I've Just Been Diagnosed. with Multiple Myeloma, What s Next?

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1 I've Just Been Diagnosed with Multiple Myeloma, What s Next?

2 Table of Contents Message from a Survivor Introduction What is Multiple Myeloma? What Causes Multiple Myeloma? Genes & Multiple Myeloma What Tests Help Evaluate the Presence of Cancer and its Extent (Stage). Staging of Multiple Myeloma Treatment Options for Multiple Myeloma Use of Bisphosphonates Clinical Trials Glossary

3 Message from a survivor I t all began in early 2005 with aching in my lower back and difficulty standing. When my primary care physician did a reflex check on my left knee and there was no reaction, he ordered an MRI. The MRI showed that there was a tumor in my spine. Upon consulting with a Neurosurgeon it was determined that I had plasmacytoma, which can be a precursor for Multiple Myeloma. I had a Kyphoplasty which inserted rods in my back to keep my spine from collapsing when I had radiation to shrink the tumor. After Kyphoplasty and radiation, my Oncologist monitored me for changes that would indicate the Multiple Myeloma was increasing. In the meantime, my husband and I did extensive research to learn more about Multiple Myeloma. Almost five years had passed and I thought it was over. In 2009 the protein indicator of Multiple Myeloma started increasing and my Oncologist suggested that a stem cell transplant would be most effective to put it in deep remission. After research about stem cell transplants, we decided that an autologous stem cell transplant would be most effective. In March, 2010, on the day I was scheduled to start the transplant process, I was diagnosed with shingles in my right foot which lasted for two months. During that time my faith stood strong and kept me hopeful. In July 2010 my stem cells were harvested and in January 2011 I had my transplant. The transplant was to be done on an outpatient basis; however, I started running a fever right after the transplant and was admitted immediately into the hospital. While there I had pneumonia. My husband and the doctor were in constant communication. The doctors and nurses were all just great in caring for me. I made it home to stay finally in early February and had to wear a mask when I went out. One hundred days is the benchmark time when you should start to feel more like yourself after a transplant. During that time I had to learn to pace myself and rely on my husband as my caregiver. Educate yourself and your caregiver about your illness, have a doctor you feel comfortable with, have a positive attitude and faith that God is in control. Introduction T his brochure will help you get through the first hours and days after learning that you have multiple myeloma. It contains basic information that will help you ask the questions you may need to ask and start thinking about what to do next. The brochure will direct you to reliable information about multiple myeloma and current ways to manage the disease. Who We Are Copyright 2012 by Alamo City Cancer Council Author: Sharon T. Wilks, M.D., F.A.C.P. The Alamo City Cancer Council (ACCC) is a non-profit organization based in San Antonio, Texas. It works with the representatives from organizations in Bexar County that focus on needs of individuals afflicted with cancer. The ACCC wishes to thank all of those individuals who support this organization and its mission in helping educate those who are diagnosed with cancer. Please visit the ACCC website: Flo San Antonio, Texas 2 3

4 What is Multiple Myeloma? This is a form of a blood cancer that is a malignant growth of a type of white blood cell known as a plasma cell. It is known as a blood cancer as these cells arise from the bone marrow. This process leads to interference of normal functions including new formation of blood cells. This condition leads to altered production of antibodies (immunoglobulins) that are normally produced by plasma cells. When a single clone (group) of plasma cells are aberrant (abnormal growth), one large amount of abnormal immunoglobulin is produced known as an M or monoclonal protein. Complications of this disease can lead to destruction of the skeletal system (bone) which can lead to fractures, hypercalcemia (increased serum/blood calcium), anemia (low red blood cells), impaired kidney function and increased risk of infection due to immunodeficiency. What Causes Multiple Myeloma? There is no known cause of multiple myeloma for the majority of cases. However, there are some risks that are associated with the development of this disease such as radiation exposure, chronic antigen stimulation (stimulation of the immune system to fight chronic infections), environmental exposures including formaldehyde, wood & paper products, Agent Orange, hair dyes, paint, asbestos and benzene. Other risks include exposure to viruses including Herpes virus. This disease is not inherited. However, there are many reports of this disease occurring in more than one member of the same family. Genes & Multiple Myeloma Plasma cell, a type of white blood cell. It is not uncommon to have changes in the gene patterns in patients who are diagnosed with this condition. Many of the changes can be complex. Many studies have shown that a transference of gene information involving chromosome 14 which has the site for the immunoglobulin heavy chain. The most common changes in the chromosomes include chromosome 3, 4, 11, 14. Poor risk groups with associated gene abnormalities include changes in chromosomes including 3, 4, 11, 13 & 14. Fortunately, with use of newer drugs, even patients that acquire these changes can still enjoy a long remission. What Tests Help Evaluate the Presence of Cancer and its Extent (Stage)? Complete Blood Count (CBC) - this is a blood test that measures the content or amount of white blood cells, red blood cells and platelets (blood cells that help us clot). Serum Protein Electrophoresis (SPEP) - this is a blood test that shows a pattern of proteins that can help with diagnosis and monitoring of the plasma cell production of the monoclonal protein (M protein). Urine Protein Electrophoresis (UPEP) - the same study as the SPEP but tested on the urine from a collection of urine for 24 hours. Serum Immunoglobulins (IGG's) - this is a blood test that measures the concentration of the immunoglobulins in the blood. Individuals with multiple Typical appearance of cells seen on bone marrow aspiration. An increased number of plasma cells are present. myeloma may produce lower amounts (hypogammaglobulinemia) due to overproduction of a clone of protein also known as the M protein. Immune electrophoresis (IEP) - a blood test that determines the exact heavy and/or light chain type of the M protein. Serum B2 Microglobulin - a test of the blood that is a part of the light chain for human leukocytes. Skeletal Survey - this is a series of plain x-rays that evaluate for changes in the bones that are typical of multiple myeloma. These changes are called lytic bone disease which look like dark circles on a plain x-ray. Bone Marrow Biopsy - this is a procedure that involves a physician using a needle removing marrow from the pelvis and/or sternum. This gives the percent of plasma cells that can be critical for the diagnosis of multiple myeloma. See figure on page

