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Practical Navigation of a Changing Landscape: Keeping Current on Multiple Myeloma Treatments

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The vital role of oncology nurses in the care of patients with MM necessitates the awareness of the latest treatment advances and best practices for side-effect management. This CE-certified activity will provide updates in first-line, maintenance, and relapsed/refractory settings. Expert faculty will articulate the diagnosis, cytogenetics, and staging of the disease, as well as promising novel agents and evidence-based best practices for the management of side effects. To provide insight to attendees of the impact of evolving data on a personal level, a patient with MM will share personal perspectives on the journey from diagnosis, treatment, and overall patient experience.

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Review a downloadable slide deck by Beth Faiman, PhD(c), RN, APRN, BC, AOCN®, covering the most clinically relevant new data reported from Practical Navigation of a Changing Landscape: Keeping Current on Multiple Myeloma Treatments.

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This activity has been designed to meet the educational needs of oncology nurses involved in the care of patients with multiple myeloma (MM).

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This slide deck in its original and unaltered format is for educational purposes and is current as of May 2012. All materials contained herein reflect the views of the faculty, and not those of IMER, the CE provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice, diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity.

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Practical Navigation of a Changing Landscape: Keeping Current on Multiple Myeloma Treatments

  1. 1. DISCLAIMER This slide deck in its original and unaltered format is for educational purposes and is current as of May 2012. All materials contained herein reflect the views of thefaculty, and not those of IMER, the CME provider, or the commercial supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. Readers should not rely on this information as a substitute for professional medical advice,diagnosis, or treatment. The use of any information provided is solely at your own risk, and readers should verify the prescribing information and all data before treating patients or employing any therapeutic products described in this educational activity. Usage Rights This slide deck is provided for educational purposes and individual slides may be used for personal, non-commercial presentations only if the content and references remain unchanged. No part of this slide deck may be published in print or electronically as a promotional or certified educational activity without prior written permission from IMER. Additional terms may apply. See Terms of Service on IMERonline.com for details.
  2. 2. DISCLAIMER Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. DISCLOSURE OF UNLABELED USE This activity may contain discussion of published and/or investigational uses ofagents that are not indicated by the FDA. IMER does not recommend the use of any agent outside of the labeled indications.The opinions expressed in the activity are those of the faculty and do not necessarily represent the views of IMER. Please refer to the official prescribing information foreach product for discussion of approved indications, contraindications, and warnings.
  3. 3. Disclosure of Conflicts of Interest Beth Faiman, PhD(c), RN, APRN, BC, AOCN®, reported a financial interest/relationship or affiliation in the form of: Consultant, Celgene Corporation, Millennium Pharmaceuticals, Inc.; Speakers Bureau, Celgene Corporation, Millennium Pharmaceuticals, Inc., Ortho Biotech Products, L.P. Page Bertolotti, BSN, RN, OCN®, reported a financial interest/relationship or affiliation in the form of: Speakers Bureau, Celgene Corporation, Millennium Pharmaceuticals, Inc. Pat Killingsworth, has no real or apparent conflicts of interest to report.
  4. 4. Activity OverviewBeth Faiman, PhD(c), RN, APRN, BC, AOCN® Cleveland Clinic Taussig Cancer Institute
  5. 5. Learning Objectives Upon completion of this activity, participants should be better able to: Discuss the risk factors, staging, prognostic factors, and cytogenetics of MM Describe recent research in the treatment of patients with newly diagnosed MM Identify new combination therapies for patients who are not candidates for transplant Assess new options for treating patients with relapsed/refractory MM Identify the role and timing of stem cell transplant in MM Outline an evidence-based nursing care plan for MM patients based on common disease and treatment-related symptoms Describe potential side effects from MM treatment with patients and the recommendations for their management
  6. 6. Introduction to Faculty Panel Beth Faiman, PhD(c), RN, APRN, BC, AOCN® (Chairperson) – Nurse Practitioner – Cleveland Clinic Taussig Cancer Institute Page Bertolotti, BSN, RN, OCN® – Oncology Nurse Coordinator – Samuel Oschin Cancer Center at Cedars-Sinai Medical Center Sundar Jagannath, MD – Multiple Myeloma Program Director – Mount Sinai School of Medicine Pat Killingsworth (Patient Speaker) – Columnist for the Myeloma Beacon
  7. 7. Activity Agenda 6:00 – 6:05 AM Welcome and Activity Overview 6:05 – 6:20 AM Diagnosing Multiple Myeloma 6:20 – 6:40 AM The Evolving Landscape of Myeloma Treatment: First-Line 6:40 – 6:50 AM The Evolving Landscape of Myeloma Treatment: Maintenance Therapy 6:50 – 7:10 AM The Evolving Landscape of Myeloma Treatment: Relapsed/Refractory Disease 7:10 – 7:25 AM Patient Perspective 7:25 – 7:30 AM Questions and Answers
  8. 8. Diagnosing Multiple Myeloma Page Bertolotti, BSN, RN, OCN® The Samuel Oschin Cancer Center at Cedars-Sinai Medical Center
  9. 9. Multiple Myeloma (MM) Overview  A malignant proliferation of a single clone of plasma cells that arise from B cells in the bone marrow  Extensive skeletal destruction results in bone pain, fractures, spinal cord compression and hypercalcemia  End organ damage best remembered by the mnemonic CRAB – Calcium – Renal – Anemia – Bone impairmentKyle et al, 2009; Nau et al, 2008.
