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Myeloma 101 and Standards of Care for Myeloma

Myeloma 101 and Standards of Care for Myeloma. Joanne Hewitt PhD, NP, CON(C) Nurse Practitioner Cross Cancer Institute October 13, 2018 MASS Education Conference. What Is Multiple Myeloma?. Cancer of the plasma cells in bone marrow Growth of myeloma cells:

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Myeloma 101 and Standards of Care for Myeloma

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  1. Myeloma 101 and Standards of Care for Myeloma Joanne Hewitt PhD, NP, CON(C) Nurse Practitioner Cross Cancer Institute October 13, 2018 MASS Education Conference

  2. What Is Multiple Myeloma? • Cancer of the plasma cells in bone marrow • Growth of myeloma cells: • Disrupts normal bone marrow function • Reduces normal immune function • Results in abnormal production and release of monoclonal protein into blood and/or urine • Destroys and invades surrounding bone Barlogie B, et al. In: Williams Hematology; 2006. Durie BG. IMF 2007.BG. IMF 2007.

  3. Canadian Statistics - 2017 Incidence: Canada: Alberta Total: 2900280 Males: 1700 170 Females: 1200 110 Per 100,000: 7.1 (M = 9.1; F = 5.6) M = 7.9; F = 5.4 Canadian Cancer Society: 2017

  4. Normal Plasma Cell Function Origins of plasma cells Normal immunoglobulin molecule containing paired heavy chains with one smaller light chain attached to each Each mature plasma cell produces thousands if identical Ig every second

  5. Myeloma Plasma Cells Billions of cancer cells each secrete thousands of identical Ig every second NCI : www.cancer.gov/images/cdr/live/CDR763079.jpg

  6. Monoclonal Protein • Also referred to as: • M-protein • Para-protein • M-spike • Bence Jones Proteins (urine light chains) Dr. Henry Bence Jones 1813 – 1873

  7. Kyle & Rajkumar, Blood, 2008 Timeline depicting the history and treatment of multiple myeloma from 1844 to the present.

  8. Bone Destruction • Types of bone cells: • Osteoblasts – make bone • Osteoclasts – break down & remodel bone as bones grow or if there is stress on the skeleton • In normal adult bone, the activity of both of these types of cells is balanced so that bones do nto weaken or keep getting bigger

  9. Renal Impairment • Common – 20-25 % of patients at diagnosis - up to 50% at some time during disease course • Approx. half of these will have some degree of persistent renal impairment, with 2-12% requiring dialysis • Cause: damage to renal tubules by free light chains (cast nephropathy or “myeloma kidney”) • Other factors can also contribute to this damage

  10. Standard Therapy for Newly Diagnosed Multiple Myeloma

  11. Treatment – Transplant Eligible • Induction chemotherapy • Cyclophosphamide, bortezomib, dexamethasone (CyBorD or CVD) for 4 to 6 cycles • Mobilization and collection of peripheral blood stem cells • Transplant • High dose melphalan and autologous stem cell transplant (ASCT) • Consolidation/Remission Maintenance • Lenalidomide • Bortezomib (for those with higher risk cytogenetics (del 17p).

  12. Treatment – Non-Transplant Eligible • Induction chemotherapy • Cyclophosphamide, bortezomib, dexamethasone (CyBorD or CVD) for 9 – 12 cycles • Maintenance • Bortezomib every 2 weeks for 2 years OR • Lenalidomide and dexamethasone OR • Clinical Trial

  13. Getting to Minimal Residual Disease: New Definitions for CR Newly diagnosed 1 x 1012 S.S. Patient Disease burden CR 1 x 108 Stringent CR Bortezomib Lenalidomide Combinations 1 x 104 Molecular/flow CR ?Cure? 0.0

  14. Therapy for Relapsed Disease

  15. Medications Available to Treat Myeloma Monoclonal Antibodies • Daratumumab (iv) Alkylating Agents • Cyclophosphamide (po or iv) • Melphalan (po or iv) • Other Chemotherapy Agents • Doxorubicin (iv) • Etoposide (po or iv) • Cisplatin (iv) Steroids • Dexamethasone (po or iv) • Prednisone (po) Transplant • Autologous stem cell Agarwal A et al. Clinical Lymphoma Myeloma and Leukemia 2016; http://dx.doi.org/10.1016/j.clml.2016.11.010 Proteasome Inhibitors (Pls) Bortezomib (s/c) Carfilzomib (iv) Ixazomib (oral) Immunomodulatory agents (IMiDs) Thalidomide (po) Lenalidomide (po) Pomalidomide (po)

  16. RELAPSED / REFRACTORY MULTIPLE MYELOMA Management Laubach L, et al. Leukemia 2016;30:1005–17; doi:10.1038/leu.2015.356 Nooka AK, et al. Blood 2015;125(20):3085–99. 24 • When to treat? • Treatment indicated when patients develop symptomatic relapse, a rapidly rising monoclonal protein level, or extramedullary disease • General Management: • A patient naïve to an agent (or class of agents) is generally treated with that agent • A second transplant can be considered in selected patients if the benefit from the first exceeds 18-24 months • A patient with relapsed myeloma who has not previously undergone ASCT, can be considered for high-dose therapy (if they can tolerate high-dose therapy) • A patient who responded to a particular doublet with previous duration of response (DOR) of ≥6–9 months can be retreated at relapse with similar agents • Consider adding an alkylator to a doublet regimen if the desired response is not seen • Duration of therapy: • Determined by clinical context • Treatments: • Combine treatments with different mechanisms of action • Depends on previous therapies and response durations, marrow reserve, and comorbidities

  17. General Treatment Principles Patient Considerations Disease Considerations Evidence / Access • Refractory to previous treatment • 1st, 2nd, 3rd relapse • Depth and duration of response • Genetic features of myeloma • Pace of disease • Consider triple therapy where possible • Evidence to support treatment decision • Is clinical trial an option • Funding situation • Patient support systems • Is the patient a transplant candidate? • Comorbidities • Patient adherence • Patient preferences • Side effects of treatment Laubach L, et al. Leukemia 2016;30:1005–17; doi:10.1038/leu.2015.356 Nooka AK, et al. Blood 2015;125(20):3085–99.

  18. Patient and Caregiver Education Landgren, Medscape Education, 2016

  19. Contributing Factors to Fatigue Borneman 2013 Journal of Hospice & Palliative Nursing

  20. Kurtin, S., APSHO Regional Lecture Series

  21. Summary Chronic disease with need for continuous therapy & regular hospital visits, blood tests, F/U visits with various HCPs • Drug therapy monitoring: • Medication review for drug interactions • Adjust regimens as needed for renal dysfunction • Adherence: drug calendars & patient buy-in for continuous therapy • Ensure proper monitoring of blood counts requiring dose adjustments • Patient education: • Educate patients on adverse events and strategies for managing them • Education on how to take multi-drug treatments properly • Reinforce adherence with oral regimens • Supportive care: • Nausea/vomiting, anemia, pain management, etc • Prophylactic anticoagulation when required, monitoring and adjustment of doses • Viral prophylaxis • Bisphosphonates • Monitor for infection Ashjian E, Redic K. J Oncol Pharm Practice 2016;22(2):289-302.

  22. THANK YOU

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