Patient Best Practices in Myelodysplastic Syndromes

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					 Patient Best Practices in
Myelodysplastic Syndromes
       Tammy De Gelder
      November 18, 2011
Objectives

•   To explore nursing issues when caring for patients
    with myelodysplastic syndrome (MDS) along with
    treatment effects

•   To understand patient and family views of MDS and
    their expectations of care

•   To appreciate the importance of relationships
    between the varied health care professionals to give
    the best possible outcomes in MDS



                                                           2
               Case Study #1
Male 71 year old retired scientist

Past Medical History
Childhood meningitis
Dental infection June 2010
New diagnosed atrial fibrillation started on
aspirin 81mg OD
                 Case Study #1
• Patient underwent dental surgery that was complicated
  by infection at the surgical site that was treated with
  Clarithromycin. Developed GI symptoms and had a CBC
  which documented neutropenia, thrombocytopenia,
  macrocytic anemia
• Patient relatively asymptomatic from his pancytopenia;
  minor weight loss associated with dental surgery now
  recovered, no other infections, hospitalizations,
  respiratory symptoms or bleeding/bruising
• He is active and likes to ballroom dance
              Case Study #1
• What would you do to confirm the diagnosis
  of MDS?
       What is MDS?
        MDS is a clonal stem cell
        disorder characterized by:
           • Hypercellular/Dysplastic bone
             marrow
           • Cytopenias
           • Abnormal Cytogenetics

                                                     Image: Malask, p; ASH Image Bank (2004);
                                                     doi:10.1182/ashimagebank-2004-101115




Miller KB. Curr Treat Options Oncol. 2000;1:63-69.                                              6
Kurzrock R. Semin Hematol. 2002;39(suppl 2):18-25.
       What are the clinical features of MDS?

       • Many patients with MDS are asymptomatic
              • In these patients, MDS is discovered during routine
                blood tests




                                                                      7
Hofmann W-K. Ann Rev Med. 2005;56:1-16.
       Patients’ symptoms reflect a range of
       cytopenias
       • Symptoms may include fatigue, infection,
         bruising, hemorrhage
       • Bone marrow failure
               • Approximately 40% of patients transform to AML




Kurzrock R. Semin Hematol. 2002;39:18-25.                         8
Greenberg P, et al. Blood. 1997;89:2079-2088.
                              Incidence rates of MDS increase with
                              age
                               40                                                        36.2   36.4
  Rate per 100,000 per year




                               35
                               30
                                                                                  25.7
                               25
                               20                                          16.6
                               15
                                                                      10
                               10
                                                               5.4
                               5                 1.5   2.8
                                     0.6   0.9
                               0
                                    40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84       >84

                                                             Age (years)


                                                                                                       9
Ma W et al. Cancer. 2007;109:1536-1542.
             Case Study #1
• CBC – WBC – 1.9 HB 102 PLT – 119 Neuts 0.2
  no blasts in peripheral blood
• Chemistry – all within normal limits
• Bone marrow aspirate – hypocellular marrow
  with 11% myleoblasts
• Cytogenetics – normal
• What IPSS classification is he? Median
  survival? 25% AML progression?
       MDS classification and prognostication

       • Classification Systems:
               • French-American-British (FAB)
               • World Health Organization (WHO)


       • Prognostic Scoring Systems:
               • International Prognostic Scoring System (IPSS)




Kurzrock R. Semin Hematol. 2002;39(supp2):18-25.
Bennett J. Int J. Hematol. 2000;72:131-133.                       11
Greenberg P et al. Blood.1997;89:2079-2088.
       FAB classification
                                     Bone marrow       Peripheral          Other cellular
                Name
                                        blasts        blood blasts            findings
                RA                             <5%          <1%                     --
                                                                              >15% ringed
                RARS                           <5%          <1%
                                                                              sideroblasts

                RAEB                        5%-20%          <5%                     --

                RAEB-T                     21%-29%          >5%                Auer rods
                                                                              Monocytosis
                CMMoL                          20%          <5%
                                                                                >109/L
                    FAB=French-American-British; RA=Refractory anemia; RARS=RA with ringed
                    sideroblasts
                    RAEB (-T)=RA with excess blasts (in transformation); CMMoL=Chronic
                    myelomonocytic leukemia


