein found in several conditions, including myeloma.
The normal range is an average: each hospital laboratory has its own ‘normal range' of values.
Explanation of units
• g/dl how many grams there are in a decilitre (one tenth of a litre) of blood• g/l how many grams there are in a litre of blood• x109/l how many thousand million cells there are in a litre of blood• x1012/l how many million million cells there are in a litre of blood• mmol/l how many thousandths of a mole** in a litre of blood• umol/l how many millionths of a mole** there are in a litre of blood**mole a standard molecular measurement for the amount of any chemical Note: Doctors do not use a litre of blood to make these measurements; they just take a small sample (a few millilitres) and then multiply the results.
Appendix 4: Staging Systems
International Staging System (ISS)
Serum albumin ≥3.5g/dL ß M of <3.5mg/L ß M<3.5mg/L and albumin <35g/L or ß M 3.5 – 5.5mg/L Stage III
Serum ß M of ≥5.5mg/L Functional Criteria – ‘CRAB'
Calcium elevation Renal (kidney) insufficiency/failure Bone abnormalities/disease (lytic lesions or bone loss) I wish to make a Donation
Please complete and post to:
Appeals Manager
Myeloma Foundation of Australia Inc

PO Box 5017
BURNLEY, Victoria 3121
Head Office: 335 Swan Street, RICHMOND, Victoria 3121
Tel: (03) 9428 7444 Fax: (03) 9428 4844 Toll Free: 1300 632 100
Mr/Mrs/Ms/Dr/Prof (other) . (First name) .
. PostCode: .
Phone: ( ) .
Please find enclosed my Gift of $ .
Payment Method: Receipt Required Name on Card: .
Cheques to be made payable to "Myeloma Foundation of Australia Inc"
Myeloma Australia is a trading name of The Myeloma Foundation of Australia Inc.
Strict confidentiality will be observed with any information provided. Gifts of $2.00 and over are tax deductible. A Limited Liability Incorporated Association Incorporated in Victoria, CAV No. AA00379711V ARBN: 126 035 247 ABN: 30 476 390 368 Fill in your contact details and those of the key health professionals involved in your care. You may like to include numbers for working hours and out of hours hospital contacts.
Hospital medical registration number (if known): Haematologist / Oncologist: _ Treatment centre: _ During working hours Tel no: Out-of-hours Tel no: _ Nurse Specialist / Coordinator:

To discuss any of the information contained in this guide, or further assistance, please call the Myeloma Support Line on 1800 MYELOMA (1800 693 566) A Myeloma Support Nurse will answer your call in confidence Publication date: August 2014 toll free: 1300 632 100
myeloma support line: 1800 693 566
Myeloma Australia PO Box 5017, Burnley, Vic 3121 Myeloma Australia is a trading name of Myeloma Foundation of Australia Inc.
This publication is supported by an educational grant by Janssen.
All content in this publication has been independently prepared by Myeloma Australia

Source: http://myeloma.org.au/wp-content/uploads/sites/2/2015/10/73378-Myeloma-Booklet-LowRes.pdf