• 93% of patients will have more than one pathological fracture and/or bone lesion.
• 70% of patients will have bone pain.
• Bleeding can occur because of thrombocytopenia and even more rarely from monoclonal protein which impacts clotting.
• As many as 30% of patients with multiple myeloma will present with hypercalcemia which can cause bone pain, nausea, thirst, and constipation.
• If the patient is presenting symptoms of weakness, back pain, numbness, or dysesthesias in their extremities a spinal cord compression should be considered.
• Severe cases of anemia can be present.
• Infections such as shingles, Pneumococcal organisms, and Haemophilus are common due to leukopenia and abnormal humoral immunity.
• Patients with a high tumor volume may present with epistaxis.
• Generalized malaise, fever, sluggish mentation, paresthesia, sensory loss, and infection can indicate hyperviscosity.
• Meningitis and carpal tunnel syndrome are both common neurologic symptoms associated with myeloma.

• Pain

  This includes comfort measures, pain control, and interventions that maintain function. Supportive care includes managing the bone disease, anemia, infections, kidney failure, and pain associated with multiple myeloma. [orthoinfo.aaos.org]

  Interventional radiology Interventional radiology may be used to relieve pain during treatment. Radiation therapy Radiation therapy for multiple myeloma is used when plasma cells have grown into the bone marrow and caused bone damage and pain. [cancercenter.com]

  Throughout the summer and fall, I’d also been experiencing rib pain, and I suffered a sharp back pain while helping a friend move furniture. [mdanderson.org]

• Anemia

  The patient in our case study suffered refractory anemia following surgery and 2 cycles of chemotherapy. Initially, the anemia was considered to be a common manifestation of CRC in this patient. [ncbi.nlm.nih.gov]

  This interferes with blood cell production leading to anemia, leukopenia, and thrombocytopenia. High levels of infection are common which can lead to the overproduction of certain antibodies. [symptoma.com]

  Erythropoietin or occasional blood transfusions can manage anemia. Antibody infusions and vaccinations can help patients with recurrent infections. [orthoinfo.aaos.org]

• Amyloidosis

  […] therapy in AL amyloidosis. [hematologyandoncology.net]

  In general, the presentation of hepatic amyloidosis varies with minimal or no symptoms commonly seen. Hepatic amyloidosis is rarely associated with multiple myeloma. [ncbi.nlm.nih.gov]

• Fatigue

  Fatigue When the disease progresses, symptoms may include: Fatigue Weakness Broken bones Repeat infections Nausea and vomiting Constipation Difficulty urinating Abnormal bleeding Headache Visual problems Confusion Diagnosis Your doctor may need pictures [cancer.uvahealth.com]

  Patients who have high levels of calcium in their blood may experience nausea, fatigue, confusion, constipation, and frequent urination. Patients with anemia may experience fatigue, weakness, and shortness of breath with exercise. [orthoinfo.aaos.org]

  She developed G2 AEs, including nausea and fatigue. The cardiac amyloidosis worsened, and she died of heart and renal failure. Case 3: The patient was a 79-year-old male with BJP-κ. [ncbi.nlm.nih.gov]

  This may result in anemia (low red blood cell count), which often causes shortness of breath, fatigue or a feeling of weakness; leukopenia (low white blood cell count), which may increase the risk of infections; or thrombocytopenia (low blood platelet [cancercenter.com]

• Weakness

  These events lead to bone pain, kidney damage, and a weak immune system. [cancer.uvahealth.com]

  Patients with anemia may experience fatigue, weakness, and shortness of breath with exercise. In advanced cases, patients typically have recurrent infections and can have kidney failure. [orthoinfo.aaos.org]

  Multiple myeloma cells can eat away at areas of bone, making them weak. [cancer.osu.edu]

  Hypercalcemia: A buildup of calcium in the blood can cause kidney damage, fatigue, muscle weakness, loss of appetite, nausea, and confusion. Anemia: A lack of growth of red blood cells causes extreme tiredness, weakness, and dizziness. [uihc.org]

• Easy Bruising

  Easy bruising or bleeding. Trouble breathing. Weakness of the arms or legs. Feeling very tired. A tumor can damage the bone and cause hypercalcemia (too much calcium in the blood). [rogelcancercenter.org]

  When they do occur, symptoms include: Bone pain, particularly in the back and ribs Easily broken bones (fractures) Tiredness, lethargy or shortness of breath on exertion – usually caused by too few red blood cells in the body (anaemia) Easy bruising or [betterhealth.vic.gov.au]

  bruising) A compromised immune system (resulting in various types of infections) Myeloma kidney (monoclonal antibodies collect in the kidneys, which can interfere with kidney function) Kidney stones (from an increase in uric acid caused by the growth [verywellhealth.com]

  Decreased platelet production impairs the blood's ability to clot and results in easy bruising or bleeding. [merckmanuals.com]