                                                                                             12
Kurzrock R. Semin Hematol. 2002;39(supp2):18-25.
       Major WHO categories

     Category                               Peripheral blood            Bone marrow
              RA without              Blasts <1%;
     1a                                                        Blasts <5%; ringed sideroblasts<15%
              dysplasia               monocytes<1000/mm3
                                      Same + dysgranulocytes
              RA with                                          Same + dysgranulocytes and/or
     1b                               and/or
              dysplasia                                        dysmegakaryocytes
                                      giant platelets

              RARS without            Blasts <1%;
     2a                                                        Blasts <5%; >15% ringed sideroblasts
              dysplasia               monocytes<1000/mm3

                                      Same + dysgranulocytes
              RARS with                                        Same + dysgranulocytes and/or
     2b                               and/or
              dysplasia                                        dysmegakaryocytes
                                      giant platelets




                                                                                                      13
Bennett J. Int J Hematol 2000;72:131-133.
         Major WHO categories (cont’d)

     Category                               Peripheral blood            Bone marrow
                                      Blasts 1%-5%;
     3a       RAEB-I                                           Blasts 5%-10%
                                      monocytes<1000/mm3
                                      Blasts 6%-20%;
     3b       RAEB-II                                          Blasts 11%–20%
                                      monocytes<1000/mm3
                                      Blasts<1%-20%;
     4        CMML                                             Blasts 0%–20%
                                      monocytes>1000/mm3




                                                                                      14
Bennett J. Int J Hematol 2000;72:131-133.
        MDS is a continuum from low- to high-
        risk to AML
                                       Bone marrow blast count scores assist in
           RA without dysplasia          patient classification as MDS or AML
           RA with dysplasia
           RARS without dysplasia
                                                                                        AML
   WHO




           RARS with dysplasia              RAEB-I                RAEB-II


                            5%                       10%                          20%   30%
  FAB




                 RA
                RARS
                                                           RAEB                    RAEB-T



                                                     MDS


Kurzrock R. Semin Hematol 2002;39(supp2):18-25.
                                                                                              15
Bennett J. Int J Hematol 2000;72:131-133.
       A disease with variable prognosis
       IPSS scoring defines risk level in MDS

                                                Standard IPSS score
          Prognostic variable                        0                    0.5   1.0      1.5       2.0

          Bone marrow blasts                       <5%                5%-10%     --    11%-20%   21%-30%

          Karyotype*                              Good           Intermediate   Poor

          Cytopenias†                              0/1                    2/3



        International Prognostic Scoring System (IPSS) scoring is based on three prognostic variables

        *Good=normal, -Y, del(5q), del(20q)
          Intermediate=other karyotypic abnormalities
          Poor=complex (>3 abnormalities) or chromosome 7 abnormalities
        † Hemoglobin<10 g/dL; ANC<1800/mL; platelets<100,000/mL


                                                                                                           16
Greenberg P et al. Blood 1997;89:2079-2088.
       A disease with variable prognosis
       Determining patient risk from the IPSS score


                                 IPSS Score     Risk grouping

                                          0         Low risk

                                     0.5–1.0   Intermediate-1 Risk

                                     1.5–2.0   Intermediate-2 Risk   Higher-risk
                                                                     MDS
                                       >2.5         High Risk




                                                                                   17
Greenberg P et al. Blood 1997;89:2079–2088.
       A disease with variable prognosis
       IPSS score linked to survival

                         6                       IPSS risk category
                         5
          Time (years)




                         4
                         3
                         2
                         1
                         0
                                   Low        Intermediate 1 Intermediate 2   High

                                      With increases in IPSS score:
                                               Survival decreases
Greenberg P et al. Blood 1997;89:2079-2088.                                          18
Balducci L. Cancer 2006;10610:2087-2094.
TREATMENT OPTIONS
WHAT ARE THEY?
                                             Treatment Options

           Curative treatment
           Allogeneic BMT only known curative modality
                  – Most patients are ineligible
                          •   40% of patients undergoing BMT are cured
                          •   30-40% transplant-related mortality rate
                          •   Significant morbidity: organ RRT, infection, GVHD
                          •   20-30% risk of relapse post-BMT
                  – Timing of BMT critical (risk/benefit consideration)



