disclaimer participants have an implied responsibility to use the newly acquired information to...
TRANSCRIPT
DISCLAIMERDISCLAIMERParticipants have an implied responsibility to use the newly acquired information
to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for
patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by
clinicians without evaluation of their patients’ conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s
product information, and comparison with recommendations of other authorities.
DISCLOSURE OF UNLABELED USEDISCLOSURE OF UNLABELED USEThis educational activity may contain discussion of published and
investigational uses of agents that are not indicated by the FDA. IMER does not recommend the use of any agent outside of the labeled indications. The
opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of IMER. Please refer to the official
prescribing information for each product for discussion of approved indications, contraindications, and warnings.
Disclosure of Conflicts of InterestDisclosure of Conflicts of InterestBeth Faiman, MSN, RN, APRN, BC, AOCNBeth Faiman, MSN, RN, APRN, BC, AOCN®®
Reported a financial interest/relationship or affiliation in the form of: Speakers’ Bureau, Celgene Corporation,
Millennium Pharmaceuticals, Inc.
Clinical Monitoring and Clinical Monitoring and InterpretationInterpretation
in Multiple Myelomain Multiple Myeloma
Multiple Myeloma Is…Multiple Myeloma Is…Like a Puzzle Like a Puzzle
Multiple factors to be considered at diagnosis and throughout
Not everyone presents the same way
Awareness of lab parameters and patient education are keys to success!
Faiman, 2008.
Multiple Myeloma Is…Multiple Myeloma Is…A Cancer of the Plasma Cells A Cancer of the Plasma Cells
Plasma cell malignancy characterized by an overproduction of abnormal immunoglobulin
Three main presentations
– Protein in serum
– Protein in urine
– Nonsecretory
Binucleated and eccentric bone marrow plasma cells
Stimson et al, 2009.
What Happens to the What Happens to the Immunoglobulin? Immunoglobulin?
Normal plasma cell that turns malignant; makes a “clone” of itself
Abnormal overproduction of one immunoglobulin
– Referred to as M protein, M spike
M protein is present in > 80% of patients
Excess amounts of abnormal proteins interfere with humoral immunity
M = monoclonal.Seidl et al, 2003; Nau et al, 2008.
Epidemiology and Risk FactorsEpidemiology and Risk Factors Prevalence
– Estimated new cases: 20,580 men and women
– Estimated deaths: 10,580 men and women
Risk factors
– Age: 70 years
– Gender: Males > females
– Race: Twice as many African-Americans as Caucasians
– Exposure to ionizing radiation
– Exposure to environmental toxins
– Immune system disorders
ACS, 2009; Horner et al, 2009.
Why Do Plasma Cells Turn Malignant?Why Do Plasma Cells Turn Malignant? Chromosomal changes and abnormalities
present in 80%–90% patients on FISH analysis
FISH: Looks at genes, chromosomes, and their aberrations
– 13q14 deletion, 17p13
Genomics is being used to understand the disease “drugable pathways”
– Prognosis
– Benefit of early/late treatment
FISH = fluorescent in situ hybridization.Chen et al, 2007.
Clinical Presentation Signs and Symptoms Clinical Presentation Signs and Symptoms General
– Back/bone pain (58%)
– Generalized weakness and fatigue
– Flu-like symptoms, nausea, vomiting (electrolytes)
– Easy bruising
– Recurrent infections
– Neurologic
• Headaches
• Blurred vision
• Ataxia
• Vertigo
• Neuropathy
– 20% of patients will be diagnosed based on routine laboratory examination but are asymptomatic!
Faiman, 2008; Faiman et al, 2008.
Subjective and ObjectiveSubjective and ObjectiveClinical Presentation Clinical Presentation
Physical exam findings
– Pallor-conjunctiva, mucous membranes due to anemia
– Tenderness over affected bony areas
– Altered mental status
– Incontinence, loss of sphincter tone, lower extremity weakness with pain may signify an oncologic emergency
– Tachycardia/arrhythmias due to electrolyte imbalance and associated renal impairment
Birgegard et al, 2005; Faiman, 2008.