• Pneumonia

  We report the case of a 25-year-old man with femoral Streptococcus pneumoniae pyomyositis as well as hypercalcemia, mild anemia, and elevated inflammatory markers; he subsequently was diagnosed with immunoglobulin G (IgG) kappa multiple myeloma. [ncbi.nlm.nih.gov]

  The most common side effects for isatuximab included neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia. [medscape.com]

  Pneumonia is a common and serious infection. Videos About Multiple Myeloma [myelomacrowd.org]

• Dyspnea

  Care Delivery Interventions for Dyspnea A review of supportive cancer services identified many studies, but only 6 measured dyspnea. [doi.org]

  Dyspnea Dyspnea was reported in patients treated with Kyprolis. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop Kyprolis for Grade 3 or 4 dyspnea until resolved or returned to baseline. [investors.amgen.com]

  The dyspnea had progressed to the point that she could only walk one block without stopping. [archbronconeumol.org]

  Cardiopulmonary symptoms such as shortness of breath, exertional dyspnea, orthopnea, and dependent edema should raise concern for secondary AL amyloidosis or light chain deposition disease with cardiac involvement. [cancertherapyadvisor.com]

• Visual Hallucination

  Some patients present with transient confusion or episodes of visual misperceptions. [emedicine.medscape.com]

• Kidney Failure

  Supportive care includes managing the bone disease, anemia, infections, kidney failure, and pain associated with multiple myeloma. Bisphosphonate medications can prevent destructive bone lesions and spine fractures. [orthoinfo.aaos.org]

  Unlike a diagnosis of breast cancer, colon cancer, or lung cancer, the diagnosis of multiple myeloma is based on your doctor identifying that mutated plasma cells are causing fractures, anemia, and/or kidney failure. [hematology.org]

  However, it can clog up your kidneys and give you kidney failure. [msdmanuals.com]

  Regarding the presence of back pain, anemia, hypercalcemia, and kidney failure, a diagnosis of MM was suspected. A skeletal survey showed punched-out lesions in the skull. [ncbi.nlm.nih.gov]

• Polyuria

  Symptomatic hypercalcaemia may present in a dramatic fashion with confusion, disorientation, muscle weakness, constipation, anorexia, polyuria and polydipsia. [racgp.org.au]

  Hypercalcemia may cause polyuria and polydipsia, muscle cramps, constipation, and a change in the patient’s mental status. Dimopoulos M, Kyle R, Fermand JP, Rajkumar SV, San Miguel J, et al. [emedicine.medscape.com]

• Oliguria

  […] patients with myeloma, and is typically due to light chain deposition within the distal and collecting renal tubules or hypercalcaemia.4 It is most commonly detected as an asymptomatic elevation in serum creatinine, but patients may rarely present with oliguria [racgp.org.au]

• Confusion

  She became acutely confused with a Glasgow Coma Scale score of 10/15 and a CT head showed no acute pathology. Further investigation with a lumbar puncture confirmed the diagnosis of streptococcal meningitis. [ncbi.nlm.nih.gov]

  Fatigue When the disease progresses, symptoms may include: Fatigue Weakness Broken bones Repeat infections Nausea and vomiting Constipation Difficulty urinating Abnormal bleeding Headache Visual problems Confusion Diagnosis Your doctor may need pictures [cancer.uvahealth.com]

  Hypercalcemia: A buildup of calcium in the blood can cause kidney damage, fatigue, muscle weakness, loss of appetite, nausea, and confusion. Anemia: A lack of growth of red blood cells causes extreme tiredness, weakness, and dizziness. [uihc.org]

  […] calcium in the blood can affect many parts of the body, including the kidneys, nerves, heart, muscles and digestive tract, leading to: Loss of appetite Nausea or vomiting Feeling thirsty Frequent urination Constipation Feeling very tired Muscle weakness Confusion [cancer.osu.edu]

• Peripheral Neuropathy

  The mechanism of the development of the peripheral neuropathy is poorly understood. [ncbi.nlm.nih.gov]

• Dizziness

  One patient experienced dose limiting toxicity of dizziness and diarrhea. The most frequent non-hematologic toxicity was infection (79%). Serious adverse events included cord compression and sepsis. [ncbi.nlm.nih.gov]

  Hypercalcemia, caused by high levels of calcium in the blood, may cause excessive thirst, frequent urination, nausea, dehydration and constipation, as well as mental confusion, dizziness or even coma. [cancercenter.com]

  Get medical help right away if you get any of the following symptoms: shortness of breath or trouble breathing dizziness or lightheadedness (hypotension) cough wheezing throat tightness runny or stuffy nose headache itching nausea vomiting chills fever [darzalex.com]

  Anemia: A lack of growth of red blood cells causes extreme tiredness, weakness, and dizziness. [uihc.org]