Gore S. Cancer Control 2004; 11(supp6):3-6                                    20
Alberta Cancer Board, Clinical Practice Guideline LYHE004, Nov 2007
                                            MDS treatment goals

           Non-curative Goals

                           Extend survival
                           Improve quality of life


                           Decrease risk of AML transformation
                           Decrease transfusion needs
                           Minimize infectious complications


                                                                  21
Gore S., Cancer Control, 2004; 11(s6):3-6
       Treatment options
             Treatment options for patients with MDS have included:

                          •    Transfusions
                          •    Iron chelation
                          •    Antimicrobials
                          •    Growth factors

             These options are supportive in nature and do not treat
             the underlying disease

             Hematopoietic stem cell transplantation is the only
             curative therapy for MDS. Unfortunately, this is a
             limited option as many patients are ineligible for
             transplant.
Gore S. Cancer Control. 2004;11(suppl6):3-6.                            22
Alberta Cancer Board, Clinical Practice Guideline. LYHE004, Nov 2007.
       Chemotherapy in MDS
       • Hydroxyurea can reduce blast counts and
         improve MDS/AML-related symptoms
       • Low-dose Ara-C (10 mg/m2 sc bid) only
         achieved 11% complete and 21% partial
         response, with a short median duration (5.9
         months)
       • 20 mg bid Ara-C treatment resulted in 18%
         complete remission, compared with 1% for
         hydroxyurea in the UK AML-14 study

Miller KB. Ann Hematol 1992;65:162-168.                23
Burnett AK. Cancer 2007;109:1114-1124.
                           Conventional “AML”
                       chemotherapy regimen in MDS
          • CR rates with “7+3”-type chemotherapy in MDS
            are lower than with de novo AML (~35-55%)
          • Higher treatment-related mortality rates are
            expected than with de novo AML (~20-30%)
          • Shorter CR durations result (~6 months)
          • 5-year survival < 10%
          • Better results seen in patients age < 55 and if
            normal karyotype (65% CR and 25% 5-year
            survival)

                                                          24
Verbeek W. Ann Hematol 1997;74:205
       VIDAZA

             What is Vidaza?
       it is often referred to as epigenetic therapy (something
           that changes the cell without changing the DNA)
       Vidaza works in 2 ways


                                                            Demethylating agent
                     Cytotoxic Agent                    (Takes away a methyl group
                       (kills cells)                        that is added to DNA
                                                           in MDS so the cell can
                                                             function normally)




                                                                                     25
VIDAZA® Product Monograph, 2009. Celgene Corporation.
       VIDAZA®: Indications

             VIDAZA® (azacitidine for injection) is indicated
             for the treatment of adult patients who are
             not eligible for hematopoietic stem cell
             transplantation with:

              • Intermediate 2 and High-risk Myelodysplastic
                Syndromes (MDS) according to the International
                Prognostic Scoring System (IPSS)
              • Acute Myeloid Leukemia (AML) with 20%-30% blasts
                and multi-lineage dysplasia, according to World
                Health Organization (WHO) classification
                                                                   26
VIDAZA® Product Monograph, 2009. Celgene Corporation.
       AZA-001 study design




         • Patients continued treatment until disease progression, relapse after
           response, or unacceptable toxicity
         • To optimize patient benefit, investigators aimed to treat patients
           with VIDAZA® for 7 days every 28 days and for at least 6 cycles

                                                                                   27
Fenaux P et al. Lancet Oncol 2009;10:223-232.
       AZA-001: Study endpoints
         Primary endpoint:
                                                      Secondary endpoints included:

           Overall survival
                                                                 Transfusion
                (OS)                                            independence



                                                       Time to           Number of infections
                                                  transformation to            requiring
                                                acute myeloid leukemia       intravenous
                                                         (AML)              antimicrobials




                                                                                                28
Fenaux P et al. Lancet Oncol 2009;10:223–232.
 AZA-001
 VIDAZA® extended median survival and
 nearly doubled 2-year OS in higher-risk
 MDS patients
                 VIDAZA® nearly doubled the 2-year overall survival rate




