disclaimer participants have an implied responsibility to use the newly acquired information to...

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)


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.


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


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


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


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.


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


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.


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


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.


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.


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.


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.


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


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



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)



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)


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


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


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



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)



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.

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