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  • The early stages of multiple myeloma are often asymptomatic and the disease may be discovered on routine laboratory testing
    When myeloma is suspected (ie, older patients with unexplained pain, fracture, anemia), the diagnostic evaluation should include:
    Laboratory tests of both serum and urine
    Radiographic imaging
    Bone marrow biopsy
    The alterations associated with myeloma are listed here
    Quantitative immunoglobulins measure the antibodies IgG, IgA, IgM, IgE, and IgD with normal ranges: (IgG 650-1500 mg/dL; IgA (76-390 mg/dL; IgM 40-345 mg/dL; IgE 0-380 IU/ml)
    Beta 2 microglobulin is a standard measure of tumor burden for myeloma (normal range, 2.0–2.5 µg/mL)
    C-reactive protein is a surrogate marker for IL-6, a growth factor for myeloma cells
    A 24-hour urine protein electrophoresis (UPEP) measures the presence and amount of myeloma protein in the urine
    A serum-based assay (Freelite™) detects and quantifies free light chains, which may help predict the risk of progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma. This test is also easier for patients to complete than a 24-hour urine collection.
    Emerging evidence suggests that use of magnetic resonance imaging (MRI) is more sensitive and specific than x-ray and scintigraphy for detecting bone metastases in multiple myeloma patients. Thus, MRI may also be used for initial assessment of multiple myeloma.
    Abella HA. MR tops x-ray and scintigraphy for detecting bone mets. Oncology News International. 2007;16(12):27.
    Barlogie B, Shaughnessy J, Epstein J, et al. Plasma cell myeloma. In: Lichtman MA, Beutler E, Kipps TJ, Seligsohn U, Kaushansky K, Prchal JT, eds. Williams Hematology. 7th ed. New York, NY: McGraw-Hill; 2006:1501-1533.
    Durie BGM, Kyle RA, Belch A, et al. Myeloma management guidelines: a consensus report from the Scientific Advisors of the International Myeloma Foundation Hematol J. 2003;4:379-398. [erratum Hematol J. 2004;5:285].
    Multiple Myeloma Research Foundation (MMRF). Multiple Myeloma: Disease Overview. Norwalk, CT: Multiple Myeloma Research Foundation; 2006. Available at: Accessed January 8, 2008.
    Rajkumar SV, Kyle RA, Therneau TM, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005;106(3):812-817.
    Weininger M, Lauterbach B, Knop S, et al. Whole-body MRI of multiple myeloma: comparison of different MRI sequences in assessment of different growth patterns. Eur J Radiol. December 2007 [Epub ahead of print; Doi: 10.1016/j.ejrad.2007.10.025].
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    Slide 20. Durie-Salmon Staging System for MM
    The Durie-Salmon staging system has been in use since 1975. In this system, the clinical stage of disease (stage I, II, or III) is based on several measurements, including levels of M protein, the number of bone lesions, hemoglobin values, and serum calcium levels. Stages are further divided according to kidney function as determined by serum creatinine levels (classified as A or B)
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    Slide 21. International Staging System for MM
    The new International Staging System for MM is presented here. This staging system is the result of detailed statistical analysis of over 11,000 MM patients from around the world treated with standard or high-dose therapy. The system is very simple to use and worked well for all patient subgroups. It is proposed for widespread use, particularly in the clinical trial setting, and is based on measurement of serum 2 microglobulin and serum albumin, both of which are increased in cases of MM
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    Multiple myeloma is an incurable, painful, debilating disease.
    While multiple myeloma does respond to treatment with chemotherapy and radiotherapy (chemotherapy with oral melphalan and prednisone response rates = 50% to 70%), long-term complete responses are rare. The median survival with standard therapy is 3 years.
    While new treatment options, including combination chemotherapy, IFN-α, and SCT are being studied in multiple myeloma, their benefits have not been proven.
    Options are also limited for treatment of relapsed multiple myeloma. No standard therapy has been codified, and existing options are inadequate.
    In sum, new treatment options are needed for the treatment of this difficult-to-manage disease.
    National Comprehensive Cancer Network (NCCN). Practice guidelines in oncology—v.1.2001: multiple myeloma. Rockledge, PA: National Comprehensive Cancer Network; 2001.
    Rajkumar SV, Gertz MA, Kyle RA, et al. Current therapy for multiple myeloma. Mayo Clin Proc. 2002;77:813-822.
  • For VISTA
    EBMT* Response Criteria
    *European Group for Blood and Marrow Transplant
    Paraprotein: CR=100% reduction in serum & urine; nCR=100% disappearance in serum & urine; PR=≥50% reduction in serum & ≥90% reduction in urine (or absolute value <200 mg/24hrs)
    Immunofixation CR= Negative; nCR= Positive; PR= Not required
    Bone Marrow: CR=<5% plasma cells; nCR=5% plasma cells; PR=5% plasma cells
    Bone DiseaseCR= Stable or improvednCR= Stable or improved; PR= Stable or improved
    Plasmacytomas: CR= No plasmacytomas; nCR= No plasmacytomas; PR= Decreased by ≥50%
    Bladé et al. Br J Haematol 1998;102:1115-23
  • CR, complete response; HR, hazard ratio; mos, months; MP, melphalan/prednisone; OS, overall survival; Pts, patients; VISTA, Velcade as Initial Standard Therapy in Multiple Myeloma: Assessment With Melphalan and Prednisone; VMP, Bortezomib/melphalan/prednisone; yr, year.
  • According to: Mateous et al. (Haematologica 2008; 93(4), 560-565)
    VMP is highly active and well tolerated in elderly patients with newly diagnosed multiple myeloma,
    with 85% of patients alive at 3 years. Moreover, VMP may overcome the poor prognostic
    impact of various factors, particularly cytogenetic abnormalities.
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    Conclusion that new combinations of novel and emerging therapies offer personalized targeted therapy and hope, however will also require careful monitoring and effective management of emergent side effects
  • Incidence of all grades reported.
  • Incidence of all grades reported.
  • For fluid intake i.e. water, Ricelyte, Pedialyte, sports drinks, diluted fruit juices and broth.
    Loperamide (Imodium) 4 mg followed by 2 mg every 4 hours or after each unformed stool (maximum 16mg/day). May take 4 mg every 4 hours at night to allow sleep).
    atropine-diphenoxylate (Lomotil) 1 to 2 tablets every 6-8 hours
    Tincture of opium 0.6 ml PO every 4 – 6 hours
    sandostatin (Octreotide) 100 - 150 ug s.c., TID
  • MOA: Steroids appear to cause apoptosis, thus can trigger the destruction of myeloma cells
    Steroids have the following advantages:
    Shrink plasmacytomas through apoptosis
    Reduce neurological pressure
    Reduce hypercalcemia
    Achieve overall control of the disease
    Dexamethasone and Prednisone are two commonly used steroids for Multiple Myeloma
    In patients with renal failure, they can be used without dose adjustment.
    In patients who have low blood counts, they can be used without fear of further reduction in counts.
  • Concluding slide on general recommendations for side effect management of all 5 emergent side effects
    Myelosuppression, DVT/PE, Peripheral neuropathy, GI and steroid
  • E.
    A- Bortezomib is very effective but has led to pain and decreased sensation. Also a common side effect is low platelets that may occur around day 11 of treatment . Deconditioning will lead to weakness and falling down
    B. Pnuemonia is the #1 cause of death in mm patients, r/t hypogammaglobulinemia and also due to immobility. And sitting in a chair (decreased lung expansion, inspiration)
    C. Inappropriate Pain management can lead to depressed state.
    D. We must hold Bortezomib d/t neuropathy and dose reduce when it improves. Long term the PN may make her difficult to treat and is reversible only if we are careful!
  • J.J is a 76 year-old diagnosed in 2001 with IgG Kappa Myeloma. He has received 3 prior therapies that include Thalidomide, Bortezomib and now Lenalidomide.
    While gardening he experiences “10/10” pain in his back. He goes to see the NP; x rays reveal a fracture of his L2 vertebrae.
    Balloon kyphoplasty is recommended. Declines
    He receives a prescription for pain medication
  • Answer: D.