Criteria for Diagnosis of Criteria for Diagnosis of Multiple MyelomaMultiple Myeloma
M plasma cells in bone marrow
M protein present in serum and/or urine
Myeloma-related organ dysfunction
– HyperCalcemia in serum (> 10.5 mg/L)
– Renal insufficiency (SCr > 2 mg/dL)
– Anemia (Hgb < 10 g/dL or 2 g < normal)
– Bone lesions or osteoporosis
SCr = serum creatinine concentration; Hgb = hemoglobin.Durie et al, 2003.
Hematologic Workup Hematologic Workup Laboratory analysis
– CBC and metabolic panel
• Calcium, uric acid, creatinine
• ALB, β2m, LDH
– M proteins
• SPEP, UPEP, immunofixation
• Quantitative immunoglobulin, sFLC assay
Radiologic imaging
– Skeletal survey
– Bone density
– MRI/CT or PET (more specific)
Bone marrow biopsy
CBC = complete blood count; ALB = albumin; β2m = β2microglobulin; LDH = lactose dehydrogenase; SPEP = serum protein electrophorosis; UPEP = urine protein electrophorosis; sFLC = serum free light chain; MRI = magnetic resonance imaging; CT = computed tomography; PET = positron emission tomography. NCCN, 2009a.
The Complete Blood Count: AnemiaThe Complete Blood Count: Anemia
Lab/Normal Reference Range Value
WBC: 3.0–11.0 k/uL 8.17
RBC: 4.2–6.0 m/uL 3.04 (L)
Hgb: 13.0–17.0 g/dL 9.3 (L)
Hct: 39.0%–51.0% 28.7 (L)
MCV: 80–100 fL 94.4
RDW-CV: 11.5%–15.0% 14.3
Plt: 150–400 k/uL 209
Neutrophil: 38.5%–75.0% 77.0 (H)
Absolute neutrophil: 1.00–7.50 k/uL 6.29
WBC = white blood cell; RBC = red blood cell; Hct = hematocrit; MCV = mean corpuscular volume;RDW-CV = red cell distribution width; Plt = platelet.
Lab values vary slightly amongst institutions and laboratories
AnemiaAnemia
A reflection of the bone marrow’s ability to produce cells that are obtained through peripheral blood draws
Anemia is a functional inability of the blood to supply the tissue with adequate oxygen for proper metabolic function
It is not a disease, but rather the expression of an underlying disorder or disease
NCCN, 2009a; Zarychanski et al, 2008.
Anemia (cont.)Anemia (cont.) Anemia
– Cytokine mediated or from crowded bone marrow
• High IL-6 levels will lead to blunted erythropoiesis and shortened red cell survival
– Chronic renal disease
– Microcytic or macrocytic anemia can be due to nutritional deficiencies or blood loss
• Vitamin B12
• Folate or iron deficiency
– MDS
IL = interleukin; MDS = myelodysplastic syndrome.Kauchansky, 2001; Miceli et al, 2008.
Anemia: Treatment OptionsAnemia: Treatment Options May result in fatigue, difficulty breathing, rapid
heartbeat, dizziness, depression or mood disturbances, weight loss, nausea, and difficulty sleeping
Treatment options for anemia
– Treat the myeloma: Many patients will show slow Hgb rise with improvement in renal function and decrease in tumor burden
– Erythropoietin
– Darbepoetin-α
• With caution (adhere to guidelines, VTE risk is increased)
– Transfusion if symptomatic
VTE = venous thromboembolism. NCCN, 2009b.
The Complete Blood Count: Anemia (cont.)The Complete Blood Count: Anemia (cont.)
Workup for anemia
– Ferritin
– TIBC
– Iron
– Folate
– MMA
– Vitamin B12
– Reticulocyte percentage (optional)
Lab/Normal Reference Range Value
Ferritin: 18.0–300.0 ng/mL 22
TIBC: 210–415 ug/dL 440
Iron: 30–140 ug/dL 99
Folate: 2–18 ng/mL > 18
MMA: 79–376 nmol/L 399
Vitamin B12: 221–700 pg/mL 200
TIBC = total iron binding capacity; MMA = methylmalonic acid.NCCN, 2009b.