                                                                           29
Fenaux P et al. Lancet Oncol 2009;10:223–232.
 AZA-001
 VIDAZA® improved survival in patients
 with WHO AML (20%-30% blasts)
                                 Median survival in patients with WHO AML




VIDAZA® Product Monograph, 2009. Celgene Corporation.                       30
Fenaux P et al. J Clin Oncol 2010;28:562-569.
        AZA-001
        VIDAZA® reduced transfusion
        dependence in higher-risk MDS patients
                                 100%
                                                                                    P<0.0001
                                 80%
                  Patients (%)




                                 60%                      45.0%
                                                                  a




                                 40%
                                                                                b

                                 20%                                    11.4%

                                  0%
                                                        VIDAZA®       Conventional Care
                                                        (50/111)          (13/114)
                                                          Patients who were
a(95%   CI, 35.6%-54.8%)
b(95%
                                                  transfusion-dependent at baseline
        CI, 6.2%-18.7%)
                                                                                               31
Fenaux P et al. Lancet Oncol. 2009;10: 223-232.
       AZA-001
       VIDAZA® delayed progression to AML
                                        Time to AML transformation


                                                                        Conventional Care Regimen

                                                         11.5           VIDAZA®

                                                                     17.8
                                                                                    P<0.0001


                          0                     5   10          15      20

                                      Time to AML transformation (months)



                                                                                                32
Fenaux P et al. Lancet Oncol 2009;10:223-232.
       AZA-001
       VIDAZA® reduced infection risk

                                                        Infections requiring IV antibiotics

                                                                             0.92
                    Infections per patient-year




                                                  1.0

                                                  0.8
                                                                 0.60
                                                  0.6
                                                                                             P=0.0032
                                                  0.4

                                                  0.2

                                                  0.0
                                                                         Conventional Care
                                                               VIDAZA®
                                                                              Regimen

                                                                                                        33
Fenaux P et al. Lancet Oncol 2009;10:223-232.
       CALGB 9221
       A Randomized Phase III Trial of SC
       VIDAZA® in MDS
                                                                                   Continue
                         R                                                           until       A
                                       Supportive                       No         endpoint
                         A                                                                       S   Response
                                       care* alone             Exit
    Stratify:            N                                   criteria              Azacitidine   S   • Continue
                                     (observation)                      Yes
    • RA                                                                            (Dose as     E   No response
                         D
    • RARS                                                                           below)
                                                                                                 S   • Off study
                         O
    • RAEB
                         M                                                                       S
    • RAEB-T
    • CMMoL               I
                                                      Azacitidine 75 mg/m2/d SC
                          Z
                                                  X 7 days every 28 d x 4 cycles
                          E
                                     BM                          BM                     BM
                     Day              0               29         57           85       113

           *Transfusions and antibiotics used as needed; hematopoietic growth factors
             were prohibited

                                                                                                                   34
Silverman LR et al. J Clin Oncol 2002;20:2429-2440.
 CALGB 9221
 VIDAZA® provides improved quality of
 life




        Patients who crossed over from supportive care to VIDAZA®
             • Showed a significant improvement in physical quality of life
               scores, including physical function, fatigue, and dyspnea
                                                                              35
Kornblith AB et al. J Clin Oncol 2002;10:2441–2452.
Summary: Key Clinical Data
• VIDAZA nearly doubled the 2-year overall
  survival rate compared with convention care in
  patients with higher-risk MDS
• VIDAZA tripled the 2-year overall survival rate
  compared with conventional care in patients with
  (WHO) AML (20-30% blasts)
• VIDAZA reduced transfusion dependence in
  higher-risk MDS patients
• VIDAZA provides improved quality of life with
  significant improvements in physical function,
  fatigue, and dyspnea
              Case Study #1
• start vidaza therapy however very concerned
  about constipation which he has experienced
  in the past
       Dosing

       • Start all patients at 75 mg/m2 of body surface
         area, regardless of patient’s baseline
         hematology lab values