    Pain is an issue and his functional mobility will be decreased. As nurses we can expect that he will need to have good pain control to decrease these risk factors for DVT and pneumonia. Balloon kyphoplasty should be considered to correct the kyphotic deformity and improve quality of life.
  • Common clinical features of symptomatic multiple myeloma (MM) include kidney dysfunction, bone pain, fatigue, recurrent infections, anemia and hypercalcemia, yet not all features will be exhibited by all patients. [1] There are several types of renal failure that patients with myeloma may experience. Acute renal injury may exist when a patient’s serum creatinine level is greater than 2.0 gm/dL or 0.5 gm/dL from baseline. Renal failure is defined as serum creatinine levels of greater that 3.0g/dL (National Kidney Disease Foundation Guidelines, 2007). With a median age of diagnosis of 62 years in the United States, at least 25%-50% of patients will present with renal insufficiency or renal failure at diagnosis or throughout their disease, which in turn may negatively effect survival if not reversed[2]. In addition, chronic insults to the kidneys from other illnesses, treatments or the myeloma itself may further negatively impact renal function. Costs associated with patients who are requiring dialysis in the United States are difficult to quantify. However, dialysis in patients with myeloma will likely result in the risk of further complications, such as infections, and decreased quality of life.
    [1] Rajkumar SV , Kyle RA. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc. 2005;
    [2] Joan Bladé, MD; Patricia Fernández-Llama, MD; Francesc Bosch, MD; Jesus Montolíu, MD; Xosé M. Lens, MD; Silvia Montoto, MD; Aleix Cases, MD; Alex Darnell, MD; Ciril Rozman, MD; Emilio Montserrat, MD. Renal Failure in Multiple Myeloma. Arch Intern Med. 1998;158:1889-1893
  • Renal excretion may be tricky
    Bort and dex seems good
    Also FDA approved
    May not qualify due to elevated serum creatinine
    Comment : would restage with cytogenetics or FISH to assess risk, high risk disease although with prior tandem transplants we wouldn’t transplant her anyway and currently no therapies exist that would allow us to select one regimen over the other
  • Mr. D. is accompanying his wife to a visit three months after her stem cell transplant. He uncomfortably asks you if he and his wife will ever be able to have sex again. Mrs. D says that she feels no desire and that when they tried to have sex three weeks ago, she did not feel stimulated and found it to be painful. Their relationship has been strained for the last 3 years she has had myeloma.
    How would you approach this?
  • A Provider biases. As service providers, we bring our own entrenched attitudes, biases, and perceptions to our interactions with clients, and these attitudes can negatively affect our ability to provide adequate services. Some of us may feel conflict between our duties to assist our clients to achieve sexual and reproductive health and our own morals, beliefs, and values. In order to provide good services, it is critical that we separate our own attitudes about sexuality and sexual practices from our knowledge of the potential health consequences of those practices. We must help our clients to achieve healthy sexuality without imposing value judgments on their behaviors.
    B Fear of offending clients. Providers often feel that clients will not want to talk about their sex lives, or that they will offend clients by doing so. However, many providers who b have done so have found that clients are actually relieved to finally have someone to talk to confidentially—someone who can provide accurate information and help them with their concerns.
    C Lack of provider knowledge and comfort. Providers are often just as uncomfortable talking about sex as are clients, or even more so. Providers may lack knowledge about sexuality, or they may not have come to terms with their own feelings and experience related to sexuality. Providers may feel unable to handle more-complex issues that could arise during such discussion, such as sexual abuse, conflicts about sexual orientation, or sexual dysfunction, and they may lack referral resources for such problems. Training to develop knowledge, comfort, and skills, as well as development of referral resources where possible, is an important support to service provision.
    Time limitations. Health care providers may have limited time to spend with clients because of heavy client loads or limitations imposed by management. In these cases, providers can feel torn between a desire to give clients comprehensive health care and the need to deal with only the most urgent physical complaints in the short time allocated. In these situations, providers may neglect considerations of clients’ emotional and situational needs (including issues surrounding sexuality) in favor of perceived medical demands. Some of these time limitations, however, can be mitigated through changing the approach to health services. (For example, by gaining a better knowledge of a client’s circumstances, the provider can offer information that is less comprehensive and more tailored to the client’s individual situation.)
    D is correct.
    Opening communication, validating feelings and if necessary then referring to the appropriate counselor or specialist is most appropriate.
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  • A Nurse Centric Model has been developed by ScienceFirst. The premise of this model recognizes that nurses are central to patients’ management and healthcare resource coordination. This model differs from others in the literature by focusing on the perspective of the nurse and their network of inter-related, interdisciplinary patient activities. The Nurse Centric Model places the nurses’ perspective in a central role to advocate nurse leadership and to advance patient care.

    1. 1. 1 Leading the Way: Managing Multiple Myeloma for the Long -Term Accredited by Medical Education Resources Supported by The International Myeloma Foundation Grant Funding Provided by Celgene Corporation and Millennium – The Takeda Oncology Company
    2. 2. 2 Welcome and Introductions Beth Faiman, MSN, APRN-BC, AOCN Cleveland Clinic Taussig Cancer Institute Cleveland, OH
    3. 3. 3 ONS Disclaimer Meeting space has been assigned to provide a satellite symposium supported by the International Myeloma Foundation via an unrestricted educational grant during the Oncology Nursing Society’s (ONS) 34th Annual Congress, April 30 to May 3, 2009, in San Antonio, TX. The Oncology Nursing Society’s assignment of meeting space does not imply product endorsement, nor does the Oncology Nursing Society assume any responsibility for the educational content of the symposium.
    4. 4. 4 Symposium Accreditation • This continuing education activity provides 2.0 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 complete the CE Certificate Registration and Program Evaluation Form found in your guidebook and return it to the registration desk.
    5. 5. 5 Additional Accreditation Additional 3.8 CEU accreditation opportunity – Clinical Journal of Oncology Nursing (CJON) June 2008 supplement publication of the International Myeloma Foundation’s (IMF) Nurse Leadership Board (NLB) ‘Consensus Statements’ located at your table
    6. 6. 6 Faculty Chair: Beth Faiman, MSN, APRN-BC, AOCN Cleveland Clinic Taussig Cancer Institute Cleveland, OH Faculty: Joseph D. Tariman, PhC, MN, APRN-BC, OCN University of Washington Seattle, WA Sandra Rome, RN, MN, AOCN Cedars-Sinai Medical Center Los Angeles, CA Tiffany Richards, MS, ANP, AOCNP MD Anderson Cancer Center Houston, TX
    7. 7. 7 Time Discussion Topic Presenter 12:15 pm - 12:30 pm Welcome and Multiple Myeloma Overview Beth Faiman 12:30 pm - 1:00 pm Update on Novel Therapies Joseph Tariman 1:00 pm - 1:20 pm Management and Treatment of Long-Term Effects on Multiple Myeloma (Case Studies) Beth Faiman 1:20 pm - 1:40 pm Understanding and Optimizing Survivorship Care Tiffany Richards 1:40 pm - 2:00 pm Focus on the Future and Importance of Health Maintenance Sandra Rome 2:00 pm - 2:05 pm Closing Remarks Beth Faiman 2:05 pm - 2:15 pm Question & Answer Session Panel Agenda
    8. 8. 8 Learning Objectives • Describe updated data on novel agents used in the management of patients with multiple myeloma (MM) • Discuss critical issues in nursing management and medical implications of major side effect management with novel therapies in MM. • Understand the value of Survivorship Care planning, education and care. • Describe known and potential late side effects of MM and its treatment. • Identify ways to improve quality of care.
    9. 9. 9 Multiple Myeloma: A Current Perspective • Etiology of multiple myeloma (MM). • Epidemiology of MM. • Current and novel therapies in the management of MM.
    10. 10. 10San Miguel JF, et al. Pathogenesis of Multiple Myeloma: Rationale for New and Novel Therapies. Clinical Care Options: What Is Multiple Myeloma? • Cancer of plasma cells. • Healthy plasma cells produce antibodies or immunoglobulins. – Part of our humoral immunity, they are released in response to foreign body invasion. • Myeloma cells produce abnormal immunoglobulin. – Overproduce monoclonal protein or paraprotein. – Ineffective immunoglobulins. – Leads to decreased bone marrow function. – Destruction of bone tissue.