Lab values vary slightly amongst institutions and laboratories
B12 Deficiency in Multiple MyelomaB12 Deficiency in Multiple Myeloma
B12 deficiency B12 < 200 pg/mL
B12 > 200 < 300 pg/mL and elevated MMA
Probable B12 deficiency B12 > 200 < 300 pg/mL and normal MMA
B12 > 300 pg/mL and elevated MMA
Baz et al, 2004.
The Complete Blood Count:The Complete Blood Count:CytopeniasCytopenias
Lab/Normal Reference Range Value
WBC: 4.0–11.0 k/uL 1.92
Plt: 150–400 k/uL 209
MPV: 9.0–12.7 fL 9.4
Neutrophil: 38.5%–75.0% 48.0 (L)
Absolute neutrophil: 1.00–7.50 k/uL 0.92 (L)
Lymphocyte: 15.9%–47.3% 35.5
Absolute lymphocyte: 1.00–4.00 k/uL 1.69
Leukopenia
Neutropenia
– Granulocyte percentage
– Absolute granulocyte
Thrombocytopenia
Lab values vary slightly amongst institutions and laboratories
Ohio State University Medical Center.
Neutropenia and InfectionNeutropenia and Infection
Neutropenia
– Functional neutrophils are critical to the immune system
– Neutropenia can occur from treatment or the disease itself
– Educate signs and symptoms of infection
Risk is primarily during times of low WBC or treatment with agents that lower immune function
Miceli et al, 2008.
Neutropenia and Infection (cont.)Neutropenia and Infection (cont.)
Prophylactic antibiotic usage for neutropenia is controversial– Generally not done except during high-dose
therapy (transplant setting) or if planned prolonged neutropenia in high-risk patients
Treatment – Colony-stimulating factors increase WBC
• Sargramostim• Filgrastim• Peg-filgrastim
– Treat the myeloma itself if disease related
Miceli et al, 2008.
InfectionInfection A major cause of death in patients with myeloma Impaired antibody formation after antigenic stimulation
or deficient antibody production
Impaired granulocyte function, bone marrow infiltration Most infections are in urinary/respiratory tracts
– Streptococcus pneumoniae, gram negative bacilli (GNB) Non-pharmacologic
– Wash hands, avoid people with colds, prompt reporting of symptoms
– Target to UTI/respiratory Pharmacologic
– IVIG
– Antibiotic prophylaxis: Herpes zoster, PCP, fungal infections
– Flu/pneumococcal vaccine polyvalent
– H1N1 vaccine
UTI = urinary tract infection; IVIG = intravenous immunoglobulin; PCP = pneumocystis pneumonia. Paradisi et al, 2001; Kollef, 2008; Gooskens et al, 2009; Ferguson et al, 2009; Pneumovax® prescribing information, 2009; Zostavax® prescribing information, 2009.
The Serum Complete The Serum Complete Metabolic PanelMetabolic Panel
Lab/Normal Reference Range Value
BUN: 8–25 mg/dL 22
Creatinine: 0.7–1.4 mg/dL 1.0
Calcium: 8.5–10.5 mg/dL 8.9
ALB: 3.5–5.0 g/dL 4.3
Alkaline phosphatase: 40–150 U/L 44
Indicators of myeloma related organ dysfunction on CMP
– BUN
– Creatinine
– Calcium
– ALB
– Alkaline phosphatase
CMP = complete metabolic panel; BUN = blood urea nitrogen.
Lab values vary slightly amongst institutions and laboratories
Renal InsufficiencyRenal Insufficiency
BUN
Creatinine
CrCL or eGFR are best indicators of renal function
– Accumulation of proteins can cause tubular damage
Note the angulated and tubular casts, surrounded by macrophages
Light-chain cast nephropathy
CrCL = creatinine clearance; eGFR = estimated glomerular filtration rate.Karstila et al, 2008; Tonelli, 2006.
Renal Insufficiency (cont.)Renal Insufficiency (cont.) Bence-Jones proteinuria: Incidence ~ 70%
– Light chain Igs can precipitate and damage renal cells
– Free light chains filtered in the nephron’s glomerulus, then absorbed and metabolized by proximal tubular cells
– Heavy and light chains can cause renal tubular damage
– sFLC assay more reliable than urine
– ATN secondary to NSAIDS, dehydration, nephrotoxic agents (CT dyes)
– Supportive therapy
• Hydration, correct underlying cause with treatment
• Avoid IV contrast and nephrotoxic agents (IV dyes, NSAIDS)
• Plasmapheresis, dialysis
ATN = acute tubular necrosis; NSAIDS = non-steroidal anti-anflammatory drugs.Rajkumar et al, 2001; Dimopoulos et al, 2008; Botchler et al, 2008; Wong et al, 2007.