                                                          38
VIDAZA® Product Monograph, 2009. Celgene Corporation.
     VIDAZA® (azacitidine for injection): SC
     Dosing
    Preparation
    1. Single-use vial (100 mg) reconstituted
         with 4 mL of sterile water (25 mg/mL)
    2. Resulting product is a suspension;
         appearance is cloudy
    3. Reconstituted drug may be stored for
         up to 45 min at room temperature or
         8 hrs refrigerated
    4. Procedures for handling/disposing of
         anti-cancer drugs should be applied
   Administration
   1. Suspension must be re-suspended by inverting syringe
        2-3 times and rolling syringe between palms for 30 seconds
   2. Doses >4 mL should be divided into 2 syringes and
        administered into 2 different sites
Images with permission of L. Silverman, MD.
                                                                     39
VIDAZA® Product Monograph, 2009. Celgene Corporation.
How much should be in a syringe?

• No one knows and there is no nursing evidence
  to support how much drug can be injected into a
  site
• Volumes injected into a site will vary by
  institution
       Sites for Injection




 • Subcutaneous injections can be     • Injections should be given
   given in the arms, thighs, or        approximately 1 inch apart
   abdomen (careful to avoid the belt • Avoid giving injections in areas that are
   line)                                burned, reddened, inflamed, swollen,
 • Rotate sites to keep skin healthy    or damaged by prior injections


                                                                                    41
Demakos, EP et al. Clin J Oncol Nurs. 2005;9:417-423.
       Subcutaneous Injection
                                                        • A syringe with 25 gauge 5/8
                                                          inch needle is recommended
                                                          for SC injection
                                                        • Note: Changing the needle
                                                          after drawing up the
                                                          medication, will help to
                                                          reduce contamination of the
                                                          outer skin layers during
                                                          administration, decreasing
                                                          the potential for irritation at
                                                          the injection site
                                                        • Give SC injections into a tent
                                                          of skin
                                                        • Insert the needle at a 45–90
                                                          angle (depending on the
                                                          amount of fatty tissue and
                                                          turgor/elasticity of the skin)    42
Demakos, EP et al. Clin J Oncol Nurs. 2005;9:417-423.
Administering VIDAZA®


• IMPORTANT: Icing the
  site prior to or
  immediately after
  the injection is not
  recommended due to
  the potential for
  decreased absorption
  of the drug



                         43
       Best practices for avoiding injection
       site reactions
1. Once the reconstituted suspension
   is drawn into the syringe, the
   needle should be changed prior to
   injection
2. After injecting, gently press gauze
   onto the needle insertion site as the
   needle is removed, to prevent the
   skin from pulling back and to help
   seal the punctured tissue
3. Patients with low platelet counts
   should be instructed to continue
   applying pressure for 10 to 15
   minutes after injection to minimize
   bleeding into the surrounding tissue

VIDAZA® Product Monograph, 2009. Celgene Corporation.   44
Demakos, EP et al. Clin J Oncol Nurs. 2005;9:417-423.
       Effective use of VIDAZA®

       • 7 consecutive days of VIDAZA® treatment (out
         of a 28 day cycle) is the only dosing schedule
         proven to provide survival benefit

       • This dosing schedule was the regimen used in
         the key survival study, AZA-001




                                                          45
Fenaux P et al. Lancet Oncol 2009;10:223–232.
                 Case Study #1
Results of Cycle #1
Received vidaza 75mg/m2 s/c for 7 consecutive days with
Ondasetron for antiemetic.
No fevers, nausea and vomiting, bleeding or bruising, no
respiratory symptoms
Tired
Issues with constipation
Received 2 units of packed red blood cells for hemoglobin
of 84
Nadir counts : Plts 72 on Day 12
End of cycle counts : neuts 0.3; plts 242 hem 105
       Safety: VIDAZA®’s well-characterized
       side-effect profile can be managed to
       allow continuous treatment
       • During the first two cycles, VIDAZA® treatment
         may result in an initial worsening of cytopenias

       • Cytopenias improve with ongoing treatment due
         to restoration of hematological function

       • Perform complete blood counts (CBC) prior to
         each treatment cycle and as needed to monitor
         response and toxicity