    11. 11. 11 Myeloma Cells Are Distinguished From Normal Plasma Cells by the Presence of Large Nuclei That Are Often Eccentric Vescio R. Multiple Myeloma & Amyloidosis Program,Jonsson Comprehensive Cancer Center/Cedars–Sinai Medical Center, 2005.
    12. 12. 12 Multiple Myeloma: Abnormal Proliferation of Malignant Plasma Cells Kyle and Rajkumar, N Engl J Med 2004;351:1860-1873
    13. 13. 13 Multiple Myeloma: Epidemiology • Second most common hematological malignancy. • Incidence and rates: – 1% of all cancers – US incidence: 19,900 new cases per year – US prevalence: 100,000 patients – Deaths: estimated 10,790 per year • More than 80% of affected patients >age 60. • Affects slightly more men than women (1.6:1). Merck Manual Professional. 2005; George ED, et al. Am Fam Phys. 1999;59(7):1401-1405.
    14. 14. 14 Clinical Manifestations of Multiple Myeloma • Overproliferation of plasma cells can cause: – Risk of infection – Osteolytic bone lesions – Hypercalcemia – Bone marrow suppression (pancytopenia) – Renal complication risk • Production of monoclonal M proteins causes: – Decreased levels of normal immunoglobulins – Hyperviscosity
    15. 15. 15 Major Symptoms at Diagnosis • Bone pain - 58% • Fatigue - 32% • Weight loss - 24% • Paresthesias - 5% • Asymptomatic - 11% Kyle RA. Mayo Clin Proc 2003;78:21
    16. 16. 16 Common Sites for Bone Involvement • Skull • Spine – Thoracic – Lumbar – Vertebrae • Pelvis • Long bones • Spinal cord – compression can occur
    17. 17. 17 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 for the International Myeloma Working Group. Leukemia. 2006:1-7. *Monoclonal M spike on electrophoresis IgG >3.5 g/dL, IgA >2 g/dL, light chain >1 g/dL in 24-hour urine sample.
    18. 18. 18 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 immunoglobulins ↑ M protein in serum, may have ↓ levels of normal antibodies Immunofixation Identifies light/heavy chain types M protein β2-microglobulin ↑ Levels (measure of tumor burden) 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 Evaluation of involvement of disease Alb = albumin; CBC = complete blood count; Creat = creatinine; Hgb = hemoglobin; MRI = magnetic resonance imaging; WBC = white blood cell. Abella. Oncology News International. 2007;16:27; Barlogie et al. In: Williams Hematology. 7th ed. 2006:1501; Durie et al. Hematol J. 2003;4:379; MMRF. Multiple Myeloma: Disease Overview. 2006.; Rajkumar et al. Blood. 2005;106(3):812.
    19. 19. 19 Durie-Salmon Staging System for Multiple Myeloma Durie and Salmon, Cancer 1975;36(9):842-854 Subclassification criteria: A Normal renal function (serum creatinine level <2.0 mg/dL) B Abnormal renal function (serum creatinine level ≥2.0 mg/dL) Stage Criteria Myeloma cell mass (× 1012 cells/m2 ) I All of the following: 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 <0.6 (low) II Not fitting stage I or III 0.6 - 1.2 (intermediate) III One or more of the following: 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 >1.2 (high)
    20. 20. 20 β2M=serum β2 microglobulin in mg/dL; ALB=serum albumin in g/dL International Staging System for Symptomatic Multiple Myeloma Greipp PR, et al. Blood 2005; 102: 190a STAGE VALUES Stage 1 ß2M <3.5 mg/dL ALB ≥3.5 g/dL Stage 2 Not Stage 1 or 3 Stage 3 ß2M >5.5 mg/dL
    21. 21. 21 Challenges in MM Management • Currently incurable in most patients. • Long-term complete responses are rare. • Median survival with standard therapy is about 3 years. • Autologous stem cell transplant may prolong progression free survival, but it’s not curative. • Treatment of relapse: – No standard therapy. – Existing options inadequate. New treatment options needed. NCCN Practice Guidelines; Rajkumar et al. Mayo Clin Proc. 2002;77:813-822.
    22. 22. 22 MM Treatment Options • Conventional chemotherapy: – Melphalan – Doxorubicin – Cyclophosphamide • Radiation therapy • Stem cell transplantation: – Autologous – Allogenic • Novel therapeutics: – Thalidomide – Lenalidomide – Bortezomib Thalomid® Prescribing Information, Revlimid® Prescribing Information; Velcade® Prescribing Information • Steroid therapy: – Dexamethasone – Prednisone
    23. 23. 23 Update on Novel Therapies Joseph Tariman, PhC, MN, APRN-BC, OCN University of Washington Seattle, WA
    24. 24. 24 NCCN Review Categories Transplant NCCN Category Non Transplant NCCN Category Dexamethasone 2A Bortezomib/Melphalan/Prednisone (VMP)* 1 L-Doxorubicin/Vincristine/ Dexamethasone (DVD) 2A Melphalan/Prednisone/Thalidomide (MPT) 1 Thalidomide/Dexamethasone 2A Vincristine/Doxorubicin/Dexamethasone (VAD) 2A Bortezomib/Dexamethasone 2B Dexamethasone 2A Bortezomib/Thalidomide/ Dexamethasone (VTD) 2B Melphalan/Prednisone (MP) 2A Lenalidomide/Dexamethasone 2B Thalidomide/Dexamethasone 2A Bortezomib/Doxorubicin/ Dexamethasone 2B Lenalidomide/low Dexamethasone* 2B Bortezomib/Lenalidomide/ Dexamethasone (VRD)* 2B L-Doxorubicin/Vincristine/Dexamethasone (DVD) 2B *Combinations recently reviewed by NCCN NCCN Clinical Practice Guidelines in Oncology, v2 2009 NCCN Categories of Evidence and Consensus: 1 High-level evidence, uniform consensus 2A Lower-level evidence, uniform consensus 2B Lower-level evidence, non-uniform consensus Generic Name Trade Name Bortezomib Velcade Lenalidomide Revlimid Thalidomide Thalomid
    25. 25. 25 Recent and Ongoing Clinical Studies • Transplant-eligible patients – Bortezomib/Thalidomide/Dexamethasone (VTD) vs Thalidomide/Dexamethasone (TD) – Bortezomib/dexamethasone – Lenalidomide/low-dose Dexamethasone (Rd) • Transplant-ineligible patients – VISTA: Bortezomib/Melphalan/Prednisone (VMP) vs Melphalan/Prednisone (MP) – Lenalidomide/low-dose Dexamethasone (Rd) • New combinations and early studies – Transplant-eligible patients • Bortezomib/Lenalidomide/Dexamethasone • Bortezomib/Lenalidomide/Dexamethasone vs Bortezomib/Dexamethasone – Transplant-ineligible patients • MTP vs MPR (Phase III) • VMP vs Bortezomib/Thalidomide/Prednisone (VTP) (Phase III) – Early studies • Bortezomib/Vorinostat (Phase I)
    26. 26. 26 VTD vs. TD in Patients Who Are Transplant Eligible • Study objective – VTD vs TD in preparation for autologous stem cell transplantation (ASCT) • Study design – Randomized trial – Three cycles of induction therapy • Methods – Pts. randomized to either VDT (n=199) or TD (n=200). – Stem cells were collected. – Consolidation therapy with same treatment to pts. – Results drawn from a final analysis of 399 patients. Phase III Bortezomib-Thalidomide-Dexamethasone (VTD) vs Thalidomide-Dexamethasone (TD) Prior to Stem Cell Transplantation (SCT)) Cavo et al. Blood 2008 112: Abstract 158
    27. 27. 27 • Prophylaxis – Acyclovir prophylaxis against reactivation of VZV. – TEE prophylaxis with low molecular weight heparin, aspirin, or warfarin; fixed low-dose warfarin is effective. • Conclusions: – In comparison with TD, 3 21-d cycles of VTD as primary therapy significantly increased CR+nCR rates. – These response rates translated into significantly higher CR+nCR after first ASCT in the VTD arm. – Combinations of novel induction agents, such as VTD, can have a remarkable impact on both pre- and post- ASCT clinical outcome. Conclusions From VTD vs. TD Cavo et al. Blood 2008 112: Abstract 158
    28. 28. 28 Bortezomib and Dexamethasone Prior to ASCT in Transplant-Eligible Patients • Phase III, active control, multicenter, open label, randomized – Objective: compare the CR rate with vincristine/adriamycin/dexamethasone (VAD) and bortezomib/dexamethasone combinations as induction therapy. • Number of severe AE was similar between the arms: Harousseau et al, Blood 2007 110: Abstract 450. Post Induction Post ASCT CR/nCR ≥VGPR ≥PR CR/nCR ≥VGPR ≥PR VAD 9% 24% 71% 28% 50% 88% Bortezomib/ Dexamethasone 22% 50% 89% 38% 66% 87% P-value 0.0085 0.0001 NS 0.127 0.021 NS
    29. 29. 29 • Post-induction complete remission (CR) was increased by VD compared to VAD. • One-year PFS and OS rates were 93% and 97% with VD and 90% and 95% with VAD, respectively. Conclusions From Bortezomib and Dexamethasone Prior to ASCT Harousseau et al, Blood 2007 110: Abstract 450.
