The International Myeloma Foundation's
Nurse Leadership Board
WELCOMES YOU TO THIS
EDUCATIONAL TELECONFERENCE!
This program is supported by a grant from Celgene Corporation
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International Myeloma Foundation
Founded in 1990
Mission:
To improve the quality of life for myeloma patients
while working toward prevention and a cure
-Dr. Brian Durie & Susie Novis
Four areas of focus:
Education
Research
"Until there is a Cure...
There is the IMF."
Support
Advocacy
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International Myeloma Foundation
Membership ­ more than 195,000 globally
Global reach - 113 countries
Scientific Advisory Board
72 world recognized experts
Research Grant Award
Raised more than $50 million dollars
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Housekeeping
·
There are no prerequisites or fees for participating in and receiving
credit for this activity. Participants must 1) study the educational
activity, 2) download the posttest from the link provided in the
confirmation email, complete the posttest by recording the best
answer to each question in the answer key on the form, 3) complete
the evaluation form, 4) mail, e-mail or fax the completed form to
Medical Education Resources at
·
Mail: Medical Education Resources 1500 W. Canal Court, Building B
Littleton, CO 80120-6404
·
Fax: 720-449-0217
·
E-mail: Kathryn Holland, kathryn@mer.org
·
A statement of credit will be issued only upon receipt of a completed
activity evaluation form and a completed posttest with a score of 70%
or better. Statements of credit will be mailed within 6 weeks of the
activity.
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Consensus on Care:
Management of Side Effects of Novel Therapies
Presented by
Beth Faiman, RN, MSN, APRN-BC, AOCN®
Adult Nurse Practitioner
Cleveland Clinic
Cleveland, Ohio
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International Myeloma Foundation's Nurse
Leadership Board
For optimal therapy, adherence, and quality of life, MM patients
need education and support.
Nurses from leading multiple myeloma (MM) institutions formed a
Nurse Leadership Board (NLB) in collaboration with and under the
sponsorship of the International Myeloma Foundation (IMF) with
the express purpose of determining the unmet needs of MM
patients and developing action plans to address those needs.
IMF-NLB Board Mission based upon a Nurse Centric Model
Adapted from NLB Consensus Statement: CJON Supplement. 2008; Vol 12.
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IMF-NLB Nurse Educational Teleconference
Learning Objectives
Gain insights on novel therapies in multiple myeloma and their key
emergent side effects:
· Discuss critical issues in nursing management
· Explore medical implications of major emergent side effects
· Understand optimal management of emerging side effects
· Discuss the International Myeloma Foundation's Nurse Leadership
Board Consensus Statements
· Understand the clinical value of the Consensus Statements
· Explore unification of the nursing community behind one standard
of care
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Multiple Myeloma ­
A Cancer of Plasma B Cells
· Characterized by bone marrow and plasma cell pathology
· Abnormal monoclonal immunoglobulin (M protein/paraprotein) produced
· Bone marrow function is decreased
Kyle, et al. New England Journal of Medicine. 2004.; San Miguel JF, et al. Clinical Care Options. Available at:
8
http://clinicaloptions.com/Oncology/Treatment%20Updates/Myeloma/Modules/Pathophysiology/Pages/Page%203.aspx. Accessed 22 February, 2007.
Multiple Myeloma: A Current Perspective
· MM Background
­ Etiology of MM
­ Epidemiology of MM
­ Biology of Disease
­ Diagnosis and Staging of MM
· Novel MM Therapies
· Adverse Events of Novel MM Therapies
· Nurse Management of Emergent Side Effects
· Clinical Utility of NLB Recommendations
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Multiple Myeloma:
Plasma Cell Pathology
Myeloma cells are distinguished from normal plasma cells
by the presence of large nuclei that are often eccentric.
© Phototake 2008
Adapted from NLB Consensus Statement: CJON Supplement. 2008; Vol 12.
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Multiple Myeloma: Epidemiology
· Incidence and rates
­ 1.4% of all cancers
­ 2nd most common (15%) of hematologic malignancies
· Approximately 20,580 estimated diagnoses in 2009
· Approximately 10,580 estimated deaths in 2009
· More than 80% of affected patients >age 60
­ Average age at diagnosis is 62 years for men and 61
years for women
­ 4% of cases are diagnosed in individuals <45 years
· Male vs Female (1.3:1)
· African Americans vs Caucasians 2:1
· Increasing incidence and earlier age of onset
Merck Manual Professional. 2005.; George, et al. American Family Physician. 1999.; American Cancer Society's Cancer Facts and
11
Figures. 2009.
Etiology of Multiple Myeloma
Cause of MM is not known.
Several factors are believed to contribute:
·
Decline in immune function
·
Biologic factors
·
Certain occupations (petroleum, textile, rubber
industries, etc)
·
Exposure to certain chemicals (eg, agricultural
chemicals, Agent Orange)
·
Exposure to ionizing radiation
·
Viruses (eg, HIV, hepatitis, herpes virus 8, etc)
Sheridan. Sem Oncol Nurs. 1996.
12
Major Symptoms at Diagnosis
· Bone pain 58%
· Fatigue 32%
· Weight loss 24%
· Paresthesias 5%
· Asymptomatic 11%
13
Kyle. Mayo Clinic Proceedings. 2003.