Hypercalcemia and Bone Loss Hypercalcemia and Bone Loss Hypercalcemia in 15% of patients
– Increased calcium levels, dehydration can precipitate renal failure
– Treat with pamidronate, hydration, treat the disease
Pathobiology: Malignant cells produce osteoclast- activating factors that destroy bone cells
– Osteoclast stimulation leads to extensive osteolysis, severe bone pain, and pathologic fractures
– Spinal cord compression
– Plasmacytoma with significant bone destruction Most visible aspect of myeloma
– 80% of patients develop bone disease
Roodman, 2008.
Hypercalcemia of MalignancyHypercalcemia of Malignancy
Symptoms
– Altered LOC, constipation, coma
Diagnosis: Confirm by measuring CSC mg/dL
(4.0 – serum ALB g/dL) Serum calcium mg/dL + 0.8
Example
Calcium = 11.0 mg/dL
ALB = 3.0 mg/dL
4.0 - 3.0 = 1.0
a) Multiply (1.0) by 0.8, and add to the calcium of 11.0
CSC = 11.8 mg/dL
LOC = level of consciousness; CSC = corrected serum calcium.Payne, 2004.
Complete Metabolic Panel Complete Metabolic Panel May Signify Bone Loss May Signify Bone Loss
Osteolytic lesions occur adjacent to myeloma resulting in lytic bone pain and pathologic fractures
Bone destruction is caused by
– Growth of myeloma cells that push aside normal bone-forming cells
– Increased activity of osteoclasts (cells that normally break down old or damaged bone)
Treat: Radiotherapy, active treatment of underlying disease, analgesia, bisphosphonates, PT, and orthopedic interventions (vertebroplasty or balloon kyphoplasty)
PT = physical therapy.Silvestris et al, 2009; Heran et al, 2006.
A Circular Network of Cells That A Circular Network of Cells That Leads to Myeloma Bone DiseaseLeads to Myeloma Bone Disease
Myeloma
cells
Bone marrow
stroma
Osteoblast
Bone
Osteoclast
Mundy, 1991.Courtesy of Beth Faiman, MSN, RN, APRN, BC, AOCN®.
Osteoporosis: Osteoporosis: May Be Presenting FeatureMay Be Presenting Feature
Primary causes (most common in non-myeloma patients)
– Age, sex, race, postmenopausal status, smoking history, sedentary lifestyle, steroids, malabsorption (GI)
Secondary causes
– Malignancy
– Hyperparathyroidism
– Renal osteodystrophy from CRF
Diagnosis: BMD
GI = gastrointestinal; CRF = chronic renal failure; BMD = bone mineral density.Bonura, 2009; Licata, 2006.
Bone Mineral Density Bone Mineral Density T-score: Variance between patient and
young adult baseline• -1 is considered normal
• -1 and -2.5 osteopenia
• Below -2.5 is considered osteoporosis
Z-score: Age- and gender-matched control groups – The control group consists of other people in the
patient’s age group of the same size and gender
– Variances between the patients and control groups’ amount of bone
Bonura, 2009; Song et al, 2009.
Bone Mineral Density (cont.) Bone Mineral Density (cont.)
Patients may be diagnosed with myeloma due to a decline in BMD and abnormal Z-scores
– Important if no x-ray or plain film evidence of myeloma
Good to have as a baseline especially postmenopausal women, older males
Patients on steroid therapy
Sikon et al, 2006.
Bone Mineral Density – Example Case Bone Mineral Density – Example Case
Findings
– Spine: 0.63 g/cm2 (T-score -4.5, Z-score -3.5)
– Left femoral neck: 0.72 g/cm2 (T-score -2.1, Z-score -1.1)
– Total: 0.73 g/cm2 (T-score -2.2, Z-score -1.4.)
Impression
– Osteoporosis
Fracture risk
– Increased, secondary causes should be considered
Sikon et al, 2006; Licata, 2006.