                                                            47
VIDAZA® Product Monograph, 2009. Celgene Corporation.
 Safety: Most common adverse
 reactions in AZA-001 – Hematologic
  System organ class                                                Number (%) of patients
   preferred terma                                      Any grade                      Grade 3/4
                                        VIDAZA®                 Best            VIDAZA®           Best
                                        (n=175)              Supportive         (n=175)       supportive
                                                             Care Only                         care only
                                                              (n=102)                           (n=102)
 Blood and lymphatic system disorders
   Thrombocytopenia                    122 (69.7)            35 (34.3)         102 (58.3)      29 (28.4)
   Neutropenia                         115 (65.7)            29 (28.4)         107 (61.1)      22 (21.6)
   Anemia                               90 (51.4)            45 (44.1)          24 (13.7)          9 (8.8)
   Leukopenia                           32 (18.3)              2 (2.0)          26 (14.9)          1 (1.0)
   Febrile neutropenia                  24 (13.7)             10 (9.8)          22 (12.6)          7 (6.9)


     aMultiplereports of the same preferred term from a patient were only counted
     once within each treatment. System organ classes and preferred terms are based
     on coding of adverse events using MedDRA
                                                                                                             48
VIDAZA® Product Monograph, 2009. Celgene Corporation.
       Incidence of new cytopenias (all
       grades) declined after the second
       cycle in the AZA-001




                                           49
Data on file, Celgene Corporation.
Neutropenia

• Tips for avoiding infection – Good hand washing
  and stay away from sick people
• Check temperature regularly and tell patient to
  call immediately if greater than 38.3
• Tylenol and Advil mask a fever
• Give instructions how to call the health care
  team
Thrombocytopenia

• Minimize bleeding risk: avoid razors, home
  safety to avoid falls, no contact sports, maintain
  regular bowel regimen to avoid straining
• Petechiae
• Reassess anticoagulants if platelets fall below
  50 x 109/L – hold ASA, contact thrombosis
• Monitor patient’s CBC response to platelet
  transfusions
Anemia

• No iron enriched vitamins or supplements
• Monitor fatigue, shortness of breath, headache,
  palpitations
• Patients have different thresholds for
  transfusions
     Safety: Most common adverse
     reactions in AZA-001- Gastrointestinal
    System organ                                         Number (%) of patients
         class                                   Any grade                     Grade 3/4
      preferred
        terma                       VIDAZA®                 Best       VIDAZA®            Best
                                    (n=175)             supportive     (n=175)        supportive
                                                         care only                     care only
                                                          (n=102)                       (n=102)
   Gastrointestinal system disorders
    Constipation       88 (50.3)       8 (7.8)                          2 (1.1)            0
    Nausea             84 (48.0)     12 (11.8)                          3 (1.7)            0
    Vomiting           47 (26.9)       7 (6.9)                             0               0
    Abdominal
                       22 (12.6)       7 (6.9)                          7 (4.0)            0
   pain
    Dyspepsia           10 (5.7)       2 (2.0)                             0               0

     aMultiplereports of the same preferred term from a patient were only counted
     once within each treatment. System organ classes and preferred terms are based
     on coding of adverse events using MedDRA
                                                                                                   53
VIDAZA® Product Monograph, 2009. Celgene Corporation.
Other Issues to think about

• Monitor kidney function ( Vidaza and its
  metabolites are primarily excreted renally)
• Liver function
• Monitor glucose
• Neurological effects: Headaches, confusion,
  dizziness, insomnia (first 2 cycles more
  pronounced)
   Monitoring recommendations for VIDAZA®
   patients (VIDAZA® Product Monograph)
       • Check liver chemistries and serum creatinine
         prior to initiation of therapy and with each
         cycle

       • Patients should be monitored for hematologic
         response and renal toxicities, with dosage delay
         or reduction as appropriate