  Common symptoms include: Anaemia, tiredness, fatigue, weakness and dizziness Increased bleeding or bruising Bone pain Elevated blood calcium level Frequent or repeated infections Causes The exact cause of myeloma remains unknown. [leukaemia.org.nz]

• Headache

  PATIENT CONCERNS AND DIAGNOSES: Herein, we describe an extraordinary rare case of multiple myeloma with initial presentation of a left sphenoid neoplasm resulting in left-sided headache and rapid deterioration of visual acuity. [ncbi.nlm.nih.gov]

  Fatigue When the disease progresses, symptoms may include: Fatigue Weakness Broken bones Repeat infections Nausea and vomiting Constipation Difficulty urinating Abnormal bleeding Headache Visual problems Confusion Diagnosis Your doctor may need pictures [cancer.uvahealth.com]

  […] shortness of breath – caused by anaemia high levels of calcium in the blood (hypercalcaemia) – which may cause symptoms including extreme thirst, stomach pain, needing to pee frequently, constipation or confusion weight loss blurred vision, dizziness or headaches [nhs.uk]

  Get medical help right away if you get any of the following symptoms: shortness of breath or trouble breathing dizziness or lightheadedness (hypotension) cough wheezing throat tightness runny or stuffy nose headache itching nausea vomiting chills fever [darzalex.com]

• Stroke

  A literature review provided 84 reports from the license holder, 2 more cases of stroke in patients with MM receiving lenalidomide and a recurrent stroke in a patient experiencing polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and [ncbi.nlm.nih.gov]

  Howard S Kirshner, MD Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine; Director, Vanderbilt Stroke Center; Program Director, Stroke Service, Vanderbilt [emedicine.medscape.com]

  This stops the blood clogging small blood vessels, which can cause confusion, dizziness and stroke-like symptoms. [betterhealth.vic.gov.au]

  Other symptoms can include stroke, gastrointestinal disorders, enlarged liver, diminished spleen function, diminished function of the adrenal and other endocrine glands, skin color change or growths, lung problems, bleeding and bruising problems, fatigue [en.wikipedia.org]

  Before taking Tadora (Tadalafil), tell your doctor if you have or have had: Heart problems such as angina, heart failure or irregular heartbeat or have had a heart attack Low blood pressure or high blood pressure that is not controlled A stroke Liver [generic4all.name]

• Constipation

  Hypercalcemia, caused by high levels of calcium in the blood, may cause excessive thirst, frequent urination, nausea, dehydration and constipation, as well as mental confusion, dizziness or even coma. [cancercenter.com]

  The patient got severe constipation with difficulty in the passage of both gas and feces for 7 days. The patient was diagnosed with a small intestinal obstruction initially and then developed type II respiratory failure. [ncbi.nlm.nih.gov]

  Fatigue When the disease progresses, symptoms may include: Fatigue Weakness Broken bones Repeat infections Nausea and vomiting Constipation Difficulty urinating Abnormal bleeding Headache Visual problems Confusion Diagnosis Your doctor may need pictures [cancer.uvahealth.com]

  Too much calcium in the blood can affect many parts of the body, including the kidneys, nerves, heart, muscles and digestive tract, leading to: Loss of appetite Nausea or vomiting Feeling thirsty Frequent urination Constipation Feeling very tired Muscle [cancer.osu.edu]

• Nausea

  She developed G2 AEs, including nausea and fatigue. The cardiac amyloidosis worsened, and she died of heart and renal failure. Case 3: The patient was a 79-year-old male with BJP-κ. [ncbi.nlm.nih.gov]

  Hypercalcemia, caused by high levels of calcium in the blood, may cause excessive thirst, frequent urination, nausea, dehydration and constipation, as well as mental confusion, dizziness or even coma. [cancercenter.com]

  Nausea and vomiting may occur as a result of myeloma treatment, and bland foods can reduce the risk. Include protein-rich foods in the diet, such as eggs, fish, or nuts. Eat whole-grain foods, such as whole wheat bread and rice. [medicalnewstoday.com]

• Diarrhea

  For this reason we report this rare case in which diarrhea and abdominal pain were the initial presenting symptoms of multiple myeloma with a plasmacytoma. [ncbi.nlm.nih.gov]

  The most common side effects for isatuximab included neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia. [medscape.com]

• Polydipsia

  Symptomatic hypercalcaemia may present in a dramatic fashion with confusion, disorientation, muscle weakness, constipation, anorexia, polyuria and polydipsia. [racgp.org.au]

  Peripheral neuropathy, carpal tunnel syndrome (especially with associated amyloid disease), abnormal bleeding, and symptoms of hypercalcemia (eg, polydipsia, dehydration) are common. Patients may also present with renal failure. [msdmanuals.com]