National Osteoporosis FoundationNational Osteoporosis FoundationGuidelines for OsteoporosisGuidelines for Osteoporosis
Vitamin D recommendations for intake
– Adults under age 50 need 1,000 mg of calcium and 400–800 IU of vitamin D3 daily
– Adults 50 and over need 1,200 mg of calcium and 800–1,000 IU of vitamin D3
If the patient is taking bisphosphonates, continue with treatment guidelines
Optimal serum concentrations of 25-hydroxyvitamin D [25(OH)D] have not been defined but higher targets will likely be beneficial to decrease fracture risk
Faiman et al, 2008.
Skeletal Survey and MRISkeletal Survey and MRI
MRI of spine showing T6 wedge deformity
Skeletal survey (x-rays)
Osteolytic lesions
Courtesy of Beth Faiman, MSN, RN, APRN, BC, AOCN®.
Diagnosis of Skeletal Diagnosis of Skeletal Complications of MalignanciesComplications of Malignancies
Plain-film x-rays or radiography: Bone survey most reliable in myeloma
Bone scans will miss osteolytic lesions
MRI: Highly sensitive to bone metastases, spinal metastasis, soft tissue tumors
CT scan: Confirm suspicious findings raised on bone survey/scan
PET/CT scan
Roodman, 2008.
Whole-Body Whole-Body 1818F-FDG PETF-FDG PETScan and MyelomaScan and Myeloma
FDG is an analog of glucose that is radiolabeled with the positron-emitting radionuclide 18F
Metabolically active cells take up and phosphorylate FDG, which is not further metabolized, but remains trapped within the cell
Resulting intracellular accumulation of FDG is imaged with PET
High uptake is seen in tumor cells, with increased rates of metabolism compared with normal tissue
FDG = fluorodeoxyglucose.Bredella et al, 2005.
Whole-Body Whole-Body 1818F-FDG PETF-FDG PETScan and Myeloma (cont.)Scan and Myeloma (cont.)
Used to identify the extent and activity of multiple myeloma for staging and monitoring purposes
Distinguishes between active/inactive disease at various intervals
– Stem cell transplantation
– Extramedullary disease, plasmacytomas
Useful in combination with CT scans
Not standard of care for all yet
Durie et al, 2002.
Minimally Invasive Procedures for Minimally Invasive Procedures for VCFs Percutaneous VertebroplastyVCFs Percutaneous Vertebroplasty
VCFs = vertebral compression fractures.
Percutaneous Restore height Create void Low pressure fill
Correct kyphosis Restore stability Relieve pain in VCFs
Faiman, 2008; Dudeney et al, 2002.
Balloon KyphoplastyBalloon Kyphoplasty
Myeloma-Specific Clinical MonitoringMyeloma-Specific Clinical Monitoring
Serum ALB
Serum β2m
Lab/Normal Reference Range Value
ALB: 3.5–5.0 g/dL 3.2 (L)
β2m: 0.3–1.9 mg/L 6.2 (H)
ISS Stage Criteria
ISerum β2m < 3.5 mg/LSerum ALB ≥ 3.5 g/dL
II Serum β2m < 3.5 mg/LSerum ALB < 3.5 g/dL
OR
Serum β2m 3.5 to < 5.5 mg/L
III Serum β2m ≥ 5.5 mg/L
ISS = International Staging System.Kyle et al, 2009.
Lab values vary slightly amongst institutions and laboratories
SPEP and UPEP SPEP and UPEP SPEP: Lab/Normal Reference Range Value
Alpha 1 globulin: 0.11–0.22 gm/dL 0.13
Alpha 2 globulin 0.75
Beta globulin: 0.50–1.00 gm/dL 0.65
Gamma globulin: 0.60–1.35 gm/dL 2.09
M spike (g/dL) 2.37
UPEP: Lab/Normal Reference Range Value
Albumin, urine random (%) 2.9
Alpha 1 globulin, urine low: > 0% 1.7
Alpha 2 globulin, urine (%) 2.9
Beta globulin, urine (%) 7.6
Gamma globulin, urine (%) 84.9
Lab values vary slightly amongst institutions and laboratories
The Ohio State Medical Center.