  10. 10. Clinical Presentation Disease Process Clinical Presentation M protein in serum or urine (97%) Hyperviscocity with excessive M protein in the blood (common in IgA myeloma) Clonal plasma cells (96%) > 10% plasma cells in bone marrow Skeletal involvement (80%) Pain, reduced height, lytic lesions, pathologic fractures, osteoporosis, hypercalcemia Anemia: Hgb < 12 g/dL (40%–73%) Weakness, fatigueHgb = hemoglobin.Dispenzieri et al, 2009; Nau et al, 2008; Rajkumar, 2011.
  11. 11. Clinical Presentation (cont.) Disease Process Clinical Presentation Renal insufficiency (20%–25%): light Serum creatinine 2 mg/dL or greater chain cast nephropathy (myeloma kidney) and hypercalcemia Hypercalcemia: Calcium > 11 mg/dL Anorexia, nausea, lethargy, polydipsia (13%–30%) (excessive thirst), constipation, confusion Neuropathy (20%) Numbness, tingling, carpal tunnel syndrome (consider amyloidosis) Immune function deficiency Recurrent infections, bacteremia, (0.8–1.4 infections per patient-year) pneumonia; “tumor fever” in < 1%Dispenzieri et al, 2009; Nau et al, 2008; Rajkumar, 2011.
  12. 12. Risk Factors Age Median 65–70 years Race Twice as likely in African Americans than Caucasians Gender Slightly more common in men than women Genetics Higher risk in those with a first-degree relative with MM Exposures Ionizing radiation, pesticides, herbicides, fungicides, benzene, petroleum, hair dyes, engine exhaust, furniture worker products Other Factors Obesity and chronic immune stimulation such as systemic lupus erythematosusKyle et al, 2012; Rajkumar, 2011; Tariman, 2010; Okali et al, 2009.
  13. 13. Diagnostic Evaluation  Complete history and physical  Laboratory tests  BMB and aspirate – Immunophenotyping: Flow cytometry and protein expression – Conventional cytogenetics: Chromosome analysis, deletions, and karyotype – FISH: Genetic mapping and translocations – PCLI if available  ImagingBMB = bone marrow biopsy; FISH = fluorescent in situ hybridization; PCLI = plasma cell labeling index.Kyle et al, 2012; Dispenzieri et al, 2009; NCCN, 2012.
  14. 14. mSMART Risk Stratification of MM High Risk Intermediate Risk Standard Risk FISH FISH All other including: del(17p) t(4;14) Hyperdiploidy t(14;16) Cytogenetic del(13) or t(11;14) hypodiploidy t(14;20) t(6;14) PCLI > 3% GEP High-risk signaturemSMART = Mayo Stratification of Myeloma and Risk-Adapted Therapy; GEP = gene-expression profiling.Dispenzieri-Kumar et al, 2011.
  15. 15. Laboratory Tests Lab Tests Common Findings CBC with differential Anemia (80%) Complete metabolic panel, Elevated creatinine (19%), phosphorus, uric acid hypercalcemia (13%), low albumin LDH Tumor burden β2m Tumor burdenCBC = complete blood count; LDH = lactate dehydrogenase; β2m = beta-2-microglobulin.Kyle et al, 2012; Tariman et al, 2010; Dispenzieri et al, 2009.