Common Sites for Bone Involvement
Skull
Spine
· Thoracic
· Lumbar
· Cervical
Pelvis
Long bones
Spinal cord compression can
occur
http://www.emedicine.com/Radio/topic460.htm#section~Introduction
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Diagnostic Evaluation of
Multiple Myeloma
Test
Finding(s) With Myeloma
CBC with differential counts
Hgb, WBC, platelets
Electrolytes
Creat, Ca+, Uric acid, Alb
Serum electrophoresis with quantitative
M protein in serum, may have levels of normal
immunoglobulins
antibodies
Immunofixation
Identifies light/heavy chain types M protein
-microglobulin
Levels (measure of tumor burden)
2
C-reactive protein
Levels (marker for myeloma growth factor)
24-hour urine protein electrophoresis
Monoclonal protein (Bence Jones)
Bone marrow biopsy
10% plasma cells
Skeletal imaging
Osteolytic lesions, osteoporosis
Serum free light chain
Free light chains
MRI
Focal disease, plasmacytoma
Alb = albumin; CBC = complete blood count; Creat = creatinine; Hgb = hemoglobin; MRI =
magnetic resonance imaging; WBC = white blood cell
Abella. Oncology News International. 2007.; Barlogie, et al. Williams Hematology. 2006.; Durie, et al. Hematology Journal. 2003.;
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MMRF. Multiple Myeloma: Disease Overview. 2006. www.multiplemyeloma.org; Rajkumar, et al. Blood. 2005.
Criteria for Diagnosis of
Multiple Myeloma
Monoclonal plasma cells present in the bone marrow
10%, and/or presence of a documented plasmacytoma
+
Presence of M component in serum and/or urine
+
One or more of the following (CRAB criteria)
· Calcium elevation (serum calcium >11.5 mg/dL)
· Renal insufficiency (serum creatinine >2 mg/dL)
· Anemia (hemoglobin <10 g/dL, or 2 g/dL <normal)
· Bone disease (lytic lesions or osteopenia)
Durie, et al. Leukemia. 2006.
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Durie-Salmon Staging System
for Multiple Myeloma
Myeloma cell mass
Stage
Criteria
(×1012 cells/m2)
I
All of the following:
<0.6 (low)
Hemoglobin >10 g/dL
Serum calcium level 12 mg/dL (normal)
Normal bone or solitary plasmacytoma on
x-ray
Low M component production rate:
IgG <5 g/dL
IgA <3 g/dL
Bence Jones protein <4 g/24 hr
II
Not fitting stage I or III
0.6 to 1.2 (intermediate)
III
One or more of the following:
>1.2 (high)
Hemoglobin <8.5 g/dL
Serum calcium level >12 mg/dL
Multiple lytic bone lesions on x-ray
High M-component production rate:
IgG >7 g/dL
IgA >5 g/dL
Bence Jones protein >12 g/24 hr
Subclassification Criteria
A
Normal renal function (serum creatinine level <2.0 mg/dL)
B
Abnormal renal function (serum creatinine level 2.0 mg/dL)
Durie, et al. Cancer. 1975.
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International Staging System for
Symptomatic Multiple Myeloma
STAGE
VALUES
ß M <3.5 mg/dL
Stage 1
2
ALB 3.5 g/dL
Stage 2
Not Stage 1 or 3
Stage 3
ß M >5.5 mg/dL
2
M=serum microglobulin in mg/dL; ALB=serum albumin in g/dL
2
2
Greipp, et al. Blood. 2005.
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Challenges in Multiple Myeloma Management
· Incurable in most patients
· Autologous stem cell transplant may
prolong progression free survival,
but is not curative
· Treatment of relapse
­ No standard therapy
· New treatment options needed
Rajkumar, et al. Mayo Clinic Proceedings. 2002.
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MM Treatment Options
Conventional chemotherapy:
·
Melphalan
·
Doxorubicin
·
Cyclophosphamide
Steroid therapy:
·
Dexamethasone
·
Prednisone
Novel therapeutics:
·
THALOMID® (thalidomide)
·
REVLIMID® (lenalidomide)
·
VELCADE® (bortezomib)
Stem cell transplantation:
·
Autologous
·
Allogeneic
Radiation therapy
Thalomid ® Prescribing Information; Revlimid ® Prescribing Information; Velcade® Prescribing
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Information; http://www.nccn.org/professionals/physician_gls/PDF/myeloma.pdf.
Novel Therapies for Multiple Myeloma
THALOMID® (thalidomide)
REVLIMID® (lenalidomide)
VELCADE® (bortezomib)
Benefits and Challenges
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Novel Therapy-THALOMID® (Thalidomide)
THALOMID® in combination with dexamethasone is indicated for
the treatment of patients with newly diagnosed multiple myeloma.
Mechanism of Action
· Immunomodulatory
· Anti-inflammatory
· Anti-angiogenic agent
· Suppresses production of TNF-, IL-6, and other cytokines
http://www.thalomid.com/pdf/Thalomid_Pl.pdf
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THALOMID® (Thalidomide) + Dexamethasone
Most Commonly Reported Adverse Events
Most Commonly Reported Effects
n % Patients
Most Commonly Reported Effects
n % Patients
>20% for all grades
(n=204)
>20% for all grades
Metabolic
Hematological
Hyperglycemia
73
Anemia
78
Hypocalcemia
72
Leukopenia
35
Hyponatremia
43
Neutropenia
31
Hypokalemia
23
Thrombocytopenia
24
Neurology
Gastrointestinal
Neuropathy-sensory
54
Constipation
55
Confusion
28
Anorexia
28
Anxiety/Agitation
26
Nausea
28
Tremor
26
Cardiovascular
Insomnia
23
Edema
57
Depression
22
Thrombosis/embolism
23
Peripheral neuropathy-motor
22
Pain
Constitutional Symptoms
Bone
30
Fatigue
70
Other pain
25
Fever
24
Pulmonary
Weight loss
23
Dyspnea
42
Weight gain
22
http://www.thalomid.com/pdf/Thalomid_Pl.pdf
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Novel Therapy: Lenalidomide (REVLIMID®)
REVLIMID® in combination with dexamethasone is indicated for
use in patients with multiple myeloma who have had at least
one prior therapy.