    30. 30. 30 VISTA Trial: VMP vs MP in Transplant-Ineligible Patients • Study objective: – Define the differences in efficacy and outcome between VMP vs MP • Study design and method: – VMP arm (IV Bortezomib in combination with oral prednisone and oral melphalan) vs MP arm (oral melphalan and prednisone) • Primary endpoint: – Time to progression (TTP) • Secondary endpoints: – Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), time to progression (TTP) and duration of response (DOR), andsafety A Phase 3 Study Comparing Bortezomib/Melphalan/Prednisone (VMP) With Melphalan/Prednisone (MP) San Miguel et al Blood 2007 110: Abstract 76; San Miguel et al Blood 2008 112: Abstract 650; Harousseau et al Blood 2008 112: Abstract 650 Mateous et al. Haematologica 2008; 93(4), 560-565
    31. 31. 31Mateos, et al. Haematologica 2008; 93(4) 560-565 VISTA Trial: VMP vs. MP Most Common Adverse Events (in ≥30% Patients) receiving VMP (n=60) Adverse Event % Toxicities All Grades % Toxicities Grades 3/4 Anemia 86 10 Thrombocytopenia 93 51 Infection 75 16 Neutropenia 85 43 Asthenia 63 5 Nausea 55 2 Diarrhea 55 16 Peripheral Neuropathy 55 17 Constipation 52 8 Anorexia 38 2 Vomiting 30 2
    32. 32. 32 VISTA: Updated Results San Miguel JF, et al. Blood 2008 112: Abstract 650. • VMP associated with ~36% reduced risk of death. • 43% of pts in the MP arm who had subsequent therapy received Bortezomib upon disease progression. • Pts who received >4 cycles of Bortezomib: – 1- and 2-yr OS: 98.5% and 89%, respectively Months Ptsw/oEvent(%) 0 10 20 30 40 50 60 70 80 90 100 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 Median follow-up: 25.9 mos VMP: median OS not reached (75 deaths); 3-yr OS rate: 72% MP: median OS not reached (111 deaths); 3-yr OS rate: 59% HR = 0.644; P = .0032 VMP MP OS
    33. 33. 33 Conclusions • Adverse events –46% with VMP –36% with MP • Patients remained on therapy longer with VMP: –46 weeks with VMP –39 weeks with MP • Patients had a longer time to next therapy. • Patients also had longer treatment-free survival. San Miguel et al Blood 2007 110: Abstract 76; San Miguel et al. Blood 2008 112: Abstract 650. VISTA Trial: VMP vs. MP These results establish VMP as another option for patients not eligible for SCT.
    34. 34. 34 • Randomized multicenter Phase III ECOG E4A03 study – RD arm (223 patients) • Lenalidomide 25 mg (days 1-21) • Dexamethasone 40 mg (days 1-4,9-12,17-20) – Rd arm (222 patients) • Lenalidomide 25 mg (days 1-21) • Dexamethasone 40 mg (days 1,8,15,22) – Primary endpoint: response rate at 4 months Lenalidomide/Dexamethasone (RD) vs Lenalidomide/Low-Dose Dexamethasone (Rd) in Transplant-Ineligible Patients Rajkumar et al, Blood 2007 110: Abstract 74
    35. 35. 35 Results From Lenalidomide/Dexamethasone (RD) vs Lenalidomide/Low-Dose Dexamethasone (Rd) Efficacy RD Rd 1-year Survival 88% 96% 2-year Survival 75% 87% OS in Pts<65 (1 year) 92% 97% OS in Pts>65 (1 year) 83% 94% Deaths 42 16 Rajkumar et al, Blood 2007 110: Abstract 74; Jacobus et al., Blood 2008 112: Abstract 1740 Toxicity (Grade >3) RD (N=223) Rd (N=222) Neutropenia 2.7% 3.2% Thrombocytopenia 1.8% 1.4% DVT/PE 25.6% 11.4% Atrial Fibrillation/Flutter 3.1% 0.0% Infection/Pneumonia 16.1% 9.0% Fatigue 11.7% 4.1% Hyperglycemia 5.8% 2.3% Neuropathy 0.4% 1.4%
    36. 36. 36 Results From RD vs Rd Rajkumar et al, Blood 2007 110: Abstract 74; Jacobus et al., Blood 2008 112: Abstract 1740 • Rd is associated with superior OS compared to RD in NDMM patients. • Increased mortality in RD arm is due to disease progression as well as increased toxicity. – Prevention of venous thrombotic events is a priority for both combinations.
    37. 37. 37 Emerging New Treatments in Early Development • Single agents are limited in efficacy, likely to be used in combinations. – Bortezomib, lenalidomide, and thalidomide are being explored for combination regimens. • Combining agents directed at different targets may provide synergistic response without an increase in side effects. ASH 2008 Highlights for Physicians
    38. 38. 38 Bortezomib/Lenalidomide/Dexamethasone in Patients Who Are Transplant Eligible • First-line Phase I/II study assesses safety and efficacy (66 patients). – Lenalidomide 15 to 25 mg (days 1-14) – Bortezomib 1.0 to 1.3 mg/m2 (days 1, 4, 8, 11) – Dexamethasone 40/20-mg (cycles 1-4/5-8) (days 1, 2, 4, 5, 8, 9, 11, 12) – Up to 8 21-day cycles • Manageable toxicities – All G3/4 hematological (3-15%) – G3 hypophosphatemia (8%) – DVT/pulmonary embolism (5% with daily aspirin) – No treatment-related mortality • Overall response rate was 98% (at maximum planned dose – 100%) – VGPR 71% – CR/nCR 36% VRD was efficacious and well-tolerated in NDMM patients. Richardson et al, Blood 2008 112: Abstract 92
    39. 39. 39 Bortezomib/Lenalidomide/Dexamethasone vs Bortezomib/Dexamethasone Study in Transplant-Eligible Patients • Randomized, multicenter Phase III study ECOG E1A05 (initiated in August 2008) – Consolidation therapy for patients after dexamethasone- based induction. – VRD regimen • Bortezomib 1.3 mg/m2 (days 1, 4, 8, 11) • Lenalidomide 15 mg (days 1-14) • Dexamethasone 40 mg (days 1, 8, 15) – VD regimen • Bortezomib 1.3 mg/m2 (days 1, 4, 8, 11) • Dexamethasone 40 mg (days 1, 8, 15) • Primary endpoint: PFS – SCT is deferred until relapse • The strategy will further prolong survival. Fonseca and Rajkumar, Clin Lymphoma and Myeloma 2008 5: 315-317
    40. 40. 40 MPT vs MPR in Patients Who Are Transplant Ineligible • Randomized multicenter Phase III ECOG E1A06 study – MPT regimen • Melphalan (days 1-4) • Prednisone (days 1-4) • Thalidomide (days 1-28) – MPR regimen • Melphalan (days 1-4) • Prednisone (days 1-4) • Lenalidomide (days 1-21) – 28 days for up to 12 cycles – Primary objective: PFS, OS
    41. 41. 41 VMP vs. VTP Mateos et al. Blood 2008 112: Abstract 651 Exploring Alkylating (Melphalan) and Immunomodulatory (Thalidomide) Combinations With Bortezomib in Phase III Study in Elderly Transplant-Ineligible Patients • Study Design – VMP Arm (80 patients): • IV Bortezomib 2x weekly for 1 6-week cycle • IV Bortezomib 1x weekly for 5 5-week cycles + oral Melphalan/Prednisone 1xd on days 1-4 of each cycle – VTP Arm (87 patients): • IV Bortezomib 2x weekly for 1 6-week cycle • IV Bortezomib 1x weekly for 5 5-week cycles + oral Prednisone 1xd and continuous Thalidomide on days 1-4 of each cycle • Primary End Point – Overall response rate (ORR)
    42. 42. 42 Results VMP VTP P Value ≥G3 Neutropenia 34% 19% p=0.009 ≥G3 Thrombocytopenia 21% 9% p=0.01 Non-hematological AE (total) 133 157 p<0.005 ≥G3 Non-hematological AE 25% 32% p=0.04 ≥G3 Cardiac toxicity 0% 7% N/A ≥G3 Thromboembolic events <1% 3.4% N/A ≥G3 Peripheral neuropathy 9% 15% N/A Treatment discontinuation due to AE (patients) 8 16 p=0.08 Conclusions From VMP vs. VTP 6 cycles: 31 weeks of treatment) Mateos et al. Blood 2008 112: Abstract 651 • Incidence of non-hematological AE (especially cardiac) was higher in the VTP arm, resulting in more serious AEs and treatment discontinuations • Thalidomide may not be a partner of choice for Bortezomib - Lenalidomide should be explored