  Hypercalcemia may cause polyuria and polydipsia, muscle cramps, constipation, and a change in the patient’s mental status. Dimopoulos M, Kyle R, Fermand JP, Rajkumar SV, San Miguel J, et al. [emedicine.medscape.com]

• Macroglossia

  The aim of this report is to describe a clinical case of an elderly patient with dysphagia related to macroglossia and enlargement caused by primary amyloidosis associated with multiple myeloma. [ncbi.nlm.nih.gov]

  Carpal tunnel syndrome is quite common but only rarely caused by AL amyloidosis Macroglossia: marked enlargement of the tongue because of amyloid deposits Not everyone will have all or any of these symptoms and complications. [myeloma.org.uk]

  The following is a list of symptoms and signs of multiple myeloma: Anemia Bleeding Nerve damage Skin lesions (rash) Enlarged tongue (macroglossia) Bone tenderness or pain, including back pain Weakness, fatigue or tiredness Infections Pathologic bone fractures [medicinenet.com]

  Macroglossia may occur secondary to amyloid deposition in the tongue and is a common finding in patients with amyloidosis (see the image below). Amyloidosis infiltrating the tongue in multiple myeloma. [emedicine.medscape.com]

• Bleeding Gums

  – such as frequent nosebleeds, bleeding gums and heavy periods Myeloma doesn't usually cause a lump or tumour. [nhs.uk]

  However, if you have these symptoms, you should call your doctor right away: Fever Bleeding (such as nosebleeds, bleeding gums or severe bruising) Skin rash Cough that doesn’t go away These are some of the more serious side effects of melphalan. [familydoctor.org]

  gums, or other unusual bleeding Kidney damage and spinal cord compression may also occur, potentially leading to numbness, weakness, and tingling in the legs. [medicalnewstoday.com]

• Cardiomegaly

  Cardiovascular system examination may reveal cardiomegaly secondary to immunoglobulin deposition. Amyloidosis may develop in some patients with MM. [emedicine.medscape.com]

  […] assessment: Sensory level change (ie, loss of sensation below a dermatome corresponding to a spinal cord compression), neuropathy, myopathy, positive Tinel sign, or positive Phalen sign Abdominal examination: Hepatosplenomegaly Cardiovascular evaluation: Cardiomegaly [emedicine.com]

• Retinal Hemorrhage

  Sludging in the capillaries resulting in purpura, papilledema, central nervous system symptoms, retinal hemorrhage, or coronary ischemia can occur. [symptoma.com]

  Purpura, retinal hemorrhage, papilledema, coronary ischemia, seizures, and confusion may occur as a result of hyperviscosity syndrome. [emedicine.medscape.com]

  Sludging in the capillaries can result in purpura, retinal hemorrhage, papilledema, coronary ischemia, or central nervous system (CNS) symptoms (eg, confusion, vertigo, seizure). [emedicine.com]

• Cotton Wool Spots

  Physical Examination On head, ears, eyes, nose, and throat (HEENT) examination, the eyes may show exudative macular detachment, retinal hemorrhage, or cotton-wool spots. Pallor from anemia may be present. [emedicine.medscape.com]

  Examination for MM may reveal the following: HEENT examination: Exudative macular detachment, retinal hemorrhage, or cotton-wool spots Dermatologic evaluation: Pallor from anemia, ecchymoses or purpura from thrombocytopenia; extramedullary plasmacytomas [emedicine.com]

• Purpura

  Two patients (33.3%) experienced AE (also considered adverse drug reactions) leading to study discontinuation: thrombotic microangiopathy (Day 11/Cycle 1) and thrombotic thrombocytopenic purpura (Day 6/Cycle 2). [ncbi.nlm.nih.gov]

  The most common symptoms are joint pain (arthralgia), pain and numbness in the fingers and toes in response to cold (Raynaud’s phenomenon), weakness, and purpura. [rarediseases.org]

  Post-proctoscopic peripalpebral purpura strongly suggests amyloidosis. [emedicine.medscape.com]

  Sludging in the capillaries resulting in purpura, papilledema, central nervous system symptoms, retinal hemorrhage, or coronary ischemia can occur. [symptoma.com]

  Thrombotic Thrombocytopenic Purpura /Hemolytic Uremic Syndrome (TTP/HUS) Cases of TTP/HUS including fatal outcome have occurred in patients receiving Kyprolis. Monitor for signs and symptoms of TTP/HUS. [investors.amgen.com]

• Night Sweats

  Other symptoms include: Fatigue Feeling ill Fever Night sweats Weight loss is not common in the early stages. Physically, patients are pale with diffuse bone tenderness, especially around the sternum (breastbone) and pelvis (hips). [orthoinfo.aaos.org]

  Key symptoms include: Fatigue and generalized weakness Musculoskeletal symptoms, especially bone pain Unintentional weight loss Night sweats Recurrent infections, especially upper respiratory infections Paresthesias Key signs may include: Conjunctival [cancertherapyadvisor.com]