Mechanism of Action
· Immunomodulatory agent with anti-angiogenic and
anti-neoplastic properties
· Inhibits the secretion of pro-inflammatory cytokines
· Increases the secretion of anti-inflammatory cytokines
http://www.revlimid.com/pdf/REVLIMID_PI.pdf
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REVLIMID® (Lenalidomide) Most
Commonly Reported Adverse Events*
Most Commonly Reported Side
n % Patients
Effects > 20% for all Grades
(n=346)
Constipation
39
Fatigue
38
Insomnia
32
Muscle Cramp
30
Diarrhea
29
Neutropenia
28
Anemia
24
Loss/Lack of Strength
23
Fever
23
Nausea
22
Headache
21
Peripheral Edema
21
Dizziness
21
*REVLIMID® treatment in combination with dexamethasone
http://www.revlimid.com/pdf/REVLIMID_PI.pdf
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Novel Therapy: Bortezomib (VELCADE®)
VELCADE® for injection is indicated for the treatment of patients
with Multiple Myeloma
Mechanism of Action
· The first drug in the class of "proteasome inhibitors"
Reversible inhibitor of 26S proteasome complex
· Influences following pathways:
Apoptosis
Cell adhesion
Angiogenesis
Source: http://www.mlnm.com/products/velcade/full_prescrib_velcade.pdf
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VELCADE® (Bortezomib) Most Commonly
Reported Adverse Events
Most Commonly Reported
Patients (n=331)
Side Effects >15% for all Grades
n%
Asthenic conditions (fatigue, malaise, weakness)
61
Diarrhea
57
Nausea
57
Constipation
42
Peripheral neuropathy
36
Vomiting
35
Pyrexia
35
Thrombocytopenia
35
Psychiatric disorders
35
Decreased appetite and anorexia
34
Parasthesia and dysesthesia
27
Anemia
26
Headache
26
Cough
21
Dyspnea
20
Neutropenia
19
Rash
18
Insomnia
18
Abdominal pain
16
Bone pain
16
Source: http://www.mlnm.com/products/velcade/full_prescrib_velcade.pdf
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Consequences of Inadequately Managed
Side Effects
Psychological Impact
Physiological Impairment
Reduced Adherence
Lowered self-esteem,
Adverse side effects that
Therapy-associated side
anxiety, and depression,
are not properly managed
effects lead to a reduction
which will adversely impact
may lead to a variety of
in patient's desire and
the patient's overall health
physiological impairments
ability to adhere with
dosing schedules
Social Consequences
Lower Persistence
Reduced Efficacy
Reduced ability to function
Patients are less inclined
Adverse side effects may
optimally within
to remain on a therapy for
lead to premature stopping
relationships, work, and
which side effects are not
of medication or reduction
other social contexts
adequately managed
of dosage to a sub-
therapeutic level
Effective management of side effects improves
response outcomes and patient's quality of life
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IMF-NLB's Consensus Guideline
Supplement Publication
Adapted from NLB Consensus Statement: CJON Supplement. 2008; Vol 12.
29
Moving Toward Consensus
An NLB Assessment Survey Determined the Five Most
Common Emergent Side Effects Requiring Specific
Consensus Recommendation Development
Peripheral Neuropathy
DVT and PE
Myelosuppression
GI Effects
Steroid Effects
Adapted from NLB Consensus Statement: CJON Supplement. 2008; Vol 12.
30
Overview of Myelosuppression:
Definition and Symptoms
Anemia
Red Blood Cells
­ Lower than normal
number of red
blood cells
Lymphocyte
­ Fatigue, malaise
and SOB
Monocyte
Marrow
Neutropenia
White Blood Cells
Eosinophil
­ Lower than normal
number of white
blood cells
Basophil
­ Increased risk of
bacterial, fungal, and
Neutrophil
viral infections
Thrombocytopenia
Platelets
­ Platelet count less than
100 x 109/L
­ Bruising and bleeding
http://www.schneiderchildrenshospital.org/peds_html_fixed/peds/transplant/bonetran.htm; Adapted from NLB Consensus Statement:
31
CJON Supplement. 2008; Vol 12.