Protein Electrophoresis Protein Electrophoresis
Protein electrophoresis
Normal SPEP Myeloma cells producing M spike
© 2004, 2000 Elsevier Inc. All rights reserved.
Serum Protein Electrophoresis Serum Protein Electrophoresis
SPEP with immunofixation
Immunofixation investigates abnormal bands (IgG)
Serum and urine are evaluated to improve detection
– Not performing a serum or urine evaluation could miss 10% of patients with hypogammaglobulinemia where the M spike is “hiding” under the gamma region and is undetected
Rajkumar et al, 2005; Denier et al, 2006.
Monoclonal Proteins and Monoclonal Proteins and Immunoglobulins Immunoglobulins
M proteins: Lab/Normal Reference Range Value
MPA serum IgG
717–1,411 mg/dL
4,300
MPA serum IgA
78–391 mg/dL
29
MPA serum IgM
53–334 mg/dL
24
MPA serum kappa
534–1,267 mg/dL
5,900
MPA serum lambda
253–653 mg/dL
< 30
Immunoglobulin structure
MPA = monoclonal protein analysis.The Ohio State Medical Center.
Lab values vary slightly amongst institutions and laboratories
Monoclonal Proteins and Immunoglobulins (cont.)Monoclonal Proteins and Immunoglobulins (cont.)
M Proteins: Lab/Normal Reference Range Value
MPA serum IgG
717–1,411 mg/dL
490 (L)
MPA serum IgA
78–391 mg/dL
32 (L)
MPA serum IgM
53–334 mg/dL
24 (L)
MPA serum kappa
534–1,267 mg/dL
480 (L)
MPA serum lambda
253–653 mg/dL
200 (L)
Hypogammaglobulinemia Just because the Ig is in the normal range we assume it is
functioning normally Some or all Igs are depressed
Rose et al, 2006.The Ohio State Medical Center.
Lab values vary slightly amongst institutions and laboratories
Serum Free Light ChainsSerum Free Light Chains
Normal Abnormal
Kappa light chain: 3.3–19.4 mg/L – Normal ratio for free light-chain
kappa: Lambda is 0.26–1.65
Elevation of kappa: Lambda ratio suggests kappa light chain M gammopathy is present
Lambda light chain: 5.7–26.3 mg/L – Kappa: Lambda free light-chain
ratio < 0.26 typically defined as having M lambda free light chain
Decreased in Kappa: Lambda ratio suggests lamba light chain M gammopathy is present
77.4 (H)
97.1 (H)
687.5 (H)
1,051.6 (H)
1,049.2 (H)
1,879.4 (H)
3,089.0 (H)
Increasing kappa sFLC
Dispenzieri et al, 2008; Hutchinson et al, 2008.The Ohio State Medical Center.
Lab values vary slightly amongst institutions and laboratories
24-Hour Urine for Protein 24-Hour Urine for Protein and Immunofixationand Immunofixation
24-Hour Protein: Lab/Reference Range Value
ALB 24-hour, urine (%) 20.4
Alpha 1 globulin 24-hour, urine low: > 0% 18.7
Alpha 2 globulin 24-hour, urine (%) 26.1
Beta globulin, urine (%) 12.9
Gamma globulin, urine (%) 21.9
Protein 24-hour, urine (low: < 0.16 gm) < 0.16
M spike quantity 24-hour 0.024
Dispenzieri et al, 2008.The Ohio State Medical Center.
Lab values vary slightly amongst institutions and laboratories
Bone Marrow Aspirate and BiopsyBone Marrow Aspirate and Biopsy
Adult red marrow has a large reserve capacity for cell production
Only found in the upper ends of the femur and humerus; flat bones of the sternum, ribs, cranium, pelvis, and vertebrae
Important to characterize plasma cell percentage, FISH, and cytogenetics
Hartman et al, 2004; Cook et al, 2006.
Diagnosis of Myeloma Diagnosis of Myeloma
Not everyone qualifies for the diagnosis of myeloma if a M protein is present
In fact, only a small percentage of individuals with a M protein in their serum or urine will need to be treated
Hutchinson et al, 2008.
How Often Are Labs Monitored? How Often Are Labs Monitored?
Newly diagnosed
Relapsed
At least monthly CBC and CMP
Bone marrow
Jardine, 2008.