• Pruritus

  Her pruritus resolved, but the lesions persisted. Footnotes Competing interests: None declared. This article has been peer reviewed. [cmaj.ca]

• Bone Pain

  […] fractures, bone pain, hypercalcemia, and anemia. [icd9data.com]

  The clinical features are bone pain, renal impairment, immunodeficiency, anemia and presence of abnormal immunoglobulins (Ig). [orpha.net]

  As the plasma cell tumor grows, it also destroys the bone around it. These events lead to bone pain, kidney damage, and a weak immune system. [cancer.uvahealth.com]

  Infrequently, these tumors develop in areas other than bone, particularly in the lungs, liver, and kidneys. Because plasma cell tumors often invade bone, bone pain, often in the back, ribs, and hips, may occur. [merckmanuals.com]

  Additionally, the myeloma cells commonly produce substances that cause bone destruction, leading to bone pain and/or fractures. Myeloma cells are produced in the bone marrow, the soft tissue inside your bones. [hematology.org]

• Osteoporosis

  Woitge HW, Horn E, Keck AV, Auler B, Seibel MJ, Pecherstorfer M: Biochemical markers of bone formation in patients with plasma cell dyscrasias and benign osteoporosis. Clin Chem 2001;47:686–693. [doi.org]

  He later developed hematuria, proteinuria, multiple osteoporosis in the costal bones, and thrombocytopenia. These new symptoms drew our attention, and we considered a diagnosis of synchronous primary CRC and MM, with the anemia as a symptom of MM. [ncbi.nlm.nih.gov]

  A person with SMM may be prescribed bisphosphonates for symptoms of osteoporosis or osteopenia and/or a new therapy being studied in a clinical trial. Osteopenia is a condition in which a person has a low density of bone minerals. [cancer.net]

  Diffuse osteoporosis or discrete osteolytic lesions develop, usually in the pelvis, spine, ribs, femur, humerus, and skull. [msdmanuals.com]

• Back Pain

  She was admitted with a complaint of low back pain. Regarding the presence of back pain, anemia, hypercalcemia, and kidney failure, a diagnosis of MM was suspected. A skeletal survey showed punched-out lesions in the skull. [ncbi.nlm.nih.gov]

  Throughout the summer and fall, I’d also been experiencing rib pain, and I suffered a sharp back pain while helping a friend move furniture. [mdanderson.org]

• Myopathy

  Early radiologic identification of polyarticular amyloid arthropathy and myopathy should prompt confirmatory biopsy to confirm the diagnosis. [ncbi.nlm.nih.gov]

  Neurologic findings may include a sensory level change (ie, loss of sensation below a dermatome corresponding to a spinal cord compression), neuropathy, myopathy, a Tinel sign, or a Phalen sign due to carpel tunnel compression secondary to amyloid deposition [emedicine.medscape.com]

  prostatic, retroperitoneal areas) Musculoskeletal examination: Bony tenderness or pain without tenderness Neurologic assessment: Sensory level change (ie, loss of sensation below a dermatome corresponding to a spinal cord compression), neuropathy, myopathy [emedicine.com]

• Tinel's Sign

  Neurologic findings may include a sensory level change (ie, loss of sensation below a dermatome corresponding to a spinal cord compression), neuropathy, myopathy, a Tinel sign, or a Phalen sign due to carpel tunnel compression secondary to amyloid deposition [emedicine.medscape.com]

  sign, or positive Phalen sign Abdominal examination: Hepatosplenomegaly Cardiovascular evaluation: Cardiomegaly In patients with MM and amyloidosis, the characteristic examination findings include the following: Shoulder pad sign Macroglossia Typical [emedicine.com]

• Epistaxis

  Patients with a high tumor volume may present with epistaxis. Generalized malaise, fever, sluggish mentation, paresthesia, sensory loss, and infection can indicate hyperviscosity. [symptoma.com]

  Serum viscosity: should be assessed if there is epistaxis, and when there are neurological symptoms or very high paraprotein levels. [patient.info]

  Not recognizing Tumor Lysis Syndrome (although rare, this can result in significant morbidity) Not recognizing Hyperviscocity Syndrome (may present as bleeding, particularly epistaxis, neurologic complaints [i.e., headache, blurred vision, tinnitus, delirium [clinicaladvisor.com]

  Rarely, affected individuals may experience repeated nosebleeds (epistaxis). [rarediseases.org]

The standard workup for patients who are suspected of having multiple myeloma includes many components. The 2009 International Workshop created guidelines to standardize the investigative workup:

• Bone marrow biopsy and/or bone marrow aspiration
• Skeletal survey
• Standard metaphase cytogenetics
• MRI’s
• Fluorescent in situ hybridization
• Urine and serum assessment for monoclonal protein
• Serum-free light chain assay
• Serum beta (2)-microglobulin, lactate dehydrogenase, and albumin measurement
• Complete blood count looking for thrombocytopenia, anemia, leukopenia
• A complete metabolic panel of protein, albumin and globulin, creatinine, uric acid, and blood urea nitrogen levels.
• A 24-hour urine collection to quantify creatinine and Bence Jones protein clearance

Imaging

PET scans and whole body MRI’s can be used to evaluate the extent of the multiple myeloma. Using both scanning techniques is thought to be helpful in assessing the effectiveness of expensive and aggressive treatments. Currently, however, PET scans are not part of standard practices. Bone scans should not be used in evaluating multiple myeloma as more than 50% of lesions tend to be missed.