    43. 43. 43 Bortezomib and Vorinostat in Early Clinical Studies • Vorinostat (Zolinza): a synthetic inhibitor of the histone deacetylases (HDACs) – Inhibits cell cycle and survival of cancer cells – FDA-approved for some types of lymphoma • Study design: – Non-randomized, open label, parallel assignment, safety study, treatment, uncontrolled – 34 patients with relapsed/refractory MM • Objectives: – Primary: MTD – Secondary: safety and tolerability as measured by disease progression or unacceptable toxicity during each treatment cycle Weber et al, Blood 2008 112: Abstract 871
    44. 44. 44 Vorinostat Plus Bortezomib: Conclusions Combination of Vorinostat plus Bortezomib is active for treatment of multiple myeloma in the early study. Weber et al, Blood 2008 112: Abstract 871 Toxicity Nausea 61.8% Diarrhea 58.8% Thrombocytopenia 50% Vomiting 50% Efficacy Partial response (PR) 26% Minimal response (MR) 21% Stable disease (SD) 53% Duration SD (days) 160 Range (days) 9 – 369
    45. 45. 45 • New combinations of novel therapies may offer personalized targeted therapy by inhibiting specific pathways in myeloma development – Bortezomib and Thalidomide have moved from the relapsed/refractory indications to first-line therapy positions – Lenalidomide is expected to follow • The trend is to use novel drugs and established chemotherapies in combinations • MM is perceived as a chronic, long-term disease Future Direction of New Therapy Combinations & Protocols of Novel Therapies ASH 2008 Highlights for Physicians
    46. 46. 46 Conclusions • Novel combination therapies have great potentials in improving response rate, time to progression, progression-free survival, and overall survival outcomes. • Randomized clinical trials are needed to compare which of these novel combinations will offer patients better OS balanced with a good quality of life.
    47. 47. 47 Management and Treatment of Emergent Side Effects and Defining Long-Term Effects of Multiple Myeloma Beth Faiman, MSN, APRN-BC, AOCN Cleveland Clinic Taussig Cancer Institute Cleveland, OH
    48. 48. 48 Five Major Categories of Side Effects for Novel MM Treatments • Myelosuppression • Thromboembolic events • Peripheral neuropathy • Gastrointestinal side effects • Steroid-associated side effects • Challenge for nursing management of emergent side effects: – Lack of effective practitioner-based guidelines produces a barrier to providing optimal patient care IMF-NLB ‘Consensus Statements’ CJON June 2008
    49. 49. 49 Myelosuppression: Definition and Symptoms; NLB Consensus Recommendations. CJON June 2008 Marrow Red Blood Cells White Blood Cells Platelets Anemia – Fatigue, malaise and SOB Neutropenia – Increased risk of bacterial, fungal, and viral infections Thrombocytopenia – Bruising and bleeding Neutrophil Eosinophil Lymphocyte Monocyte Basophil
    50. 50. 50 Management of Myelosuppression Risk of Grade 3 and 4 Myelosuppression With Novel Therapies Anemia Neutropenia Thrombocytopenia Thalidomide/Dexamethasone 16% 13% 4% Lenalidomide/Dexamethasone 8% 21% 10% Bortezomib 12% 14% 32% Adapted from NLB Consensus Recommendations. CJON June 2008 Thalomid® Prescribing Information, Revlimid® Prescribing Information, Velcade® Prescribing Information. • General recommendations: – Monitor signs and symptoms – Monitor CBC – Educate on signs and symptoms • Myelosuppression management: – Growth factor therapy – Dose reduction as appropriate – Transfusion as indicated
    51. 51. 51 Overview of Thromboembolic Events • 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 novel therapies: • Thalidomide • Lenalidomide • Measures to prevent novel therapy-associated TE events include: – Mechanical – Myeloma regimen-related – Anticoagulant therapy (clot-preventing) Adapted from NLB Consensus Recommendations. CJON June 2008. Amir Qaseem et al., 2007, Ann Fam Med; J. B. Segal et al., 2007, Ann Intern Med. TE events are serious and potentially life-altering and life-threatening.
    52. 52. 52 DVT/PE: Signs/Symptoms • Slight fever • Tachycardia • Unilateral swelling, erythemia, warm extremity • Cyanosis/cool skin • Distension of superficial venous collateral vessels Adapted from NLB Consensus Recommendations. CJON June 2008 • Anxiety • Sudden dyspnea • Chest discomfort • Tachycardia, tachypnea • Low-grade fever PE IS AN EMERGENCY
    53. 53. 53 Peripheral Neuropathy: Definition, Signs, and Symptoms • Signs/symptoms: – Temporary Numbness – Tingling – Parasthesias – Sensitivity to touch – Muscle weakness • Severe symptoms: – Burning pain – Muscle wasting – Paralysis – Organ dysfunction Adapted from NLB Consensus Recommendations. CJON June 2008; Thalomid® Prescribing Information, Velcade® Prescribing Information; Colson et al., 2004, CJON; S. Lonial, 2007, The American Journal of Hematology/Oncology Damage to the peripheral nervous system, including any injury, inflammation, or degeneration of peripheral nerve fibers Thalidomide/bortezomib can cause peripheral neuropathy
    54. 54. 54 General Strategic Recommendations for the Management of PN Adapted from NLB Consensus Recommendations. CJON June 2008; NCCN 2007; NINDS, 2007; Tariman, 2003, Clinical Journal of Oncology Nursing; Visovsky et al., 2007, Non-Pharmaceutical • Gentle massage of affected areas with cocoa butter, capsaicin cream • Home health referral to review safety at home • Assistance with ADL • Referrals: pain management, neurology, physical/occupational therapy •Ongoing evaluation •Dose and schedule modifications •Pharmacological interventions •Non-pharmacological interventions •Patient education 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 – Amino acids on an empty stomach – Neurontin® , Lyrica® , Cymbalta® – Lidoderm® patch 5% to affected area every 12 hours
    55. 55. 55 Gastrointestinal Side Effects of Novel Therapies Drug Incidence of Gl AEs (All Grades) Constipation Diarrhea Nausea Vomiting Lenalidomide/Dexamethasone 39% 29% 22% 10% Thalidomide/Dexamethasone 55% 12% 28% 12% Bortezomib 42% 57% 57% 35% Thalomid® Prescribing Information, Revlimid® Prescribing Information, Velcade® Prescribing Information Adapted from NLB Consensus Recommendations. CJON June 2008
    56. 56. 56 Management of Diarrhea • Non-pharmacologic – Increase fluid intake – Avoid caffeinated, carbonated, or heavily sugared drinks – Dietary changes: avoid fiber • Pharmacologic – Caution 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 2008; ASCO’s Curriculum Diarrhea 2005; Bush, 2004, Oncology Nursing Forum; Engelking, 2004, Cancer Symptom Management; Mercadante, 2007, Principles & Practice of Palliative Care & Supportive Oncology.