Risk of Grade 3 and 4 Myelosuppression
With Novel Therapies
Therapy
Patient
Anemia
Neutropenia
Thrombocytopenia
Population (N)
% N
% N
% N
THALOMID®
Newly
(thalidomide) +
diagnosed
16
13
4
dexamethasone
(102)
REVLIMID®
At least 1 prior
(lenalidomide) +
therapy
8
21
10
dexamethasone
(346)
1-3 prior
VELCADE®
therapies
10
15
29
(Bortezomib)
(331)
Grading based upon
Common Terminology Criteria for Adverse Events (CTCAE) v3.0
Adapted from NLB Consensus Statement: CJON Supplement. 2008; Vol 12.Thalomid® Prescribing Information; Revlimid® Prescribing Information;
Velcade® Prescribing Information; http://ctep.cancer.gov/forms/CTCAEv3.pdf
32
Managing Myelosuppression:
REVLIMID® (Lenalidomide)
Management of Anemia
If anemia judged related to lenalidomide therapy
Recommended Course
Occurs at Grade 3 or 4 (<8.0 g/dL)
Hold treatment
Has resolved to Grade 2 (<10.0 to 8.0 g/dL)
Restart at the next lower dose level from previous dose
Management of Neutropenia
When ANC
Recommended Course
Absolute neutrophils fall to <1.0 x 109/L
Interrupt REVLIMID® (lenalidomide) treatment, consider G-CSF, follow
CBC weekly
Return to >1.0 x 109/L and neutropenia is the only
toxicity
Resume REVLIMID® (lenalidomide) at 25 mg daily or previous dose if
lower*
Resume REVLIMID® (lenalidomide) at 15 mg daily or previous dose if
Return to >1.0 x 109/L and other toxicites present
lower*
For each subsequent drop below <1.0 x 109/L
Interrupt REVLIMID® treatment
Return to >1.0 x 109/L
Resume REVLIMID® (lenalidomide) at 5 mg less than the previous dose*
Management of Thrombocytopenia
When Platelets
Recommended Course
Fall to <30,000/mm3
Interrupt REVLIMID® (lenalidomide) treatment, follow CBC weekly
Return to >30,000/mm3
Restart REVLIMID® (lenalidomide) at 15 mg daily
For each subsequent drop <30,000/mm3
Interrupt REVLIMID® (lenalidomide) treatment
Return to >30,000/mm3
Resume REVLIMID® (lenalidomide) at 5 mg less than the previous dose*
*Do not dose below 5 mg daily
Revlimid® Prescribing Information
33
Adapted from NLB Consensus Statement: CJON Supplement. 2008; Vol 12.
Managing Myelosuppression:
VELCADE® (Bortezomib)
Management of Anemia
If anemia judged related to therapy
Recommended Course
Onset of Grade 4 toxicity (<6.5 g/dL)
Hold treatment
Once toxicity has resolved
Treatment may be restarted at a 25% reduced dose
Management of Neutropeniaa
When ANC
Recommended Course
Falls to onset of Grade 4 toxicity (<0.5 x
Therapy should be held
109/L)
Once toxicity has resolved
Treatment may be restarted at a 25% reduced dose
Management of Thrombocytopeniaa
When Platelets
Recommended Course
Fall to onset of Grade 4 toxicity (<25 x 109/L)
Hold therapy. Transfusion is recommended at the
discretion of the physician, particularly with any signs of
bleeding
Once toxicity has resolved
Treatment may be restarted at a 25% reduced dos.
aA decrease is anticipated in the neutrophil count during the treatment period (days 1­11), with rapid
return to baseline during the rest period (days 12 to 21). No evidence exists of cumulative
neutropenia or thrombocytopenia.
VELCADE Prescription Information; Lonial, et al. Blood. 2005. Millennium Pharmaceuticals, Inc., 2006. Adapted from NLB Consensus
34
Statement: CJON Supplement. 2008; Vol 12.
Overview of Thromboembolic Events (TE)
Consensus Statement
Cancer patients have a higher risk of TE events (blood clots), which may
lead to:
·
Deep vein thrombosis (DVT)
·
Pulmonary embolism (PE)
MM patients are at an increased risk for blood clots:
·
Patients are at increased risk with high-dose dexamethasone treatment
·
The risk for DVT/PE is further increased in patients treated with:
­
Thalidomide
­
Lenalidomide
­
Pegylated liposomal doxorubicin
Measures to prevent novel therapy-associated TE events include:
·
Mechanical
·
Myeloma regimen-related
·
Anticoagulant therapy (clot-preventing)
TE events are serious and potentially life-altering and life-threatening
Adapted from NLB Consensus Statement: CJON Supplement. 2008; Vol 12.
35
Qaseem, et al. Annals of Family Medicine. 2007.; Segal, et al. Annals of Family Medicine. 2007.;
htt
//
hlbi ih
/h
lth/d i/Di
/D t/DVT Wh I AtRi k ht
TE: Risk Factors
Individual Factors
Genetic Factors
Disease or Medical Conditions
Procedure Related
· Older Age
· Strong Family History TE
· Previous TE
· Current or Previous-
Central Venous
· Obesity
· Blood-clotting Disorders
· Cardiac Disease (MI, CHF)
Catheter
· Immobilization
Factor V Leiden Mutations
· Chronic Renal Disease and
Factor VIII Elevation
· IV Catheter
Nephrotic Syndrome
· Smoker/tobacco
Prothrombin Mutations
· Pacemaker
use
· Neurologic Disease
Protein C Deficiency
· Recent Surgery
· Varicose veins
Protein S Deficiency
· Stroke with paralysis
Hyperhomocysteinemia
·General
· Pregnancy
· Hospitalization within 3 mos w/ or
Sickle Cell Disease or Trait
·Orthopedic
w/o surgery
·Neurological
· Trauma
·GYN
· Diabetes
· Anesthesia
· Acute infection
· Hepatic disease
· Regional Bulky Lymphadenopathy
w/ extrinsic vascular compression
· Autoimmune Diseases
(rheumatologic, inflammatory
bowel diseases)
· Cancer/Chemotherapy
· Multiple Myeloma
Austin, et al. Blood. 2007.; Bauer. Annals of Internal Medicine. 2001.; Heit, et al. Archives of Internal Medicine. 2000.; Joffe, et al. Circulation. 2004.; Khorana, et al. Journal of Clinical
Oncology. 2006.; National Comprehensive Cancer Network, 2007.; Palumbo, et al. Leukemia. 2008.; Prandoni. Hematology. 2005; Prandoni, et al. Lancet Oncology. 2005.; Spencer, et al.