  16. 16. Laboratory Tests (cont.) Lab Tests Common Findings SPEP M spike in the beta or gamma region; 97% monoclonal heavy or light-chain protein; < 3% nonsecretory Quantitative immunoglobulins (Igs) IgG (52%), IgA (21%), IgM (< 1%), IgD (2%) SIFE Identifies light/heavy chain types of the M protein Serum FLC Lambda, kappa, and ratio (20% only light chain disease) 24-hour urine: Total protein, UPEP, UIFE Urinary M protein (Bence-Jones proteinuria); 20% lack serum M protein but have urinary M protein; involves renal impairmentSPEP = serum protein electrophoresis; SIFE = serum immunofixation electrophoresis; FLC = free light chain assay;UPEP = urine protein electrophoresis; UIFE = urine immunofixation.Kyle et al, 2012; Tariman et al, 2010; Dispenzieri et al, 2009; Reece et al, 2012.
  17. 17. Imaging Test Finding Skeletal survey Extent of bone involvement (head-to-toe X rays of axial bones), osteolytic lesions, osteopenia, osteoporosis Bone density Bone loss MRI Location and size of plasmacytomas, fractures, R/O cord compression PET Extent of disease and response to treatment; useful in nonsecretory diseaseMRI = magnetic resonance imaging; PET = positron emission tomography; R/O = rule out.Kyle et al, 2012; Dispenzieri et al, 2009; Durie, 2011.
  18. 18. IMWG Diagnostic Criteria Diagnosis Criteria (all 3 required) MGUS < 3 g/dL M protein; < 10% clonal plasma cells; no end organ damage Smoldering (asymptomatic) ≥ 3 g/dL M protein; ≥ 10% clonal plasma cells; no end myeloma organ damage Active (symptomatic) myeloma > 10% clonal plasma cells M protein in serum and/or urine (unless nonsecretory); At least 1 of the following CRAB features: C - Calcium > 11.5 mg/L R - Renal dysfunction, serum creatinine > 2 mg/dL A - Anemia with Hgb < 10 g/dL B - Bone involvement with lytic lesions or osteoporosis Solitary plasmacytoma of bone Single plasmacytoma (biopsy proven), no plasma cells in bone marrow and no end organ damageIMWG = International Myeloma Working Group; MGUS = monoclonal gammopathy of undetermined significance.IMWG, 2009; Kyle et al, 2009; Rajkumar, 2011.
  19. 19. International Staging System (ISS) Stage Criteria Median Survival (months) I Serum β2m < 3.5 mg/L 62 Serum albumin ≥ 3.5 g/dL II Neither stage I nor III 44 III Serum β2m ≥ 5.5 mg/L 29Greipp et al, 2005.
  20. 20. The Durie and Salmon Staging System Stage I Stage II Stage III Low Cell Mass Intermediate Cell Mass High Cell Mass, Subclass A or B All of the Following: Fitting Neither Stage I 1 or More of the Following: • Hgb value > 10 g/dL nor Stage III • Hgb value < 8.5 g/dL • Serum calcium value • Serum calcium value > 12 mg/dL normal or < 10.5 mg/dL • Advanced lytic bone lesions (scale 3) • Bone X ray, normal • High M component production rates bone structure (scale 0), IgG value > 7 g/dL IgA value > 5 or solitary bone g/dL plasmacytoma only • Bence-Jones protein > 12 g/24 hours • Low M component production rates: IgG • A: Relatively normal renal function value < 5 g/dL; IgA (serum creatinine value) < 2.0 mg/dL value < 3 g/dL • B: Abnormal renal function (serum • Urine light chain M creatinine value) > 2.0 mg/dL component on Examples: Stage IA (low cell mass with electrophoresis (Bence- normal renal function) Stage IIIB (high Jones protein) cell mass with abnormal renal function) < 4 g/24 hoursDurie et al, 1975.