Others

Bone marrow biopsies and aspirations can be used to evaluate the extent of malignancy. Using both allows the doctor to calculate the percentage of plasma cells in the aspirate, though the biopsy tends to be more accurate.

Staging

There are currently two staging systems in use to determine the severity of multiple myeloma in patients. The Salmon-Durie System has been in use since 1975 and the International Staging System was developed in 2005 [4] [5] [6].

Salmon-Durie Staging System

Stage 1:

• Cell mass is less than 0.6 × 1012 cells/m2
• Serum calcium value less than 12 mg/dL
• Hemoglobin value greater than 10 g/dL
• Only one bone plasmatoma on radiographs or a normal bone structure with a scale of 0
• Urine light-chain M component on electrophoresis less than 4 g/24 h
• IgG value less than 5 g/dL
• IgA value less than 3 g/dL

Stage 2:

• Cell mass is 0.6-1.2 × 1012 cells/m2
• Does not meet the criteria for stage 1 or stage 3

Stage 3:

• Cell mass is greater than 1.2 × 1012 cells/m2
• Serum calcium value greater than 12 mg/dL
• Advanced lytic bone lesions (scale 3) on radiographs
• Hemoglobin value equal to 8.5 g/dL
• IgG value greater than 7 g/dL
• IgA value greater than 5 g/dL
• Urine light-chain M component on electrophoresis greater than 12 g/24 h

International Staging System

Stage 1:

• CRP ≥4.0 mg/dL
• Beta-2 microglobulin less than or equal to 3.5 g/dL and albumin ≥3.5 g/dL
• Absence of chromosome 13 deletion
• Low serum IL-6 receptor
• Plasma cell labeling index < 1%
• Long duration of initial plateau phase

Stage 2:

• Beta-2 microglobulin level ≥3.5 to < 5.5 g/dL, or
• Beta-2 microglobulin < 3.5 g/dL and albumin < 3.5 g/dL

Stage 3:

• Beta-2 microglobulin of 5.5 g/dL or more

• Multiple Lytic Bone Lesions

  An increased incidence of multiple lytic bone lesions ( P < .001) was observed in LCO patients compared with IgG and IgA patients but was not apparent in bone pain or fractures ( Table 2 ). Table 2. [doi.org]

• Hyperviscosity

  Hyperviscosity: Emergent plasmapheresis B. [clinicaladvisor.com]

  General processes Hyperviscosity syndrome can occur with immunoglobulin A, immunoglobulin G3, and immunoglobulin G1. [symptoma.com]

  * 요약 : IgM, no osteolytic lesion * WM-related symptoms : anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly 끝. 2018. 10. 13 - SJH [sondoctor.co.kr]

  Hyperviscosity is managed through plasmapheresis and prompt initiation of chemotherapy targeting the MM-clone. [cancertherapyadvisor.com]

  The three most common disorders that may occur in association with multiple myeloma include hyperviscosity syndrome, cryoglobulinemia, or amyloidosis. [rarediseases.org]

• Neutropenia

  Sarclisa can also cause neutropenia and health care professionals should monitor a patient’s complete blood cell count periodically during treatment, as well as monitor patients with neutropenia for signs of infection. [fda.gov]

  Patients in the lenalidomide group had a higher incidence of grade 3 neutropenia (25.0%) than did those in the placebo group (2.3%). [content.nejm.org]

  Treatment with MAbs in combination with bortezomib or lenalidomide plus dexamethasone resulted in longer PFS (HR 0.83, 95% CI: 0.66-0.98), fewer incidences of at least grade 3 thrombocytopenia (RR 0.35, 95% CI: 0.23-0.53), neutropenia (RR 0.70, 95% CI [ncbi.nlm.nih.gov]

  The most common side effects for isatuximab included neutropenia, infusion-related reactions, pneumonia, upper respiratory tract infection, diarrhea, anemia, lymphopenia, and thrombocytopenia. [medscape.com]

  If patients are or are likely to develop neutropenia, consider antibiotic prophylaxis with a fluoroquinolone or penicillin-based antibiotic such as amoxicillin-clavulanate. [clinicaladvisor.com]