36
Archives of Internal Medicine. 2007; Gerpen, et al. Archives of Internal Medicine. 2004.
TE: Medications Risk Factors
· Hormone Replacement Therapy
· Oral Contraceptives
· Tamoxifen or Raloxifene
· Diethylstilbestrol
· Vitamin K
· Chemotherapy
· Anti-Myeloma Agents
· Supportive Therapies-Growth Factor Injections
Austin, et al, 2007; Bauer, 2001; Heit, et al, 2000, 2002; Joffe, et al, 2004; Khorana, et al, 2006; National Comprehensive Cancer Network, 2007;
37
Palumbo, et al, 2008; Prandoni, 2005; Prandoni, et al, 2005; Spencer, et al, 2007; Ven Gerpen & Mast, 2004.
TE Risk Factors: Anti-Myeloma Agents
Therapy
Increased Risk Factors
REVLIMID®
· High-Dose Dexamethasone (480 mg/m)
(lenalidomide)
· Erythropoietin (epo)
· Dexamethasone + epo
· Melphalan
· Melphalan + Prednisone
· Cyclophosphamide
· Doxorubicin / pegylated liposomal doxorubicin ± Dexamethasone
· Doxorubicin/ pegylated liposomal doxorubicin + 2 or more
chemotherapies ± corticosteroid
THALOMID®
· High-Dose Dexamethasone
(thalidomide)
· Epo
· Melphalan ± Prednisone
· Doxorubicin / pegylated liposomal doxorubicin ± Dexamethasone
· Doxorubicin / pegylated liposomal doxorubicin + 2 or more
chemotherapies ± corticosteroid
VELCADE®
· In combination with some multi-drug combos
(bortezomib)
Barlogie, et al, 2005; Bennett, et al, 2006, 2007; Celgene Corporation, 2007a, 2007b; Harousseau, et al, 2006; Hussein, 2006; Knight, et al, 2006; Lonial, et al, 2007; Manochakian, et al, 2007;
38
Millennium Pharmaceuticals, Inc, 2007; Offidani, et al, 2005; Ortho Biotech Products, LP, 2007; Palumbo, et al, 2008; Richardson, et al, 2007; Zangari, et al, 2002.
DVT: Signs/Symptoms
· Slight Fever
· Tachycardia
· Unilateral swelling, erythema, warm extremity
· Cyanosis and cool skin if arterial obstruction
· Dull ache, pain, tight feeling over area & with
palpation
· + Homans' Sign (35% pts)
· Obvious swelling (may not be present early)
· Distension of superficial venous collateral vessels
http://www.nhlbi.nih.gov/health/dci/Diseases/Dvt/DVT_SignsAndSymptoms.html
39
Adapted from NLB Consensus Statement: CJON Supplement. 2008; Vol 12.
PE: Signs/Symptoms
· Anxiety
· Sudden dyspnea
· Chest discomfort-increases w/ breathing
· Tachycardia or tachypnea
· Low-grade fever
· Pleural friction rub, crackles followed by
diminished breath sounds, wheezing
· ECG right axis deviation or new RBBB
PE is a Medical Emergency
http://www.nhlbi.nih.gov/health/dci/Diseases/Dvt/DVT_SignsAndSymptoms.html; Story, Clinical manual for the oncology advanced practice nurse. 2006; Van
40
Gerpen, et al. Clinical Journal of Oncology Nursing 2004.; Adapted from NLB Consensus Recommendations: CJON Supplement Vol 12. 2008.
TE: Diagnostic Tests
DVT
PE
· Doppler Ultrasound
· Ventilation Perfusion Lung
(VQ) Scan
· Contrast Venography *
· Spiral CT Scan *
· D-Dimer
· Pulmonary Angiography *
· Antithrombin Level
· D-Dimer
· Antithrombin Level
To maintain therapeutic level INR 2-3
* Use caution as contrast dye may cause or worsen renal impairment
http://www.nhlbi.nih.gov/health/dci/Diseases/Dvt/DVT_Diagnosis.html; Qaseem, et al. Annals of Family Medicine 2007. ; Story. Clinical
manual for the oncology advances practice nurse 2006.; Van Gerpen, et al. Clinical Journal of Oncology Nursing 2004.; Adapted from NLB
41
Consensus Recommendations: CJON Supplement Vol 12. 2008.
TE: Prophylaxis
Mechanical
· Sequential Compression Devices
· Anti-Embolism Stockings
· Exercise Regimen
Pharmaceuticals - Therapy Dose Reductions
·
Dexamethasone
· 20 to 40 mg once weekly
· 20 to 40 mg days 1 to 4 on 28-day cycle
http://www.nhlbi.nih.gov/health/dci/Diseases/Dvt/DVT_Treatments.htm; Adapted from NLB Consensus Recommendations: CJON
42
Supplement Vol 12. 2008. Thalomid® Prescribing Information; Dexamethasone Prescribing Information
TE Prophylaxis: Pharmaceutical
Agent
Suggested Dose
Salicylic Acid (aspirin)
325 mg or 81 mg daily
Unfractionated Heparin
5000 IU sc bid
Low Molecular Weight Heparin
- enoxaparin
40 mg sc daily
- dalteparin
200 IU/kg sc daily
Fondaparinux
2.5 mg sc daily
Warfarin
Weight based
· 1 mg <70 kg
· 2 mg 70 kg
Prophylaxis tailored to individual patient's risk profile.