  21. 21. Key Takeaways MM is a malignant proliferation of a single clone of plasma cells that arise from B cells in the bone marrow Most patients present with bone pain and anemia Cytogenetic evaluation of the bone marrow is important for risk stratification and management of the disease The myeloma panel should be monitored closely to evaluate response to therapy or relapse disease Diagnosing MM at an early stage prevents organ damage such as renal failure and fractures
  22. 22. The Evolving Landscape ofMyeloma Treatment: First-Line Page Bertolotti, BSN, RN, OCN® The Samuel Oschin Cancer Center at Cedars-Sinai Medical Center
  23. 23. Case Study  60-year-old man  July: Chest pain, dyspnea. A stent was placed for coronary artery disease. Placed on an antiplatelet agent.  August: Developed hematuria and proteinuria. Treated for UTI.  November: Severe mid and lower back pain without trauma. Fatigue “no better since stent.” UA/C&S: 2+ proteinuria, hematuria; no bacteria.  UPEP: Immunofixation positive for kappa light chainsUTI = urinary tract infection; UA = urinalysis; C&S = culture & sensitivity.
  24. 24. Case Study: Baseline CBC and Chemistry WBC  Sodium, Whole Blood 3.70–11.00 k/uL 15.80 (H) 135–146 mmol/L 131 (L) RBC  Potassium, Whole Blood 4.20–6.00 m/uL 3.79 (L) 3.5–5.0 mmol/L 5.1 (H) Hgb  Chloride, Whole Blood 13.0–17.0 g/dL 7.7(L) 98–110 mmol/L 101 Hematocrit 21.2 (L)  Glucose, Whole Blood 65–100 mg/dL 260 (H) Platelets 150–400 k/uL 262  BUN, Whole Blood (iSTAT) 10–25 mg/dL 37 (H) Neut % 39.5%–74.0% 93.0 (H)  Creatinine, Whole Blood (iSTAT) 0.70–1.40 mg/dL 3.1 (H) ANC 1.45–7.50 k/uL 14.80 (H)  Calcium 8.5–10.5 mg/dL 14.3 Lymph % 15.9–47.3% 5.3 (L)  Protein, Total 6.0–8.4 g/dL 6.4 Abs Lymph 1.00–4.00 k/uL 0.80 (L)  Albumin 3.5–5.0 g/dL 4.0 Liver Function Normal
  25. 25. Case Study: CRAB Criteria?  Related organ or tissue involvement (CRAB) – Calcium > 11.5 mg/dL, actual value: 14.3 mg/dL – Renal (creatinine > 2 mg/dL), actual value: 3.1 mg/dL – Anemia (Hgb < 10 g/dL or 2 g/dL below LLN), actual: 7.7 g/dL – Bone/skeletal survey: Diffuse abnormal appearance of the pelvis. 2 large lytic lesions right femur. Calvarial lesions.  Additional testing? Calvarium Femur – BMB cytogenetics, FISH – “Myeloma labs” (SPEP, UPEP, sFLC)LLN = lower limit of normal.
  26. 26. Case Study: Bone Marrow and MM Studies Bone marrow plasma cell infiltration: 20% Myeloma FISH panel: Not performed; Cytogenetics: 46,XY ISS stage: Albumin: 3.6 g/dL, β2m: 6.0 mg/L (III) Salmon Durie Stage: Stage III (Hgb < 8.5g/dL, Ca ≥ 12 mg/dL, ≥ 3 lytic bone lesions, total IgG > 7 g/dL, IgA > 5 g/dL, or Bence-Jones protein > 12 g/24 hrs) B (creatinine ≥ 2 mg/dL) Monoclonal proteins at diagnosis – Serum M spike: Negative – Serum kappa free light chains: 3014.0 mg/L – Urinary M protein: 2.81 g/24 hrs Diagnosis: Symptomatic MM kappa light chain type Does this patient require treatmennt for MM?
  27. 27. Considerations: Initial or Induction Therapy  Induction chemotherapy – Treatment given to “induce” a response  The ideal initial or induction therapy should – Rapidly and effectively control disease – Reverse disease-related complications – Decrease the risk of early death – Be easily tolerated with minimal/manageable toxicity – Not interfere with the ability to collect stem cells for transplantation (if a transplant candidate based on age, desire, health status)Kumar et al, 2009.