    57. 57. 57 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 Adapted from NLB Consensus Recommendations. CJON 2008; ASCO’s Curriculum Nausea and vomiting 2005; NCI Nausea and vomiting 2007 • 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
    58. 58. 58 Overview of Steroid Side Effects • Steroid classes: – Glucocorticosteroids – Corticosteroids – Used as single agents and in combos • Dexamethasone, Prednisone, Prednisolone Adapted from NLB Consensus Recommendations. CJON June 2008; Alexanian, Dimopoulos, Delasalle, & Barlogie, 1992 • Use of steroids can cause multiple system side effects, such as: –Ophthalmic –Gastrointestinal –Endocrine –Cardiovascular –Dermatologic – Constitutional – Psychiatric – Immune – Musculoskeletal – Bone loss – Body image
    59. 59. 59 Management of Steroid-Dependent Side Effects: Constitutional – • Steroids affect every system • Psychological: –Mood alterations, let-down effect, insomnia • GI: flatulence/hiccoughs • Musculoskeltal: proximal myopathy and muscle cramping • Bone: osteonecrosis, osteoporosis • Endocrine: hyperglycemia, hypogonadism, sexual dysfunction • CV: edema Adapted from NLB Consensus Recommendations. CJON June 2008; Mitchell et al. 2006; Page et al 2006; Badger et al 2006; Cerullo, 2007
    60. 60. 60 Overall Recommendations for the 5 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 that can lead to prolonged hospitalization, and increased morbidity and mortality Adapted from NLB Consensus Recommendations. CJON June 2008; Ghobrial, et al. (2007) Oncology, 21, 785-792. Lonial, S. (2007) The American Journal of Hematology/Oncology, 6, 194-196.
    61. 61. 61 Developing a Nurse-Centric Model for a Survivorship Care Plan Evidence-based data for 5 major long-term side effect issues and their management: creation of clinical practice-based consensus documents Outcome: Survivorship Care Plan and Manuscript Functional Mobility Sexuality & Sexual Dysfunction Bone Health Renal Complications Health Maintenance
    62. 62. 62 Functional Mobility in Multiple Myeloma • Multiple myeloma is mainly a disease of the bone. • Multiple myeloma mostly affects the elderly population, which greatly exacerbates limited motility. • Factors contributing to high risk of falls in elderly MM patients: – Sensory issues (poor vision and hearing) – Age-related co-morbidities • Cardiovascular • Diabetes • Osteoporosis • Hormonal status • Parkinson’s disease • Dementia • Urinary incontinence (fall-related) • Arthritis – Nutrition (muscle weakness, weight loss) – Psychological issues and lifestyle
    63. 63. 63 Reported Mobility-Affecting Side Effects of Novel MM Treatments Common SE Peripheral neuropathy – Sensory and motor symptoms – Ataxia Muscle wasting – Tone and mass – Strength and motor function Myelosupression – Thrombocytopenia – Neutropenia – Anemia Gastrointestinal symptoms – Nausea, vomiting, constipation, diarrhea – Dehydration, anorexia, weight loss – Hypercalcemia, hypokalemia, hyponatremia Fatigue and somnolence Cardiovascular issues – Deep vein thrombosis Impact on Functional Mobility Self-limiting mobility due to: – discomfort or prescribed limitations by the health practitioner – pain and/or discomfort Lack of desire to participate in activity and inability to mobilize safety. Lack of ability to withstand extended activity and may require oxygen. Inability to participate in activities due to organ-function restrictions as prescribed by health care provider. Mobility restrictions due to the symptoms and/or cognitive, muscular impact due to imbalance. Difficulty in desire or ability to participate in activities of daily living, including exercise, diet, etc, and impact on overall quality of life.
    64. 64. 64 Functional Mobility: A Case Study • Annie is a 68-year-old woman with relapsed myeloma receiving bortezomib and dexamethasone. • After 6 cycles she is in a near complete remission but developed painful neuropathy in her feet. – Reported numbness, burning, shooting pain • Doesn’t feel like participating in usual activities due to pain, sits all day. • Husband is afraid she is “giving up;” she has lost her balance twice this week.
    65. 65. 65 What are we most concerned about with Annie? a) Risk of falls due to pain and decreased sensation in her feet can lead to bleeding with low platelets. b) Risk of pneumonia due to inactivity. c) Depression. d) Neuropathy may limit the amount of treatment she is able to receive. e) All of the above. Functional Mobility: A Case Study
    66. 66. 66 Bone Health and Bone Disease • Bone disease is a hallmark of multiple myeloma • Caused by defects in the balance between bone formation and resorption – Skeletal events may progress despite an efficacious treatment. • Main manifestations of bone disease (at diagnosis): – Diffuse osteopenia and/or focal lytic lesions (70-80%) – Pathological fractures • Most common site is spine (55-70%) – Hypercalcemia (30%) – Bony pain (60%)
    67. 67. 67 Bone Health and Bone Disease: A Case Study • JJ is a 76-year-old man diagnosed in 2001 with IgG Kappa Myeloma. • Prior therapies (3): thalidomide, bortezomib, lenalidomide • Bisphosphonates every 3 months (pamidronate) • While moving furniture he experiences 10/10 pain in his back. • Dx: L2 compression fracture • Balloon kyphoplasty is recommended; patient declines. • He receives a prescription for pain medication.
    68. 68. 68 Bone Health and Bone Disease: A Case Study What would be the most important consideration for this elderly patient with a compression fracture? a) Increased risk for DVT while on lenalidomide. b) Increased risk for pneumonia due to altered skeleton (kyphosis). c) Pain will decrease his ability to perform ADLs. d) All of the above.
    69. 69. 69 Renal Complications One of the common clinical features of symptomatic myeloma. • 20 to 60% of patients present with renal complications. – Elevated serum creatinine level – Anemia, fatigue – Fluid and electrolyte imbalances – Light-chain proteinurea • Proteinurea may lead to end-stage renal disease (ESRD) and dialysis. • Reasons for kidney failure: – Monoclonal immunoglobulin deposition disease (MMID) – Amyloidosis – Light-chain deposition disease (LCCD) – Acute tubular necrosis (ATN)
    70. 70. 70 Renal Complications: A Case Study • Jane is a 43-year-old woman diagnosed with kappa light chain MM in 1998 • Received 2 stem cell transplants in late 2001 and early 2002; she has been in remission since. • Blood work every 3 months, stable • Called complaining of nausea, vomiting, and fevers in the last 48 hours
    71. 71. 71 Renal Complications: A Case Study • Labs: – WBC 3.9 k/uL – Hemoglobin 7.9 g/dL – Platelet count 158 K/uL – Creatinine 3.9 g/dL (1.9 last month) – Calcium 11.7 mg/dL – Albumin 3.2 g/dL – Beta-2 M 7.9 • Skeletal survey shows progressive disease: scattered lesions calvarium, pelvis and bilateral femurs
    72. 72. 72 Renal Complications: A Case Study She is admitted for IV hydration and a blood transfusion She receives a pulse of dexamethasone and pamidronate for hypercalcemia of malignancy (HCM) What would you anticipate next? a) Lenalidomide and Dexamethasone b) Bortezomib and Dexamethasone c) Bortezomib and pegylated liposomal Doxorubicin d) Enroll in a clinical trial with an experimental agent
    73. 73. 73 Sexuality & Sexual Dysfunction • Sexual dysfunction (SD) is characterized by those psychological and physiological changes that negatively impact sexuality. • Publications regarding SD in cancer patients are limited • SD is not part of the normal aging process!! It is a result of physical illness and/or psychological factors • Types of SD (according to the DSM IV): – Sexual desire disorder (decreased libido) – Sexual arousal disorder – Orgasm disorder – Sexual pain disorder
    74. 74. 74 The Impact of Myeloma Treatment on Sexuality • Thalidomide – Reported to induce impotence in male patients • Bortezomib and lenalidomide – Unpublished reports of erectile dysfunction and decreased libido • Sildenafil has positive results in restoring proper functioning • Our knowledge of the effects of novel myeloma treatment on sexuality is very limited – Patients are reluctant to discuss the issue – Sexuality assessments are not performed Murphy and O’Donnell, Haematologica, 92 (10), 2007
    75. 75. 75 Sexual Dysfunction: Communication is Critical • There is an urgent need for open communication between physicians, nurses, and their patients – Multiple well-established treatments for ED are available for male and female patients • Stressors can lead to depression in men and women • Patients may be unable or unwilling to verbalize this as a side effect • This is often placed on the back burner, as treatment is most important • Ask your patients!!