BaxterHealthcare, 2004.; Sanofi-aventis, 2007.; Pfizer, Inc., 2007.; GlaxoSmithKline, 2005.; Bristol-Myers Squibb, 2007.; Miller, et al. Leukemia and Lymphoma 2006.; Barlogie, et al. Blood 2005.; Bennett, et al. Blood 2006. Bennett, et al. JAMA
2007.; Celgene Corporation, 2007b.; Harousseau, et al. Blood 2006.; Hussein. Thrombosis and Haemostasis 2006.; Knight, et al. New England Journal of Medicine 2006.; Lonial, et al. From
http://www.haematologica.it/content/vol92/6_supplement_2/index.dtl 2007.; Manochakian, et al. Oncologist 2007.; Millennium Pharmaceuticals, Inc., 2007.; Offidani, et al. Blood 2005.; Ortho Biotech Products, L.P., 2007.; Palumbo, et al. Leukemia
43
2008; Richardson, et al. Journal of the National Comprehensive Cancer Network 2007.; Zangari, et al. Blood 2002.; Palumbo, et al. Leukemia (In press); Adapted from NLB Consensus Recommendations: CJON Supplement Vol 12. 2008.
Overview of Peripheral Neuropathy (PN)
Consensus Statement
· PN may be a symptom of MM
· PN may be caused by THALOMID®/VELCADE®
treatment
· PN is a challenging adverse event that may:
· Affect quality of life
· Compromise optimal treatment
· PN Management strategies include:
· Ongoing evaluation
· Dose and schedule modifications
· Pharmacologic interventions
· Non-pharmacologic approaches
· Patient education
Adapted from NLB Consensus Recommendations: CJON Supplement Vol 12. 2008.; Thalomid® Prescribing Information, Velcade® Prescribing
44
Information; Colson et al. Clinical Journal of Oncology Nursing 2004.; S. Lonial. The American Journal of Hematology/Oncology 2007.
PN: Definition, Signs, and Symptoms
PN is a change in feeling/damage to the peripheral nervous system
including injury, inflammation, or degeneration of peripheral nerve
fibers resulting in sensory and motor neuropathies.
Signs/symptoms
Severe symptoms
· Numbness
· Burning Pain
· Tingling
· Muscle Wasting
· Paresthesias
· Paralysis
· Sensitivity to Touch
· Organ Dysfunction
· Muscle Weakness
· Sensation of cold (foot)
Adapted from NLB Consensus Recommendations: CJON Supplement Vol 12. 2008.
45
http://www.ninds.nih.gov/disorders/peripheralneuropathy/detail_peripheralneuropathy.htm
PN: Neurotoxicity Assessment Tool
Instructions for Patients
Instructions for Healthcare Professionals
By circling one number per line, please indicate how true each
This assessment tool is provided to help you
statement has been for you during the past seven days, using the
evaluate peripheral neuropathy in patients receiving
following scale:
chemotherapy. Healthcare professionals may find
discussion of patients' responses helpful in
0 = not at all
determining the grade of neuropathy as defined by
1 = a little bit
the National Cancer Institute Common Terminology
2 = somewhat
Criteria for Adverse Events; however, no direct
3 = quite a bit
correlation exists between assessment scores and
4 = very much
toxicity grades.
I have numbness or tingling in my hands.
0
1
2
3
4
I have numbness or tingling in my feet.
0
1
2
3
4
I feel discomfort in my hands.
0
1
2
3
4
I feel discomfort in my feet.
0
1
2
3
4
.
I have joint pain or muscle cramps.
0
1
2
3
4
I feel weak all over.
0
1
2
3
4
I have trouble hearing.
0
1
2
3
4
I get a ringing or buzzing in my ears.
0
1
2
3
4
I have trouble buttoning buttons.
0
1
2
3
4
I have trouble feeling the shape of small objects when they are in my hands.
0
1
2
3
4
I have trouble walking.
0
1
2
3
4
Calhoun, et al. Proceedings of the American Society of Clinical Oncology 2000.; Cella, 1997;Cella, et al. Journal of Clinical
46
Oncology 1993.; http://ctep.cancer.gov
PN: Dose/Schedule Modifications
THALOMID® Therapy
Grade 1 or Mild: (mild pain not interfering with function)
· Continue therapy
Grade 2 or Moderate: (interferes with function, not ADL)
· Intermittent Continue therapy
· Continuous Stop therapy and observe whether
symptoms persist
· If symptoms resolve Restart therapy at a reduced dose
Grade 3 or Severe: (severe pain, interferes with ADL)
· Hold therapy until PN resolves to baseline
· Once symptoms resolve Restart therapy at a reduced
dose
Grade 4 or Disabling:
· Discontinue therapy permanently
Adapted from NLB Consensus Recommendations: CJON Supplement Vol 12. 2008.; Thalomid® Prescribing Information; http://ctep.cancer.gov/reporting/ctc_v30.html; Colson, et
al. Clinical Journal of Oncology Nursing 2004.; NCCN 2007.; NINDS 2007.; Tariman. Clinical Journal of Oncology Nursing 2003.; Visovsky, et al. From
47
http://www.ons.org/outcomes/volume2/peripheral/pdf/PEPCardDet-peripheral.pdf 2007.