       • Monitor patients with renal impairment for
         toxicity since VIDAZA® and its metabolites are
         primarily excreted by the kidneys
                                                            55
VIDAZA® Product Monograph, 2009. Celgene Corporation.
WHAT SHOULD WE CHANGE FOR
CYCLE #2 IF ANYTHING?
               Case Study #1
• Cycle #2
• Same dose of Vidaza
• A bit more nauseated with Gravol however
  constipation is not an issue
• Erythema at one injection site.
• Tired
• Cycle #3 delayed due to dental work
• Received 2 units of packed red blood cells on day
  15 for hemoglobin of 86 and 1 unit for
  hemoglobin of 89 on day 24
      Injection Site reaction toto Vidaza
        Injection Site reaction Vidaza
      Injectionsite reaction to VIDAZA®
            Erythema at injection abdomen
       • Erythema at injection sites, sites, abdomen
          Erythema at injection sites, abdomen




                                          Mount Sinai Patient 2005

                                            Mount Sinai Patient 2005
                                                Mount Sinai Patient 2005
                                                                           58
Images with permission of E Demakos, RN
 Safety: Most common adverse
 reactions in AZA-001 – Injection Site
   System organ class                                            Number (%) of patients
    preferred terma                                       Any grade                        Grade 3/4
                                             VIDAZA®          Best supportive   VIDAZA®        Best supportive
                                             (n=175)             care only      (n=175)           care only
                                                                  (n=102)                          (n=102)
 General disorders and administration site conditions
   Injection site erythema                   75 (42.9)                0            0                   0
   Injection site reaction                   51 (29.1)                0          1 (0.6)               0
  Injection site pain                        33 (18.9)                0            0                   0
  Injection site
                                              11 (6.3)                0            0                   0
 hematoma
   Injection site rash                        10 (5.7)                0            0                   0
   Injection site
                                                9 (5.1)               0            0                   0
 induration
  Injection site bruising                       9 (5.1)               0            0                   0
 aMultiplereports of the same preferred term from a patient were only counted once within
 each treatment. System organ classes and preferred terms are based on coding of adverse
 events using MedDRA
                                                                                                            59
VIDAZA® Product Monograph, 2009. Celgene Corporation.
              Case Study #1
Counts after cycle #2
• WBC 3.2
• Hemoglobin 104
• Plts 481
• Neuts 1.3
              Case Study #1
• Currently on cycle #13
• Feels extremely well with only some mild
  constipation on the weeks he is taking Vidaza
• WBC 5.8; Hem 124 (no transfusions needed
  since Nov 2010) Plts 415 Neuts 3.4
       Effective use of VIDAZA® (cont’d)

       • Treatment with VIDAZA® should be continued as
         long as the patient continues to benefit or until
         disease progression

       • It is recommended that patients be treated for
         a minimum of 6 cycles




                                                             62
VIDAZA® Product Monograph, 2009. Celgene Corporation.
              Case Study #1
Issues:
• Does not want to be tied down to vidaza. Can
   he stop?
• All his family is in Europe and he is alone in
   Canada
Patient Perspective

• What is myleodysplastic syndrome and how do you spell
  that?
• I heard about a person who had a bone marrow
  transplant, why can’t I have one?
• Why is she getting treatment and I’m not?
• I’m tired
• My wife is ill, I can’t go to the hospital everyday to have
  treatment
• Who is going to drive me to all my appointments?
• I want to go on vacation for a month
Patient Expectations

• A knowledgeable doctor who will give them the
  best treatment
• A health care team that will listen
• Consistent health care advice
• Safe care and treatment
• Reasonable wait times
Patient Perspective

• Explain what MDS is at their level of understanding
• Realize that you will have to explain things over and over
• Encourage patients to bring someone to their
  appointment
• Write questions down, journal
• Teach them what blood counts mean if appropriate
• Give them as many resources as appropriate
• Send them to a support group
Patient perspective on Treatment

• Realization that only a transplant is a cure
• Treatments available prolong life, they are not a
  cure
• Aware of side effects and how to manage them
• 24 hour contact, when to call
• Quality of Life
Other issues

