Multiple Myeloma Cancer B-cell development memory stem & CLL germinal Bce" . mature center @ cell a naive B-cell ; B-cell - f lymphoid e-: progenitor “EBs om um \ progenitor-B ae / tN pre-B DLBCL, ) rate FL, HL — cel B-cell Bone marrow Lymplietd tissue DLBCL (Diffuse large B cell lymphoma) FL (Follicular lymphoma) HL (Hodgkin lymphoma)What is Multiple Myeloma? An estimated 1420, 180 people diagnosed in the World in 2010 , . f blood cancer in which plasma cells grow aye itrollably, usually inside the bone marrow hat cause structural + Associated with bone lesions t i damage and/or fractures from overproduction of myeloma cells * Referred to as multiple myeloma because about 90% of patients have multiple bone lesions * Solitary plasmacytoma: a mass of myeloma cells in one site in the bone or another organ * Extramedullary plasmacytoma: myeloma that begins in other tissues, such as skin, muscle or lungs What is the Function of Plasma Cells? * Found inside the bone marrow * Part of the body’s immune system that produce antibodies to help the body fight infectiony What are the Risk Factors for Multiple Myeloma? Age: Myeloma occurs most commonly in people over 60 years. The average age at diagnosis is 70 years. Only 2% of cases occur in people under 40 years. Race: Myeloma occurs twice as frequently in black people than in white people for unclear reasons. Exposure to radiation and chemicals History of solitary plasmacytoma Gender: more common in men Monoclonal gammopathy of unknown significance (MGUS, Paraproteinemia): is a condition in which an abnormal protein (monoclonal protein, paraprotein or M protein) is present in the blood at low level with no associated cause e.g. disease. What are the Symptoms of Multiple Myeloma? General Hypercalcemia ¢ Weight loss * Nausea and vomiting * Easy bruising * Increased urination * Hazy vision * Excessive thirst * Bleedinggums [| ‘ oN Bones s Pi ¢ Pain = & ¢ FracturesWhat are the Symptoms of Multiple Myeloma? cont... Kidney Failure Amyloidosis. (build-up of proteins) * Peripheral neuropathy (nerve damage) * Edema (swelling caused by build-up of fluid in the body) * Enlargement of organs + Nausea and vomiting ¢ Fatigue * Weakness What are the Symptoms of Multiple Myeloma? cont... Bone Marrow/Immune System Blood and Circulation * Anemia Disorders + Bleeding * Shortness of breath « Infections * Blood clots * Pneumonia * BleedingHow is Multiple Myeloma Diagnosed? + Blood test for anemia, kidney function, and calcium levels + Blood and urine tests to measure M protein levels * Diagnosis is confirmed with a bone marrow biopsy ° X-ray * Magnetic resonance imaging (MRI) * Computed tomography (CT or CAT) scan * Positron emission tomography (PET) scan or PET-CT Multiple Myeloma Staging * Durie-Salmon system (D-S) * The International Staging System (ISS)Durie-Salmon Staging System ‘N * Assesses the extent of the disease or size of the tumor * Divided into 3 stages + Each stage is classified into A or B depending on kidney function * Based on laboratory data including: — Red blood cell counts — Blood calcium levels — M protein levels — Amount of bone damage Durie-Salmon Staging System cont... * the symptoms related to the myeloma include hypercalcemia (elevated blood Calcium), poor Renal or kidney function, Anemia or Bone pain or bone lesions (CRAB). — Calcium levels increased: serum calcium > 0.25 mmol/L above the upper limit of normal or > 2.75 mmol/L — Renal insufficiency: creatinine > 173 mmol/L — Anemia: hemoglobin 2.g/dL below the lower limit of normal or hemoglobin < 10g/dL — Bone lesions; lytic lesions or osteoporosis (thinning of the bones) with compression fractures (an MRI or CT test may clarify) * Other: blood hyperviscosity, amyloidosis and/or recurren bacterial infections (more than 2 episodes in 12 months)y D-S Stage | Myeloma * Few cancer cells present in the body * May have no symptoms * Normal or slightly