    76. 76. 76 Sexuality and Sexual Dysfunction: A Case Study • Mrs. D is a 53-year-old woman diagnosed 3 years ago with MM. After a long remission, she relapsed and is now 2 months post stem cell transplant • Mr. D uncomfortably asks you if he and his wife “will ever be able to have sex again.” • Mrs. D says that she feels no desire and that when they tried to have sex 3 weeks ago, she did not feel stimulated and found it to be painful. Becomes teary eyed; their sexual relationship has been strained since her diagnosis 3 years ago. Mr. D told her that he “can’t take it anymore.”
    77. 77. 77 Sexuality and Sexual Dysfunction: A Case Study How would you approach this? a) Think of Mr. D as being selfish after all his wife has been through b) Avoid the question because Mrs. D starts crying. It’s a hard topic for her c) Refer the couple to a social worker, who knows more than you d) Pull up a chair and ask Mrs. D, “How do you feel?”
    78. 78. 78 Understanding and Optimizing Survivorship Care Tiffany Richards: MS, ANP, AOCNP MD Anderson Cancer Center Houston, TX
    79. 79. 79 Definition of Cancer Survivor “An individual is considered a cancer survivor from the time of diagnosis through the balance of his or her life. Family members, friends, and caregivers impacted by the survivorship experience are included.” (NCI, 2004)
    80. 80. 80 3 “Seasons of Survival” (Mullan) • Acute survival: Diagnosis treatment – Fear and anxiety – Confrontation of mortality – Family needs • Extended survival: watchful waiting, consolidation, or intermittent therapy – Fear of recurrence – Physical limitations adaptation to work and home – Experiences variable • Permanent survival: “cure” – Insurance and employment problems – Long-term effects of therapy Mullan, NEJM 1985
    81. 81. 81 Comparisons of Patient and Physician Expectations for Cancer Survivorship Care Investigators from the Harvard School of Public Health, Dana-Farber Cancer Institute, and the Institute of Clinical Evaluative Sciences (Toronto) conducted a study to compare expectations regarding survivorship care among PCPs, oncologists, and patients • The results demonstrated a lack of agreement among these constituents with respect to their roles in ongoing survivor care. • The discordance was particularly high between patients and their oncologists. The underlying causes for the discrepancies were unclear.
    82. 82. 82 Cancer Survivorship: From Individual to Experience • Defined as: – A time frame – A stage or phase – An outcome • Must take into account: – Maintenance therapy – Incurable but treatable cancers – Regimen changes – Recurrences – Secondary tumors – Late effects of treatments
    83. 83. 83 Institute of Medicine (IOM) Findings: Survivorship Care • Survivorship care is neglected. • Cancer recurrence, second cancers, and late effects of treatment. • Few guidelines. • Providers lack education. Shulman & Ganz ASCO Survivorship Models 2008
    84. 84. 84 • Survivors: – Unaware of risk – No plan for follow-up • Missed opportunities • Lack of care coordination IOM Findings: Survivorship Care (cont’d) Shulman & Ganz ASCO Survivorship Models 2008
    85. 85. 85 IOM Findings: Survivorship Care (cont’d) • Chronic care model • Essential care components: – Prevention – Surveillance – Intervention – Coordination Shulman & Ganz ASCO Survivorship Models 2008
    86. 86. 86 IOM Findings: Survivorship Care (cont’d) IOM Recommendation: • “All patients completing Rx should receive a comprehensive treatment summary & care plan.” Shulman & Ganz ASCO Survivorship Models 2008
    87. 87. 87 Reasons for a Survivorship Care Plan • Summarize treatment • Communicate late effects of treatment • Promote continuous communication between patients and healthcare providers • Promote a healthy lifestyle – Prevent recurrence – Reduce risk of co-morbid conditions Shulman & Ganz ASCO Survivorship Models 2008
    88. 88. 88 Key Elements for an Effective Survivorship Care Plan Shulman & Ganz ASCO Survivorship Models 2008 • Diagnosis and stage • Treatment plan and dates • Expected short- and long-term effects • Late toxicity monitoring • Surveillance for recurrence or second cancer • Responsibility for survivorship care • Psychosocial and vocational needs • Recommended preventive behaviors and recommendations
    89. 89. 89 IOM Recommendations for Quality Healthcare in America • Care based on continuous healing relationships • Customized care • Patient as source of control • Shared knowledge and information • Evidence-based decision making • Safety as a system property • Transparency • Anticipation of needs • Continuous decrease in waste • Cooperation
    90. 90. 90 Quality Healthcare = Optimal Survivorship Care • Receipt of optimal survivorship care depends on a patient-centered approach (Berry et al., 2003). • Call for such an approach has been made by physician-researchers William Tierney and Elizabeth McKinley in their description of their cancer experience from the patient’s perspective (Tierney and McKinley, 2002).
    91. 91. 91 Essentials of Survivorship Care • Prevention and detection of new cancers and recurrence • Intervention for consequences of cancer and its treatment (eg, osteoporosis) • Coordination between specialists and primary care providers
    92. 92. 92 Barriers to Cancer Survivor Care • For the Cancer Survivor: – Fragmented delivery system – Lack of awareness – Barriers to communication • For the Provider: – Fragmented delivery system – Lack of education/training – Lack of survivorship standards of care – Capacity to deliver survivorship care
    93. 93. 93 Challenges to Survivorship Care • As lives are extended, so too are the risks of developing late or delayed effects. • Major questions - who will be responsible for: – Monitoring patient’s health – Assisting in recovery – Making referrals – Paying for continued care Leigh, Cancer Survivorship: A Nursing Perspective, in Cancer Survivorship Today and Tomorrow, 2007
    94. 94. 94 Why Survivorship Care for Multiple Myeloma? • 2008 expectations for MM patients: – >90% response upfront – CR + VGPR ≥60% – 3-year survival 80 to 90% – 6-year survival 60 to 70% – >10-year survival 30 to 40% Increased survival leads to the need for new approaches to quality survivorship care
    95. 95. 95 Survivorship Care Continuum Individuals with chronic or intermittent disease may receive ongoing treatment for their disease, but benefit from survivorship care as they live with their disease Prevention Diagnosis Initial treatment Continuing care Maintenance Follow-up Recurrence Progressive disease Palliative care Survivorship isn’t a stage!!!! It is a continuum from diagnosis to the end of life
    96. 96. 96 ASCO Tools for Survivorship Care An important component of survivorship care is a patient’s treatment summary
    97. 97. 97
    98. 98. 98 Focus on the Future Sandra Rome, RN, MN, AOCN Cedars-Sinai Medical Center Los Angeles, CA
    99. 99. 99 New Drugs – New Perspective for Multiple Myeloma • Thalidomide • Bortezomib • Lenalidomide Chronic? A Cure??OR Longer follow-up required!!