PN: Dose/Schedule Modifications
VELCADE® (Bortezomib) Therapy
· Grade 1 or Mild:
Continue therapy
· Grade 1 w/ Pain or Grade 2:
Reduce dose to 1 mg/m2
· Grade 3 or Severe:
Hold therapy PN resolves to baseline

Restart at 0.7 mg/m2

Consider changing treatment to once weekly
· Grade 4:
Discontinue therapy
Velcade® Prescribing Information; http://ctep.cancer.gov/reporting/ctc_v30.html; Adapted from NLB Consensus Recommendations: CJON Supplement Vol 12. 2008.; ACS, 2005.;
Armstrong, et al. Oncology Nursing Forum 2005.; Colson, et al. Clinical Journal of Oncology Nursing 2004.; NCCN 2007.; NINDS, 2007.; Tariman. Clinical Journal of Oncology Nursing 2003.;
48
Visovsky et al. From http://www.ons.org/outcomes/volume2/peripheral/pdf/PEPCardDet_peripheral.pdf 2007.
General Strategic Recommendations for
PN Patient Education
· Always report symptoms early to healthcare team
Sensory Symptoms
· Tingling
· Numbness, or pain in your hands or feet
· Trouble hearing; ringing or buzzing in your ears
· Weakness all over
Motor Symptoms
· Trouble fastening buttons
· Difficulty opening jars
· Difficulty feeling the shape of small objects in your hands
· Trouble walking
· Notify if S/S worsen
· Home safety with decreased sensation in extremities
· Is driving appropriate?
· Family members to assess hot/cold temperatures if
patient is unable to do so
Adapted from NLB Consensus Recommendations: CJON Supplement Vol 12. 2008.; NCCN 2007; NINDS 2007; Tariman, Clinical Journal of Oncology Nursing 2003.;
49
Visovsky, et al. From http://www.ons.org/outcomes/volume2/peripheral/pdf/PEPCardDet_peripheral.pdf. 2007.
General Strategic Recommendations for
the Management of PN
· Non-Pharmaceutical
Massage affected areas with cocoa butter,
capsaicin cream
Home health referral to evaluate safety at home
Assistance with ADL
Referrals: pain management, neurology, physical/occupational therapy
· Supplements and Pharmaceutical
For all patients prior to therapy
· B-complex vitamins including B1, B6, B12 (at least 400 mcg)
· Folic Acid 1 mg daily
For Grades 2 or higher
· Tricyclic antidepressants
· Try amino acids on an empty stomach
(eg, acetyl-L-carnitine, L-glutamine, and alpha lipoic acid)
· Neurontin®, Lyrica®, Cymbalta®
· May apply Lidoderm® patch 5% to affected area every 12 hours
NLB Consensus Recommendations: CJON Supplement Vol 12. 2008.; NCCN 2007; NINDS, 2007; Tariman, 2003, Adapted from CJON June 2008, Colson et al., 2004, Clinical Journal of Oncology Nursing; NCCN
2007; NINDS, 2007; Tariman, 2003, Clinical Journal of Oncology Nursing; Visovsky et al., 2007, Clinical Journal of Oncology Nursing; Visovsky et al.,
2007,http://www.ons.org/outcomes/volume2/peripheral/pdf/PEPCardDet_peripheral.pdf http://www.ons.org/outcomes/volume2/peripheral/pdf/PEPCardDet_peripheral.pdf; Endo Pharmaceuticals; 2006; Lidoder 50
m®
(lidocaine patch 5%) prescribing information; http://www.mayoclinic.com/health/peripheral-neuropathy/BN00046
Overview of Gastrointestinal (GI)
Side Effects
Novel therapeutics can cause serious
GI adverse events:
· Constipation
· Diarrhea
· Nausea
· Vomiting
Adapted from NLB Consensus Recommendations: CJON Supplement Vol 12. 2008.
51
GI Side Effects Are Common AEs of
Novel Therapies
Incidence of GI AEs in MM Patients Receiving Novel Therapies
REVLIMID® a (lenalidomide)
THALOMID® a
VELCADE® (bortezomib)
(2 studies, N = 346)
(Open label study, N = 102)
(Phase 3 trial, N = 331)
Toxicity
All Grades
Grade 3b
All Grades
Grade 3b
All Grades
Grade 3b
(%)
(%)
(%)
(%)
(%)
(%)
Constipation
39
2
55
8
42
2
Diarrhea
29
2
12
1
57
7
Nausea
22
<2c
28
5
57
2
Vomiting
10
<2c
12
2
35
3
a REVLIMID® and THALOMID® administered in combination with dexamethasone.
b No Grade 4 events were reported.
c Only Grade 3 and 4 adverse events with an incidence of 2% were reported.
Thalomid® Prescribing Information, Revlimid® Prescribing Information, Velcade® Prescribing Information
52
Adapted from NLB Consensus Recommendations: CJON Supplement Vol 12. 2008.
General Management of Constipation
Non-pharmacologic
·
Increase fluid intake
·
Warm/hot drink 30 minutes before normal defecation time
·
Dietary changes ­ increase fiber
·
Provide comfort, privacy, convenience during defecation
·
Increase physical activity
Pharmacologic
·
Consider bowel regimen
·
Consider laxative and stimulant agents:
­ Magnesium sulfate 15 g PO daily
­ Magnesium citrate 200 mL PO daily
­ Lactulose 15 to 60 mL PO daily
­ Biscadoyl 5 to 20 mg PO at night or 10 to 20 mg rectally after meal
·
Assess for bowel obstruction
·
Consider for disimpaction
·
Consider intravenous hydration
Adapted from NLB Consensus Recommendations: CJON Supplement Vol 12. 2008.; ASCO's Curriculum Diarrhea 2005; Bush. Oncology Nursing
53
Forum 2004.; Engelking. Cancer Symptom Management 2004.; Mercadante. Principles & Practice of Palliative Care & Supportive Oncology 2007.