Myeloma Agents Work Through Myeloma Agents Work Through Different MechanismsDifferent Mechanisms
Alkylating agents
– Melphalan
Anthracyclines
– Pegylated liposomal doxorubicin
Corticosteroids
– Dexamethasone, prednisone
IMiDs
– Thalidomide
– Lenalidomide
Proteasome inhibitors
– Bortezomib
IMiDs = immunomodulatory drugs.
Kyle et al, 2004.
Current Treatment Options Current Treatment Options Transplant candidate
– Bortezomib/dexamethasone
– Bortezomib/doxorubicin/dexamethasone
– Bortezomib/lenalidomide/dexamethasone
– Bortezomib/thalidomide/dexamethasone
– Dexamethasone
– Liposomal doxorubicin/vincristine/dexamethasone
– Lenalidomide/dexamethasone
– Thalidomide/dexamethasone
Non-transplant candidate
– Dexamethasone
– Lenalidomide/low-dose dexamethasone
– Liposomal doxorubicin/vincristine/dexamethasone
– Melphalan/prednisone/bortezomib
– Melphalan/prednisone/thalidomide
– Thalidomide/dexamethasone
– Vincristine/doxorubicin/dexamethasone
NCCN, 2009a.
Current Treatment Options (cont.)Current Treatment Options (cont.)
Maintenance
– Interferon
– Steroids
– Thalidomide
– Controversial; many ongoing studies
Supportive Care Plan for Supportive Care Plan for Patients With Multiple MyelomaPatients With Multiple Myeloma
1) What are the appropriate lab tests?
2) Are they a candidate for ESAs?
3) Is your patient on bisphosphonates?
4) Would they benefit from a flu/pneumococcal vaccine polyvalent? HSV prophylaxis?
5) Does your patient need VTE prophylaxis?
6) What is the patient education interval of follow- up, side-effects of therapy, and prompt reporting of symptoms?
ESAs = erythropoiesis-stimulating agents; HSV = herpes simplex virus.Pneumonax® prescribing information, 2009; Karten, 2007; Rome et al, 2008.
Case Study 1Case Study 1 Mr. B is a 55-year-old man who started to notice
fatigue late in the day over a period of two months
Pain in his right femur
Subjective
– Developed acute onset of lower back pain when mowing the lawn, rated 10/10
– Nothing alleviated the pain, so he went to the emergency room
History
– No contributing medical history
– No prior back trauma or pain
Case Study 1: Lab ValuesCase Study 1: Lab Values
Lab/Normal Reference Range Value
WBC: 3.0–11.0 k/uL 5.44
Plt: 150–400 k/uL 99 (L)
Hgb: 13.0–17.0 g/dL 8.3 (L)
Hct: 39.0%–51.0% 22.9 (L)
MCV: 80–100 fL 94.4
RDW-CV: 11.5%–15.0% 14.3
Neutrophil: 38.5%–75.0% 52.0
Absolute neutrophil: 1.00–7.50 k/uL 2.97
Lab/Normal Reference Range Value
BUN: 8–25 mg/dL 66
Creatinine: 0.7–1.4 mg/dL 2.4 (H)
Calcium: 8.5–10.5 mg/dL 11.9 (H)
ALB: 3.5–5.0 g/dL 3.0 (L)
Alkaline phosphatase: 40–150 U/L 156 (H)
β2m 6.9 (H)
Lab values vary slightly amongst institutions and laboratories
The Ohio State Medical Center.
Case Study 1: Lab Values (cont.)Case Study 1: Lab Values (cont.)
SPEP: Lab/Normal Reference Range Value
Alpha 1 globulin: 0.11–0.22 gm/dL 0.24
Alpha 2 globulin 0.78
Beta globulin: 0.50–1.00 gm/dL 0.63
Gamma globulin: 0.60–1.35 gm/dL 9.33
M spike (g/dL) 9.20 (H)
Lab/Normal Reference Range Value
MPA serum IgG
717–1,411 mg/dL
10,300
MPA serum IgA
78–391 mg/dL
29
MPA serum IgM
53–334 mg/dL
24
MPA serum kappa
534–1,267 mg/dL
15,500
MPA serum lambda
253–653 mg/dL
< 30
Lab values vary slightly amongst institutions and laboratories
The Ohio State Medical Center
Case Study 1: Bone SurveyCase Study 1: Bone Survey Skull is unremarkable. Axial skeleton is intact, no fracture present. Chest
cage is intact.