  28. 28. Should All Patients Receive Induction Chemotherapy? Spectrum of Plasma Cell Dyscrasias Low M component, no CRAB High M component, no CRAB CRAB MGUS Smoldering MM MM  Only patients with symptomatic MM (CRAB) require treatment  Evidence that patients with “smoldering” MM can benefit from early treatment with lenalidomide + dexamethasone – This should only be recommended in the context of a clinical trial  A percentage of patients with MGUS may never require treatment – Increased sFLC ratio, higher M protein may indicate a group more likely to progress to symptomatic MM  3 key agents given today: Bortezomib, lenalidomide, and thalidomide in combination with corticosteroidsMateos et al, 2011; Khoriaty et al, 2010; Rajkumar et al, 2005.
  29. 29. Initial or Induction Therapy for MM: Transplant Eligible and Ineligible Transplant Ineligible Transplant Eligible Melphalan +/- Induction Therapy • Bortezomib Non-Alkylator Based • Lenalidomide • Thalidomide • Other Early Delayed Autologous Autologous Transplant Transplant  Supportive care should be considered at diagnosis and throughoutNCCN, 2012; Kumar et al, 2009.
  30. 30. How Do You Treat MM: Specific Doses Transplant Candidate Bortezomib + Bortezomib 1.3 mg/m2 SC/IV Days 1, 4, 8, 11 + dexamethasone Dexamethasone 20 mg PO Day 1, 2, 4, 5, 8, 9, 11, 12 (+ cyclophosphamide, lenalidomide, or thalidomide) Lenalidomide + Lenalidomide 25 mg PO Days 1–21, q28d + dexamethasone Dexamethasone 40 mg PO wkly (+ bortezomib 1.3 mg/m2 wkly or BID?) (+/- bortezomib?) Thalidomide + Thalidomide 200 mg PO Days 1–28 + dexamethasone Dexamethasone 40 mg PO Days 1–4, 9–12, 17–20 x 4 28-day cycles (+ bortezomib or PLD?) (+ bortezomib or PLD?) – LESS COMMON TO GIVE THAL UPFRONT Non-Transplant Candidate Any of the novel agents Prednisone is often substituted for dexamethasone (elderly poor tolerance) Melphalan + any of MPV: 9 6-wk cycles of melphalan 9 mg/m2 PO + prednisone 60 mg/m2 PO Days 1–4 and/ the above or bortezomib 1.3 mg/m2 on Days 1, 4, 8, 11, 22, 25, 29, 32 during Cycles 1–4 and Days 1, 8, 22, 29 during Cycles 5–9 Maintenance May improve PFS; ongoing studiesPO = oral; MPV = melphalan, prednisone, bortezomib; PLD = pegylated liposomal doxorubicin; PFS = progression-free survival.NCCN, 2012; Rajkumar et al, 2007; San Miguel et al, 2008; Kumar et al, 2008; Ludwig et al, 2009; Jagannath et al, 2004;Thalomid® prescribing information, 2012.
  31. 31. Can Induction Therapy Be Individualized? The Mayo Clinic Approach Approx. 25% of patients Approx. 75% of patients mSMART 2.0: Classification of active MM Newly Diagnosed Myeloma Eligible for Transplantation High Risk Standard Risk High Risk Intermediate Standard Risk Risk 4–6 cycles of CyBorD or 4 cycles of Rd FISH FISH All other VRd including: del(17p) t(4;14) Collect Stem Cells Collect Stem Cells t(14;16) Cytogenetic Hyperdiploidy del(13) or t(14;20) Autologous stem cell Autologous Continue hypodiploidy t(11;14) transplant stem cell OR Rd GEP PCLI ≥ 3% t(6;14) transplant • High-risk Bortezomib-based signature maintenance Consider Lenalidomide maintenance Newly Diagnosed Myeloma Not Eligible for Transplantation High Risk Standard Risk VMP or CyBorD RdRd = lenalidomide, dexamethasone; VRd = bortezomib plus Rd; CyBorD = cyclophosphamide, bortezomib, dexamethasone;VMP = bortezomib, melphalan, prednisone.Dispenzieri-Kumar, 2011.
  32. 32. Side Effects of Common Therapies: Snapshot Oral Thalidomide Oral Lenalidomide IV/SC Bortezomib PN √ √ DVT √ √ Myelosuppression √ √ √ Neutropenia Neutropenia, Thrombocytopenia thrombocytopenia, anemia Hypotension √ Fatigue, weakness √ √ √ Sedation √ Rash √ √ GI disturbance √ √ √ Constipation Constipation, diarrhea Nausea and vomiting, diarrhea Dose modifications to address side effects can optimize adherence, allow patients to remain on regimen longer!DVT = deep vein thrombosisThalomid® prescribing information, 2012; Velcade® prescribing information, 2012;Revlimid® prescribing information, 2011; Palumbo et al, 2011.