5 Staging of Multiple Myeloma The main system that has been used for years for determining the extent of disease is known as the Durie-Salmon staging system. This system includes the values of hemoglobin, serum calcium level, M- component production including the concentration of immunoglobulins, the Bence Jones protein concentration, the presence or absence of lytic bone disease. A subclassification includes renal function status. See the table below for the staging classifications. Durie-Salmon Staging System Stage Criteria International Staging System (ISS) This is a newer staging system for multiple myeloma that is being used more often by clinicians though it may not be as accurate for determining tumor burden as the Durie-Salmon system of staging. Stage I II Criteria B2 Mirogolbulin <3.5 mg/l and Serum Albumin >3.5 Not fitting stage I or III I II Hemoglobin >10 g/dl Serum calcium level<12 mg/dl Normal bone or solitary plasmacytoma on x-ray Low M-component production rate: IgG <5 g/dl; IgA <3 g/dl, or Bence jones protein < 4g/24 hours Not fitting stage I or III III Prognostic Factors B2 Microgoblulin >5.4 mg/l There are various factors that have been noted to predict for a more poor outcome as it relates to surviving with multiple myeloma. Simply put, patients who are sicker do less well and tolerate treatments less well. III Hemoglobin <8.5 g/dl Serum calcium >12 mg/dl Multiple lytic bone lesions on x-ray High M-component production rate: IgG >7g/dL, IfA>5 g/dl or Bence Jones protein >12 g/24 hours Subclassification: Normal renal function (serum creatine <2 mg/dl)=a Abnormal renal function (serum creatinine >2 mg/dl)=b Suggested factors include: Overall condition with performance function of 3 or 4 Low serum albumin <3 g/dl Renal dysfunction with a serum creatinine >2 mg/dl Low platelet count <150,000 Age >70 years of age Beta 2 Microgulin level > 4 mg/l Plasma cell labeling Index >1 percent Hemoglobin <10 g/dl Bone marrow plasmacytosis >50% 6 7

6 Treatment Options for Multiple Myeloma As this disease is a form of blood cancer, there is no routine role of surgery for this condition. Radiation can be used if bone pain occurs and can relieve symptoms significantly. It is less useful for overall disease control. Thus, the mainstay of treatment involves chemotherapy which can come in the form of oral (pill) or intravenous (infusion of medicines into the vein). The treatment options for this disease continue to evolve but the description of treatment in this segment reviews current approaches in management. First Phase of Treatment Conventionally, treatment in this phase will incorporate two or more drugs usually containing an alkylator and steroid for an attempt to reduce the volume of cancer cells more briskly. Typical options include Bortezemib (Velcade ), Dexamethasone (Decadron ), Cyclophosphamide (Cytoxan ), Thalidomide (Thalomid ), Leno- lidamide (Revlimid ), Doxorubicin (Adriamycin ), Doxorubicin Liposome (Doxil ) and Vincristine (Oncovin ). These treatments may be given one or more times a week several weeks a month for several months. If the disease appears to respond, this effect is often not durable and so in order to improve survival rates of patients with multiple myeloma, it is felt necessary to follow the initial phase of therapy with transplantation while this disease is responsive. Stem Cell Transplantation (Bone Marrow Transplantation) Currently, improved survival rates have been seen amongst patients who undergo this form of treatment early in the phase of diagnosis than seen in patients who undergo this form of therapy later in the course of the disease. Typically the source of stem or bone marrow cells that are used are taken from the patient (autologous) though some reports suggest a possible role for patients to receive these cells from a donor (allogeneic or syngeneic transplantation). Stem cells are collected via a pheresis unit that collects these cells from the blood of patients where only the stem cells are reserved in a sterile collection device which contains preservative that upon storage allows these cells to remain viable for many years. These cells are kept sterile and frozen until the time the cells need to be administered for a patient after they have received high doses of chemotherapy and/or radiation treatments. Bone marrow cells can be obtained through a harvesting procedure and sterilized and preserved in a similar fashion The area over the posterior hip is located and cleaned for access of the bone marrow. Hipbone Biopsy needle Bone marrow aspiration Marrow A special needle is inserted via sterile technique through the skin and bone to allow for aspiration of marrow. 8 9 Skin