• Rides to appointments
• Dealing with fatigue/weakness
• Caregiver issues – ill family member in home,
  primary caregiver for grandchildren
• Weather conditions
• Live on their own
• Coping with a terminal illness
                 Case # 2
• 51 year old male
• History of Coronary artery disease –
  angioplasty X3
• On Plavix 75mg, Aspirin 81mg, Crestor 20mg,
  Nexium 40mg, Domperidone 10mg QID
• While being followed by cardiologist he
  developed SOB and fatigue, blood work
  showed evidence of anemia
                   Case 2
• WBC 2.5, HB 109, plts 187, Neuts 0.9
• Bone marrow results – 3% blasts,
  normocellular
• Cytogenetics – deletion of long arm of 17.
                   Case 2
• What is his IPSS score?
• What are his treatment options
               Iron Overload
• Between 200-250mg of iron in each unit of
  blood
• Accumulates in the liver, heart, skin and
  endocrine glands, bone marrow
• Results in Cirrhosis of the liver; diabetes due
  to pancreatic islet cell failure, cardiomyopathy,
  arthritis (deposits in the joints), testicular
  failure, discolouration of the skin
         Iron Chelation Therapy
• Desferal (deferoxamine)
• Side Effects: bloody urine, blurred vision, rash,
  hives, itching, vomiting, diarrhea, stomach or
  leg cramps, fever, rapid heart beat, dizziness.
• Long term Side Effects: kidney, liver damage,
  hearing loss, cataracts
        Iron Chelation Therapy
• Exjade (deferasirox)
• Side Effects: diarrhea, nausea, vomiting,
  headache, abdominal pain, rash, fever, cough,
  mild nonprogressive increases in serum
  creatinine
• Long Term Side Effects : Kidney or liver
  damage, hearing loss, cataracts
                    Case # 3
• 68 year old female was diagnosed after having
  regular blood work for chronic fatigue
• CBC – HB :111 (recently transfused), Plts: 157,
  neuts 2.5
• Bone Marrow – 5-6% blasts with ringed
  sideroblasts.
• Cytogenetic- 5Q-
• Is transfusion dependent and has had
  approximately 20 units of PBRC over the last year.
Revlimid

• It is an immunomodulatory agent (affects your
  immune system)
• Kills off the cells with the 5q abnormality and
  replaces it with normal cells
• Directly stimulates the production of red blood
  cells by the bone marrow
Why REVLIMID in MDS

• Only useful in patients with low or INT-1 and 5q
  deletion (small subset of the MDS population 20-
  30%)
• Highly effective: 76% needed fewer transfusions
  with 67% becoming transfusion-independent
• Response time rapid Median 4.6 weeks
• Durable response – 62% who had response to
  treatment remained transfusion-free for at least
  1 year
• Less transfusions might equal improved survival
                          Patients achieving cytogenetic response
                         with lenalidomide show improved survival




                                                                    78
List, AF., Clin Adv in Hem and Onc, 2007 Vol 5(7)s10
Revlimid

• Oral agent
• Starting dose10 mg a day
• Capsules can not be broken or chewed
• Swallow whole, preferable with water, with or
  without food
• Missed dose >12 hours should be skipped
• Females who could become pregnant or plan to
  become pregnant should handle the drug with
  gloves
• Check drug interactions
Side Effects of Revlimid in MDS

• Skin rash is common and usually resolved within
  2-3 weeks. No interruption of treatment required
  unless severe
• GI – Diarrhea (especially if on an iron chelator);
  Nausea
• Cytopenias
• Febrile Neutropenia
• Rarely – Hypersensitivity pneumonitis-like
  syndrome – watch for SOB on exertion; crackles
  on physical exam
                     Lenalidomide studies: Treatment-
                          related adverse events

                                            MDS-002       MDS-003
              Adverse events  Grade 3    non-del 5q, %   del 5q, %
              Thrombocytopenia                 20             44
              Neutropenia                      25             55
              Pruritus                         1              3
              Rash                             4              6
              Diarrhea                         1              3
              Fatigue                          4              3


                                           MDS-002, n     MDS-003, n
              Deaths on study                 21             11
                  Possibly drug related        2              3


Raza et al. Blood 2008;111:86-93.                                      81
List et al. NEJM 2006;355:1456.
Concluding Remarks and Questions
The Health Care Team – Together we
create the best outcomes….
                                    Physicians
                     Laboratory                        Nursing


            Clerks                                               Pharmacy




                                    PATIENT
   Environmental Aids                                              Social work




            CCAC                                                  OT/PT


                 Spiritual Care                    Supportive Care
                                  Administration

				
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