    100. 100. 100 The Future for Transplant-Eligible Patients VAD Thalidomide Dexamethasone Lenalidomide/low Dexamethasone Bortezomib + Dexamethasone VTD… Old standard New standard Transplant Harvest New combinations NCCN Clinical Practice Guidelines in Oncology, v2 2009
    101. 101. 101 The Future for Transplant-Ineligible Patients MP MPT VMP MPR Lenalidomide/low Dexamethasone Old standard New standard New options NCCN Clinical Practice Guidelines in Oncology, v2 2009
    102. 102. 102 Impact of Novel Therapies on Survivorship Care • Unexpected new long-term complications • Second cancers • Long-term maintenance for survivors: quality of life • Family/social problems • Financial/insurance concerns • Other
    103. 103. 103 Optimizing Survival: Importance of Health Maintenance • MM patients are expected to live longer • Proper health maintenance contributes toward longer survival and quality of life
    104. 104. 104 Risk Factors Affecting Health Maintenance • Lifestyle choices • Mental risk factors – Substance abuse – Depression • Fatigue – Depression, pain, and anemia • Cognitive changes – “Chemo brain” effect • Dermatological issues – Immune system weakened by therapy • Transplants • Radiation – Increased risk for skin cancer
    105. 105. 105 Old Model Survivorship as a stage: • Decreasing contact • Brief check-ups • May not recognize survivorship • Busy clinics – Time constraints – Focus on acutely ill Leigh, Cancer Survivorship: A Nursing Perspective, Cancer Survivorship Today and Tomorrow, 2007 Emerging Model Survivorship as a process: • Contact along the extended continuum of care • Survival plan will be developed shortly after diagnosis • Survivors and families will be supported medically, emotionally, financially. • It is not just about IF and HOW LONG, but HOW WELL?? Shifting Paradigm for Survivorship Care: Nurse Role
    106. 106. 106 Nurse-Centric Model of Survivorship Care* Nursing Roles Emerge as Central to Survivorship Care Patient ResearchPatient Counseling Patient Education Patient ManagementPatient Monitoring Patient Advocacy * Developed by ScienceFirst, LLC; All Rights Reserved ( Nurses are Central to Patient Management and Healthcare Resource Coordination
    107. 107. 107 Nurse-Led Survivorship Care Nurses: • Expert knowledge • Close relationships with patients and families • Understand psychosocial issues • Recommend referral • Work within a model of wellness promotion rather than disease management Leigh, Cancer Survivorship: A Nursing Perspective, Cancer Survivorship Today and Tomorrow, 2007
    108. 108. 108 Nurse-Led Survivorship Care (cont’d) Barriers: • Shortage of trained oncology nurses, especially in outpatient settings • Lack of coordinated care and communication among healthcare providers • Insurance and reimbursement issues Leigh, Cancer Survivorship: A Nursing Perspective, Cancer Survivorship Today and Tomorrow, 2007
    109. 109. 109 National Coalition for Cancer Survivors (NCCS) “Imperatives” NCCS’s “Imperatives for Quality Cancer Care: Access, Advocacy, Action, and Accountability”: • Nurses are major players • Health promotion and wellness are critical in survivor clinics • Continued need for supportive care • Critical value of education and rehabilitation for symptoms: – Fatigue, chronic pain, weight changes, decreased stamina NCCS. Imperatives for Quality Cancer Care: Access, Advocacy, Action, and Accountability, 1996
    110. 110. 110 Nursing-Sensitive Patient Outcomes (NSPO) • ONS defined nursing-specific outcomes for cancer patients: – changes in symptom management, functional status, safety, psychological status, costs Given and Sherwood, 2005; Rutledge, 2005 • NSPO describes “continuum of care:” Prevention Diagnosis Initial treatment Continuing care Maintenance Follow-up Recurrence Progressive disease Palliative care Survivorship isn’t a stage!!!! It is a continuum from diagnosis to the end of life
    111. 111. 111 What is a Survivorship Care Plan? • A document: – Summarizes what transpired during cancer treatment – Gives recommendations for follow-up care • It needs to: – Be prospective – Identify known and potential long-term effects • It aims to: – Promote a healthy lifestyle – Prevent recurrence of cancer – Reduce risk of co-morbid conditions – Ensure adherence to follow-up recommendations Implementing Cancer Survivorship Care Planning
    112. 112. 112 Opportunity to leverage the NLB’s experience by identifying relevant long-term side-effects and developing a Survivorship Care Plan for Multiple Myeloma Meeting the Unmet Need
    113. 113. 113 NLB Developed Consensus Guidelines for Management of Acute Side-Effects NLB determined the 5 most common emergent side effects requiring clinical “Consensus Statement” development Peripheral neuropathy DVT and PE Myelosuppression GI effects Steroid effects IMF-NLB ‘Consensus Statements’ supplemCJON June 2008
    114. 114. 114 • Survivorship Care Plan offers the opportunity to enhance treatment outcome and patient quality of life • Survivorship Care Plan will need to be updated as new therapies emerge A New Horizon in Patient Care
    115. 115. 115 Goals of NLB Survivorship Care Plan How myeloma, treatments, and patient-specific characteristics affect: • Renal disease • Sexuality and sexual dysfunction • Bone metabolism • Safety and functional mobility • Health maintenance
    116. 116. 116 Develop recommendations for schedules of evaluations and evidenced-based interventions: • Prevention, screening through treatment of sequelae • Enable clinicians and patients to optimize therapy by preventing or adequately treating co-morbid conditions. Goals of NLB Survivorship Care Plan (cont’d)
    117. 117. 117 NLB will disseminate this information to those within in the community who can effect the most change: • Patients • Caregivers • Healthcare providers Goals of NLB Survivorship Care Plan (cont’d)
    118. 118. 118 Creation of a MM Survivorship Care Plan • Co-morbid conditions affect: – Treatment options – Survival – Late side effects • The plan will: – Prevent and control • Other cancer diagnosis • Treatment-related outcomes – Late effects of treatment – Second cancers – Suboptimal quality of life – Provide a knowledge base for follow-up care and surveillance – Optimize health after cancer treatment
    119. 119. 119 Multiple Myeloma Survivorship Care Plan • IMF Web site is a source for support and education in all aspects of MM • Resources for survivorship care will be posted on the site
    120. 120. 120 Closing Remarks • Beth Faiman, MSN, APRN-BC, AOCN • Cleveland Clinic Taussig Cancer Institute Cleveland, OH
    121. 121. 121 • Clinical Journal Oncology Nursing (CJON), Supplement 12(3), June 2008 • Patient Education Insert Tear-Out Tools for 5 Side Effects – Myelosupression – Thromboembolic events – Peripheral neuropathy – Gastrointestinal side effects – Steroid-associated side effects PUBLISHED: Managing the Side Effects of Novel Agents for Multiple Myeloma: Guidelines and Patient Education Sheets NLB Accomplishments
    122. 122. 122 Patient Education Tear-Out Tools General format and clinical utility: • Side effect description • Novel therapies that may be associated with the side effect • Signs and symptoms • Risk factors • Healthcare provider recommendations NLB Consensus Statements, CJON June 2008
    123. 123. 123 Future Goals of NLB • Frame the importance of nursing. • Management of long-term side effects associated with MM therapies Develop Survivorship Care Plan Expand initiative to collaborate with nurses worldwide
    124. 124. 124 Focus of NLB Commitment • Five major long-term health risks identified Nurse-Centric Survivorship Care Plan Health maintenance Functional mobility Bone health Renal complications Sexual dysfunctions • Five NLB focus groups are created to investigate the five risk categories and develop recommendation manuscripts
    125. 125. 125 • Publication of the Survivorship Care Plan will be immeasurably valuable to the general nursing community involved in multiple myeloma patient care • Communication and dissemination of the Survivorship Care Plan are important next steps. • Develop new educational materials/tools: - Patient related - Nurse related Focus of NLB Commitment (cont’d)
    126. 126. 126 Communication and Dissemination • Patient and nurse educational slide set development • NLB Speaker’s Bureau • Oncology conference presentations • ONS Web site: - • IMF Web site: -
    127. 127. 127 Educational Resources • American Cancer Society • National Cancer Institute • International Myeloma Foundation - IMF Myeloma Today Newsletter - (800) 452 CURE - IMF Web site •
    128. 128. 128 Accreditation 1. Symposium Accreditation Process Please complete the CE Certificate Registration and Program Evaluation Form found in the guidebook and return this completed form to the registration desk to receive 2.0 CEU credits 2. CJON Supplement Accreditation Opportunity Please visit and complete the online tests for a maximum of 3.8 additional CEU credits
    129. 129. 129 Acknowledgements • Tiffany Richards • Sandra Rome • Joseph Tariman • International Myeloma Foundation • MER
    130. 130. 130 Question & Answer Session Faculty Panel
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