General Management of Diarrhea
Non-pharmacologic
· Increase fluid intake
· Avoid caffeinated, carbonated, or heavily sugared drinks
· Dietary changes - avoid fiber
Pharmacologic
· Caution patient concerning medications or herbal
supplements, which can cause diarrhea
· Antidiarrheal agents: Imodium®, Lomotil®, tincture of
opium, Sandostatin®
· Intravenous hydration to correct electrolyte imbalance
NLB Consensus Recommendations: CJON Supplement Vol 12. 2008. American Gastroenterological Association, 2000; American Society of Clinical Oncology,54
2005a, 2005b, 2005c; National ComprehensiveCancer Network, 2007.
General Management of Nausea
and Vomiting
Non-pharmacologic
·
Dietary intolerance and restrictions
·
Avoid exercise and do not lie flat for 2 hrs after eating
·
Fresh air and loose clothing
·
Relaxation, guided imagery, biofeedback, acupuncture
Pharmacologic
·
Select anti-emetics based on how strongly the novel agents stimulate
N/V and consider type of N/V
Nausea: Ativan®, Compazine®, Decadron®, Pepcid®, Phenergan®,
Reglan®, or Zantac®
Vomiting: Emend®, Zofran®, Kytril®, Anzemet®, or Aloxi®
·
Intravenous hydration to correct electrolyte imbalance
Adapted from NLB Consensus Recommendations: CJON Supplement Vol 12. 2008.; ASCO's Curriculum Nausea and vomiting 2005;
55
NCI Nausea and vomiting 2007
Novel Therapy Management for GI AEs
Dose Modification for Novel Therapies in Patients With GI Toxicities
Therapy
Toxicity
Recommendation
Lenalidomide
Grade 3 or 4 toxicities judged to
Hold treatment and restart at next lower
be related to lenalidomide therapy
dose level when toxicity has resolved to <
grade 2. Do not dose below 5 mg daily.
Thalidomide
Grade 3 or 4 constipation
Patients who develop side effects such as
constipation may benefit by either
temporarily discontinuing the drug or
continuing at a lower dose. With the
abatement of these side effects, the drug
may be started at a lower dose or at the
previous dose based on clinical judgment.
Bortezomib
Any grade 3 nonhematologic
Hold bortezomib until toxicity resolves, then
toxicity
reinstate therapy at a 25% reduced dose (1.3
mg/m2 dose reduced to 1 mg/m2; 1 mg/m2
dose reduced to 0.7 mg/m2).
Adapted from NLB Consensus Recommendations: CJON Supplement Vol 12. 2008.;
56
Celgene Corporation, 2007a, 2007b; Millennium Pharmaceuticals, Inc., 2007
Summary Recommendations for all
Emergent Side Effects of Novel Therapy
Effective management includes:
·
Monitoring patients carefully
·
Educating patients and caregivers about what to expect during treatment
·
Appropriate prophylaxis
·
Pharmacologic and non-pharmacologic interventions
Effective management leads to:
·
Increased adherence to therapy
·
Improved quality of life
·
Prevention of serious adverse events leading to prolonged hospitalization,
increased morbidity and mortality
Future directions:
·
New combinations
·
Targeted therapies
Adapted from NLB Consensus Recommendations. In Press, CJON June 2008; Ghobrial, et al. (2007) Oncology, 21, 785-792.
57
Lonial, S. (2007) The American Journal of Hematology/Oncology, 6, 194-196.
Educational Resources
American Cancer Society
National Cancer Institute
International Myeloma Foundation and the Multi-lingual
IMF Website www.myeloma.org
· Teleconferences and Webcasts
­
Video and audio programs on critical current myeloma
issues
· IMF Patient/Family Seminars, ONS and ASH Symposia
and Regional Community Workshops
· IMF Myeloma Today Newsletter
· Toll Free Hotline (800)452-CURE
58
Educational Resources (continued)
Publications
· IMF disseminates brochures to thousands of patients
and physicians every year to educate them on the
disease and the latest, cutting-edge myeloma research
and information.
· The brochures are distributed via IMF Info Packs in
various languages, and are sent directly to myeloma
institutions and directly to patients via IMF programs,
support groups, and by request on our Web site.
· All brochures are updated post-ASH each year, and are
reviewed by IMF Scientific Advisors. Translations are
done and approved by myeloma doctors in each
country to ensure information accuracy.
www.myeloma.org
59
CE Credit
There are no prerequisites or fees for participating in and receiving
credit for this activity. Participants must 1) study the educational
activity, 2) download the posttest from the link provided in the
confirmation email, complete the posttest by recording the best
answer to each question in the answer key on the form, 3) complete
the evaluation form, 4) mail, e-mail or fax the completed form to
Medical Education Resources at
Mail: Medical Education Resources 1500 W. Canal Court, Building B
Littleton, CO 80120-6404
Fax: 720-449-0217
E-mail: Kathryn Holland, kathryn@mer.org
A statement of credit will be issued only upon receipt of a completed
activity evaluation form and a completed posttest with a score of
70% or better. Statements of credit will be mailed within 6 weeks of
the activity.
60
Accreditation
· This continuing education activity provides a maximum of
1.0 contact hours
· Medical Education Resources is an approved provider of
continuing nursing education, by the Colorado Nurses
Association, an accredited approver by the American
Nurses Credentialing Center's Commission on
Accreditation.
Please email Diane Moran at the International Myeloma
Foundation if you have any questions
dmoran@myeloma.org
61

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