Long bones of the upper extremity and bony pelvis are intact.
A large 5 cm radiolucency identified within the proximal aspect of the right femur of the level of the lesser trochanter with minimal scalloping of the lateral cortex
There is widespread osteopenia. Otherwise long bones of the lower extremities are intact.
Impression
– Lytic lesion in the proximal right femur
– Findings consistent with multiple myeloma
– Clinical correlation is necessary
Case Study 1: Final DiagnosisCase Study 1: Final Diagnosis
Bone marrow, aspirate smear and core biopsy, with clot section and peripheral blood
– Involved by a plasma cell neoplasm with approximately 20% plasma cells
– Hypocellular bone marrow (20%) with trilineage hematopoiesis and erythroid predominance
– Stainable iron present
Immunohistochemical stains for CD138, kappa and lambda demonstrate lambda monotypic plasma cells that represent approximately 20% of the total cellularity
Cytogenetics: Normal male chromosome
– FISH is negative for 17p, del(13), and t(4:14)
Case Study 2Case Study 2 66-year-old grandmother
Diagnosis in 2004
Received lenalidomide and dexamethasone on clinical trial
Remains on lenalidomide 10 mg Days 1–21
Seen every two months
Feeling more “tired”
Exam
– Blood pressure: 142/76
– Pulse: 102
– Respiration: 16
– Temperature: 98.7
• No significant findings except for mid-thoracic back pain on palpation
Case Study 2: Lab ValuesCase Study 2: Lab Values
Lab/Normal Reference Range Value
WBC: 3.0–11.0 k/uL 2.44
Plt: 150–400 k/uL 99 (L)
Hgb: 13.0–17.0 g/dL 9.3 (L)
Hct: 39.0%–51.0% 28.2 (L)
MCV: 80–100 fL 102
RDW-CV: 11.5%–15.0% 17.3
Neutrophil: 38.5%–75.0% 66.0
Absolute neutrophil: 1.00–7.50 k/uL 1.61
Lab/Normal Reference Range Value
BUN: 8–25 mg/dL 28
Creatinine: 0.7–1.4 mg/dL 1.4
Calcium: 8.5–10.5 mg/dL 10.4 (H)
ALB: 3.5–5.0 g/dL 3.2 (L)
Alkaline phosphatase: 40–150 U/L 125
β2m 5.5 (H)
Lab values vary slightly amongst institutions and laboratories
The Ohio State Medical Center.
Case Study 2: Bone SurveyCase Study 2: Bone Survey All bone structures are osteopenic
Skull shows small calvarial lesions (unchanged in appearance from last exam)
AP and lateral views of the thoracic and lumbar spine show diffuse severe osteopenia and multiple compression fractures involving the majority of the thoracic and lumbar vertebrae
Long bones of the upper extremety show lesions with the largest measuring 1.3 cm that is not abutting the cortex
The bony pelvis show scattered lucencies more prominent than prior exam
Several small radiolucencies are identified within the proximal aspect of the left femur and with minimal scalloping of the lateral cortex
No other lesions are noted
Impression
– Widespread osteopenia
– Multiple lytic lesions noted throughout the largest measuring 1.3 cm
– Findings are consistent with disease progression compared to the last study
Trend: Kappa sFLC every 3 months
24.2 (H)
22.5 (H)
19.4 (H)
19.3 (H)
34.5 (H)
31.1 (H)
432.1 (H)
400.7 (H)
953.0 (H)
Case Study 2: Final DiagnosisCase Study 2: Final Diagnosis
Bone marrow biopsy was not repeated
Her labs and skeletal survey suggest progressive disease
Key Takeaways Key Takeaways
Multiple myeloma is an incurable, chronic disease
Palliation of symptoms and prevention of organ damage is essential to patient quality of life
Nurses play a critical role in the recognition of lab values and signs of disease
Patients who are educated will take an active role in their treatment which may improve outcomes
Cook, 2008; Rome et al, 2008; NCCN, 2009a.