• Hyperuricemia

  In addition, factors that worsen renal function (eg, hypercalcemia, hyperuricemia, use of nephrotoxic drugs) should be avoided or treated. Several measures are often recommended but are of unproved efficacy. [msdmanuals.com]

  Diagnoses of hyperuricemia, hypercalcemic nephropathy, glomerulosclerosis, and light-chain nephropathy are also possible. Skeletal processes Wide spread skeletal destruction is caused by a rapid increase in plasma cells. [symptoma.com]

  Bence Jones proteins, immunoglobulins, albumin and Tamm-Horsfall proteins most common cause of renal failure in multiple myeloma direct nephrotoxicity of Bence Jones proteins on the epithelial cells of the renal tubules hypercalcemia and dehydration hyperuricemia [radiopaedia.org]

• Hypoalbuminemia

  CASE PRESENTATION: A 75-year-old man presented with progressive leg edema, had nephrotic range proteinuria, hypoalbuminemia, moderate renal failure, and occult blood in his urine. [ncbi.nlm.nih.gov]

  […] when the use of a pacemaker is advisable in patients with amyloidosis, the general recommendations must be followed; however, the threshold for implanting these devices is usually very low, given that other coexisting factors (autonomic neuropathy and hypoalbuminemia [cjasn.asnjournals.org]

  Bologa RM, Levine DM, Parker TS, et al: Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients. Am J Kidney Dis 32: : 107, 1998 -114, Crossref, Medline, Google Scholar 41. [jco.ascopubs.org]

  Bologa RM, Levine DM, Parker TS, et al: Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients. Am J Kidney Dis 32 : 107 -114, 1998 [Medline] 41. [web.archive.org]

• Normocytic Anemia

  Symptoms and Signs Symptoms and signs are predominantly those of the myeloma (eg, skeletal pain, pathologic fractures, diffuse osteoporosis, bacterial infections, hypercalcemia, normochromic-normocytic anemia out of proportion to the degree of renal failure [msdmanuals.com]

  […] myeloma). 18 The CRAB criteria have been slightly revised in the 2010 version and they include hypercalcemia with calcium level > 11.5 mg/dL, renal insufficiency with serum creatinine > 2.0 mg/dL or estimated creatinine clearance < 40 mL/min, normochromic normocytic [doi.org]

• Leukocytosis

  Also, reflecting this aggressive clinical presentation, a higher proportion of patients with pPCL have significant leukocytosis, elevated lactate dehydrogenase (LDH) and β2-microglobulin serum levels. [doi.org]

The main options for therapy include:

• Chemotherapy and immunosuppression (melphalan, cyclophosphamide, doxorubicin, thalidomide, lenalidomide, bortezomib, carfilzomib, pomalidomide, prednisone and dexamethasone)
• Autologous stem cell transplantation
• Radiation
• Surgical care

Prognosis of multiple myeloma is determined by 2 factors - how many tumors there are and how fast they are spreading. C-reactive protein and beta-2 microglobulin are both used to predict survival.

The median survival rates are as follows:

• 54 months if both proteins are less than 6 mg/L
• 27 months when only one protein is less than 6 mg/L
• 6 months when both proteins are more than 6mg/L

Factors that led to a poor prognosis are hypercalcemia, renal impairment, tumor mass, and Bence Jones proteinemia. Patients that undergo conventional therapy have an average survival rate of 3 years. Fifty percent of patients who undergo high-dose chemotherapy with stem-cell transplantation survive for longer than 5 years [3]. The leading cause of death for patients with a myeloma is a bacterial infection.

To date an exact cause for multiple myeloma has not been identified, but various factors have been suggested [1] [2]. Since most individuals diagnosed with the disorder are in the older age group the common thought is that decreased immune system that comes with age increases the chance of developing multiple myeloma. While no evidence suggests that the disease is hereditary, it has been reported in 2 or more first degree relatives and in identical twins. Oncogenes such as c-myc have been associated with plasma cell tumors early in their development.

Individuals working with toxic chemicals such as insecticides, herbicides, heavy metals, petroleum products, and asbestos could be at an increased risk for developing multiple myeloma though the risk cannot be quantified. A correlation between multiple myeloma and radiation has been identified in examining the medical histories of Nagasaki WWII survivors, who were exposed to more than 50 Gy of radiation. Of the 109,000 survivors, 29 died of a multiple myeloma between 1950 and 1976. While a link between pre-existing inflammatory diseases and multiple myeloma has been suggested, no case-control studies have been able to support the relationship.

Annually, approximately 4 in 100,000 people are diagnosed with multiple myeloma. The condition is twice as common in African Americans, followed by Caucasians and half as common with Asian Americans. The predominant age of diagnosis is between 40 and 80 years old. The median age of diagnosis for men is 69 and for women is 71. Men are one and a half times more likely to be diagnosed with multiple myeloma than women. The malignancy is one of African American’s top 10 causes of cancer deaths.