below normal red blood cell count * Normal calcium levels * Very low levels of M protein in the blood or urine * No bone damage on x-rays D-S Stage II Myeloma * More cancer cells are present in the body + Criteria for stage Il are defined as those that fit neither stage | nor stage Ill myelomaD-S Stage III Myeloma * Large number of cancer cells are present in the body * Anemia with a hemoglobin level less than 8.5 gm/dL Elevated blood calcium levels Advanced bone damage (more than three bone lesions) ° High levels of M protein in the blood or urine International Staging System (ISS) * Defines the factors that influence a person’s survival * Also divided into 3 stages * Based on laboratory data including: — Serum albumin — Serum betay-microglobulin (B2-M), a protein presents on all nucleated cells and plays a role in immunologic defense. B2-M may indicate a large number of myeloma cells are present and kidney damage has occurred.ISS , cont... + ISS Stage |: — B2-M levels are less than 3.5 gm/dL (grams per deciliter) — Blood albumin levels are greater than or equal to 3.5 gm/db * SS Stage Il: — Criteria for stage II are defined as those that fit neither stage | nor stage Ill myeloma « ISS Stage III: — B2-M level greater than 5.5gm/db How is Multiple Myeloma Treated? ¢ Treatment depends on many factors ¢ More than one treatment may be used * Active Surveillance (watchful wait): close observation without treatment for patients with no symptoms * Chemotherapy * Radiation therapy ¢ Surgery * Stem cell transplantationCancer Treatment: Chemotherapy ‘N A combination of medications is often used i * Typical medications include cyclophosphamide (Cytoxan, Neosar), doxorubicin (Adriamycin), Doxorubicin liposome injection (Doxil), melphalan (Alkeran), vincristine (Oncovin), etoposide (Toposar, VePesid), cisplatin (Platinol), carmustine (BCNU) and dexamethasone (Decadron). Newer drugs include: thalidomide (Thalomid), lenalidomide (Revlimid), and bortezomib (Velcade; proteasome inhibitor) Side effects may include fatigue, risk of infection, nausea and vomiting, loss of appetite, and diarrhea Cancer Treatment: Radiation Therapy ¢ External beam: outside the body * May be used to control pain when chemotherapy is not effective * Not used to control bone pain due to structural damage + Side effects may include fatigue, mild skin reactions, upset stomach, and loose bowe\ movementsCancer Treatment: Surgery + Not used to treat myeloma * May be used to relieve pressure froma plasmacytoma * Kyphoplasty (Vertebroplasty): inflating and injecting bone cement into vertebrae to relieve pain, restore lost height and strengthen the spine Cancer Treatment: Stem Cell Transplantation/Bone Marrow Transplantation ¢ High-dose chemotherapy used to kill cancer cells « New stem cells are introduced from the patient (autologous) or a donor (allogeneic) to form new blood cells + Autologous stem cell transplantation is considered the standard treatment * Allogeneic stem cell transplantation is only recommended for patients with high-risk or recurrent myelomaSupportive Therapy for Myeloma ~ \ « Used to reduce symptoms and complications from myeloma * Treatment of anemia * Antibiotics and rarely intravenous immunoglobulins to treat and prevent infection * Bisphosphonate medications (drugs that increase bone density) to alleviate bone pain, reduce the risk of fractures and prevent hypercalcemia * Balanced diet high in calories, protein and healthy fluids * Exercise to maintain bone strength and reduce calcium loss After Treatment * Patients should talk with the physician about developing a follow-up care plan * Physician may recommend regular physical examinations, imaging tests and blood tests * Maintenance therapy for a year or longer to prevent recurrence * Intravenous bisphosphonates monthly * Fear of recurrence is common; patients should talk with your physician about ways to cope