  33. 33. Important Considerations in MM: Bone Disease  Malignant cells produce osteoclast-activating factors (hormones, cytokines) that destroy bone cells – Leads to osteolysis, bone pain, and pathologic fracture  BP (pamidronate, zoledronic acid) inhibit bone destruction – Monitor patients for • Acute phase reactions (flulike sxs, chills) • Renal dysfunction – Dose reduce BP for decreased CrCl, longer infusion time – Monitor for albuminuria, a sign of tubular damage • Osteonecrosis of the jaw (ONJ) – Baseline and ongoing dental exams – Hold BP if jaw painBP = bisphosphonates; CrCl = creatinine clearance; ONJ = osteonecrosis of the jaw.Tariman et al, 2010; Kyle et al, 2007; Morgan et al, 2010a.
  34. 34. Important Considerations in MM: Infections  A leading cause of death in myeloma patients  Ig levels decreased (hypogammaglobulinemia)  Infiltration of bone marrow by plasma cells  Cytotoxic therapy, transplant and glucocorticoids  Interventions – Prompt reporting of symptoms – Intravenous immunoglobulin (IVIG) prophylaxis for frequent infections – Poor response to pneumococcal and influenza vaccines – Herpes zoster oral prophylaxis (bortezomib)Barlogie et al, 2006; Durie at al, 2003; Malpas et al, 2004; NCCN, 2012.
  35. 35. Important Considerations in MM: Peripheral Neuropathy  Damage to the peripheral nervous system caused by injury, inflammation, or degeneration of peripheral nerve fibers (sensory, motor, autonomic)  Incidence of CIPN is increasing – More neurotoxic drugs have been developed, patients are living longer  Thalidomide and bortezomib (vincristine, cisplatin less commonly used)  Sensory, motor, autonomic  Signs and symptoms: Numbness, tingling, pain  Monitoring: Symptom assessment, test sensation, DTRs, gait, proprioception Grade 1 Grade 2 Grade 3 Grade 4 Peripheral Sensory Asymptomatic; loss Moderate symptoms; Severe symptoms; Life-threatening; Neuropathy of reflexes limiting instrumental limiting selfcare urgent intervention ADLs ADLs indicated If pain: Reduce 1 level or change to Hold and/or reduce wkly STOPADLs = activities of daily life; CIPN = chemotherapy-induced peripheral neuropathy; DTR = deep tendon reflexes.Tariman et al, 2008; Wickham, 2007; Thalomid® prescribing information, 2012; Velcade® prescribing information, 2012;NCI.v4.0 (CT-CAE), 2009; Richardson et al, 2011.
  36. 36. Venous Thromboembolic Events (VTEs) in MM  MM is an intrinsically hypercoagulable disease associated with a higher risk of thromboembolic events  Higher risk for DVT/PE in patients treated with conventional chemotherapies plus novel therapies (thalidomide, lenalidomide) – Prior VTEs, surgery, immobility, obesity require LMWH/warfarin – All patients should receive ASA unless contraindicated  Dx: Duplex ultrasound, spiral CT if PE suspected  Prevent: Ambulate, SCDs, antiembolism stockings (questionable benefit), exercise  Prophylaxis if high risk as abovePE = pulmonary embolism; SCD = sequential compression device; LMWH = low molecular weight heparin;ASA = acetylsalicylic acid.Rome et al, 2008; Musallam et al, 2010; Menon et al, 2008.
  37. 37. Side-Effect Assessment and Management Individualized for Each Patient What is the risk of VTE? Increased if prior VTE, receiving IMiDs, etc. Bone health Are bisphosphonates indicated? Infectious diseases Is your patient at high risk for – Wkly CBC, differential for infection? 8 wks with lenalidomide (myelosuppression from – Acyclovir prophylaxis with disease/treatment) bortezomib – IV Ig for recurrent infections (a result of hypogammaglobulinemia) GI Antiemetic prior to bortezomib, Assess for diarrhea, doxorubicin constipation PN Review increased risk of PN with Prompt intervention can bortezomib and thalidomide prevent irreversible PN symptoms Monthly monitoring of SPEP, UPEP, 24-hr urine, sFLC disease parametersIMiDs = immunomodulatory drugs.IMF, 2011; Kyle et al, 2007; NCCN, 2012; Smith et al, 2008.