Multiple myeloma is characterized by the rapid growth of abnormal plasma cells in more than 10% of the patient’s bone marrow. Research suggests that the bone marrow microenvironment impacts the manner in which myelomas develop tumor cells. The cells that most often become malignant in multiple myelomas are the most mature of the B-lymphocytes. This occurs when the DNA sequence is rearranged when encoding into the structure of mature immunoglobulins. During the encoding immunoglobulin A, monoclonal immunoglobulin G, and/or light chains are overproduced. This overproduction is identified through the use of urine protein electrophoresis, or serum protein electrophoresis. Multiple myelomas are often the consequence of injuries or diseases in hematologic, renal, skeletal, and nervous systems as well as general processes.

General processes

Hyperviscosity syndrome can occur with immunoglobulin A, immunoglobulin G3, and immunoglobulin G1. Sludging in the capillaries resulting in purpura, papilledema, central nervous system symptoms, retinal hemorrhage, or coronary ischemia can occur.

Hematologic processes

Neutropenia, thrombocytopenia, and anemia result from plasma cells infiltrating bone marrow which can impact clotting factors leading to defects in how it interacts with other systems.

Renal processes

Renal processes linked to multiple myeloma, are most commonly amyloidosis, direct tubular injury, or mechanisms involved in plasmacytoma. Diagnoses of hyperuricemia, hypercalcemic nephropathy, glomerulosclerosis, and light-chain nephropathy are also possible.

Skeletal processes

Wide spread skeletal destruction is caused by a rapid increase in plasma cells. Skeletal destruction is accompanied with anemia, hypercalcemia, and osteolytic lesions. When the bone is destroyed, it is replaced by tumors which can lead to spinal cord compression, pathologic fracture, and pain. A compression fracture of the vertebral body can occur.

Neurologic processes

Skeletal destruction and nerve compression can cause spinal cord compression and/or radiculopathy.

There are no guidelines for prevention of multiple myeloma.

Multiple myeloma, also known as plasma cell myeloma, myeloma, myelomatosis, and Kahler’s disease, is part of an incapacitating spectrum of malignancies including monoclonal gammopathy of unknown significance (MGUS) and plasma cell leukemia. Typically a multiple myeloma involves the skeleton and bone marrow with malignant proliferation of plasma cells. This interferes with blood cell production leading to anemia, leukopenia, and thrombocytopenia. High levels of infection are common which can lead to the overproduction of certain antibodies. This causes amyloidosis, hyperviscosity, and renal failure. There are life extending treatments, but currently no cure.

Multiple myeloma is a cancer of certain blood cells - plasma cells and it occurs in both the skeletal system and bone marrow. If you have been diagnosed with multiple myeloma then you could be experiencing any of the following symptoms: anemia, bleeding, bone pain, hypercalcemia, infection (often pneumococcal), kidney failure, malaise, neuropathies, pathologic fractures, spinal cord compression, or weakness.

There are no known causes of multiple myeloma; however, certain individuals have an increased risk of developing it. You have an increased risk of developing the condition if you are over 65, male, African American, have a family member who has been affected, or have either Monoclonal Gammopathy of Uncertain Significance (MGUS) or plasmacytoma.

If you have multiple myeloma you will through what is called induction therapy. The first stage involves chemotherapy to destroy the cancer (this will typically destroy many healthy cells too). Once you have gone through a round of chemotherapy, and if you are under the age of 70 you may have some stem cells removed and frozen through a process known as autologous stem cell transplantation. Those stem cells will be used later to lengthen your survival. Some people will receive two rounds of stem cell transplantation 6 months apart. Some patients might also do a round of radiation therapy which involves shooting a beam of radiation directly at the affected area.

Multiple myeloma treatments can cause you to feel nauseous or experience decreased immunity. Biophosphate therapy increases your risk of osteonecrosis of the jaw (exposure of the jaw bone through lesions).

1. Yiin JH, Anderson JL, Daniels RD, Seel EA, Fleming DA, Waters KM, et al. A nested case-control study of multiple myeloma risk and uranium exposure among workers at the Oak Ridge Gaseous Diffusion Plant. Radiat Res. Jun 2009;171(6):637-45.
2. Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC. Multiple myeloma. Lancet. Jul 25 2009;374(9686):324-39.
3. Ludwig H, Durie BG, Bolejack V, Turesson I, Kyle RA, Blade J, et al. Myeloma in patients younger than age 50 years presents with more favorable features and shows better survival: an analysis of 10 549 patients from the International Myeloma Working Group. Blood. Apr 15 2008;111(8):4039-47.
4. Dimopoulos M, Kyle R, Fermand JP, et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood. May 5 2011;117(18):4701-5.
5. Durie BG, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. Sep 1975;36(3):842-54.
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