7 Stem Cell Transplantation cont. as the process for stem cell collection. It is felt that the high doses of chemotherapy and radiation given prior to receipt of the stem or bone marrow cells leads to a more complete clearance of residual cancer cells that still survive the first phase of therapy. Many patients who undergo transplantation can be placed into a complete remission (a state where there is no evidence of cancer present). Maintenance Therapy Recently, there have been reports suggesting a significant improvement in delaying relapses (cancer reoccurrence) by use of maintenance therapy with use of a drug known as Revlimid. This is a drug that comes in pill form and is taken daily and has fewer side effects and may allow for longer remission status. Most chemotherapy drugs have similar side effects including nausea, vomiting, hair loss, fatigue and low blood counts that can lead to infection and bleeding risk. Other common side effects from these treatments include neuropathy (numbness/tingling sensation) of the fingers and toes, constipation/diarrhea and some weakness. Clinical Trials There are a variety of options of therapy but due to the success of new drug development, new options of therapy are becoming more and more available for this condition. Since this process is evolving, some of these new options in treatment are only available to patients through clinical trials or research studies. These programs involve patient volunteers who help investigate different ways to treat diseases like cancer. Each study tries to answer specific scientific questions regarding different ways to prevent, diagnose and treat a disease. A patient should ask their doctor about the option of a clinical trial for them. Your physician will be able to run tests to determine if you are eligible to participate in a trial if one is available for you. It is important to know that many who participate in clinical trials are likely to receive state of the art treatment due to the stringent guidelines for delivery of care outlined in study protocols. If a trial is available to you, it is a great option and should be considered carefully by a patient to have as part of their treatment plan. Use of Bisphosphonates Bisphosphonates are medicines that appear to strengthen bones and can improve bone density. Bone defects and bone density losses are common in patients with multiple myeloma so use of these agents on a periodic basis can add in improvement of bone health. They are more effective when used with supplements of Vitamin D and calcium. Some evidence exists that use of these drugs may also prolong remission status through a variety of mechanisms and use of these agents alone may prolong survival of patients with this condition. Drugs approved for this purpose presently include Zolendronic acid (Zometa ) and Pamidronate (Aredia ). The role of bone deriving agents like Denosumab (Xgeva ) is currently uncertain in patients with multiple myeloma

8 Glossary Bone Marrow - this is an area located in the bone where early forms of blood cells are formed before being released into the circulation. Many types of blood cancers will be able to be diagnosed from a biopsy of this area. Electropheresis (Serum [SPEP] or Urine[UPEP]) - this is a test that measures the concentration of immunoglobulins based upon their size but also the electric field that these proteins generate leading to a pattern that can be read to determine the concentration and pattern of production by plasma cells. The type of electrophoresis is determined whether the analysis is carried out on blood (serum) or urine. Immunoglobulins - one class of structurally related proteins which consists of two pairs of polypeptide chains, one pair of light (L) and one pair of heavy (H) chains-these proteins are connected by a disulfide bonds. There are several types including IgGm IgA, IgM, IgD and IgE. These are forms of antibodies that are responsible for fighting off infection. Leukocytes - another term for white blood cells. Light Chains - proteins that are secreted by plasma cells, typically found in the urine. M-Protein - refers to the marker seen in the serum or urine on the SPEP/UPEP and is monitored to determine the concentration of protein produced from the malignant plasma cell. Plasma Cells - one of many types of white blood cells. Plasma cells form antibodies that help with fighting off infection. This is the cell that becomes malignant in multiple myeloma. Plasma Cell Labeling Index - this is a test that involves looking at a slide of bone marrow cells and determining the percentage of plasma cells in the S phase of the cell cycle. In many centers, it is still considered a research tool. Renal Function - related to the function of the kidneys. Red Blood Cells (erythrocytes) - types of blood cells that carry oxygen and contain hemoglobin. White Blood Cells - types of blood cells that help fight off infection

9 Contributions are Needed and Appreciated If you have found this information helpful, we would like you to consider giving a donation to the ACCC to help with continuance of the organization's mission to educate our public about aspects related to cancer. We provide materials like this daily to patients and their families, nurses and physicians in order to help with the explanation of what might come next after a diagnosis of cancer. Your kind gift will help continue this special mission of education. The ACCC feels strongly that education and information is empowering and provides hope for tomorrow for problems we face today. Contributions can be sent to the Alamo City Cancer Council, 100 NE Loop 410, Suite 600, San Antonio, TX or click the Make a Donation link at More Information on Multiple Myeloma American Society of Clinical Oncology (ASCO) patient website: The National Cancer Institute: trials The American Cancer Society: International Myeloma Foundation: Multiple Myeloma Research Foundation (MMRF): The Leukemia and Lymphoma Society:

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