  38. 38. Bortezomib: New Data on Survival, Dosing  VISTA trial: 655 patients VMP (mos) MP (mos) ineligible for transplant Median OS 56.4 43.1  US, transplant eligibility – Age, desire, social, financial Median time 27 19.2 to next  Patients randomized to 9 6-wk treatment cycles of MP plus bortezomib (VMP) or to MP alone Wkly bortezomib: Significantly less severe PN (3%)  New evidence for dosing of compared with twice-wkly IV without a change in bortezomib – Once-wkly IV response – SC Bortezomib SC is not inferior to IV by overall response rateMP = melphalan, prednisone; OS = overall survival; TTP = time to progression. Bortezomib SC not different from IV bySan Miguel et al, 2011; Moreau et al, 2011.
  39. 39. Lenalidomide: New Data on Safety, Efficacy  Similar to bortezomib, oral lenalidomide remains a common treatment for patients with newly diagnosed MM (transplant eligible or ineligible)  Tumoricidal and immunomodulatory  Non-transplant: MPR-R vs. MPR vs. MP – Continuous MPR-R reduced risk of progression, maintenance improved PFS 31 mos  Lenalidomide post-transplant maintenance improves PFS (compared to placebo)MPR = melphalan, prednisone, lenalidomide; MPR-R = MPR plus lenalidomide maintenance.Palumbo et al, 2010, 2011; McCarthy et al, 2011; Attal et al, 2011.
  40. 40. Is My Patient Responding to Treatment? Response Assessment* Response IMWG Response IMWG sCR CR as below plus normal FLC ratio PD Increase of ≥ 25% from + absence of clonal cells in bone lowest response value: marrow by IHC Serum ≥ 0.5 g/dL; CR Neg IFE on the serum + urine, Urine ≥ 200 mg/24 hrs; disappearance of any soft tissue Bone marrow plasma cell plasmacytomas and < 5% BM PCs (BMPCs) ≥ 10% VGPR Serum and urine M protein Relapse See above and/or CRAB detectable by IFE but not on electrophoresis or ≥ 90% reduction in serum M protein + urine M protein level < 100 mg/24 hrs *Note: This is not inclusive PR Serum and urine M protein of all response categories. detectable by immunofixation but not on electrophoresis or ≥ 50% reduction in serum M proteinIHC = immunohistochemistry; CR = complete response; sCR = stringent CR; PR = partial response;VGPR = very good partial response; PD = progression disease.Durie et al, 2006; Kyle et al, 2008
  41. 41. Case Study (cont.) Remember our case study? Does not want to pursue up-front transplant Induction regimen (clinical trial) – Bortezomib 1.3 mg/m2 IV Day 1, 4, 8, 11 q21days – Dexamethasone 40 mg Day 1, 2, 4, 5, 8, 9, 11, 12 q21days – Cyclophosphamide 500 mg absolute po on Day 1, 8, 15 q28days Side effects – Mild PN after Cycle 3 (discomfort feet) – Mild steroid induced hyperglycemia, managed with diet, glipizide Decided to withdraw consent for clinical trial
  42. 42. Case Study (cont.)  After Cycle 5, he was changed to KAPPA, FREE, SERUM K/L RATIO, Mo/Ref Rng 3.3 - 19.4 mg/L 0.26 - 1.65 bortezomib SC (reconstitute at 2.5 January 3014.0 (H) >1255.83 (H) mg/mL NS and rotate injection sites) February 911.9 (H) >379.96 (H) based on new data March 939.4 (H) 391.42 (H) April 550.0 (H) 110.00 (H)  After 8 cycles: Continues on May 419.1 (H) 83.82 (H) Sept* 93.7 (H) >39.04 (H) bortezomib Days 1, 8, 15, 22 November 5.8 (H) >23.25 (H) q28days; neuropathy has improved January 7.4 1.48 from Grade 2 to Grade 1 PN with pain February 5.4 1.08  Switched from cyclophosphamide to Component M Spike Quant 24 Hr lenalidomide 5 mg Days 1–21 in Mo/ Ref Rng Low: 0.00 gm/24 Hr January 1.391 September to deepen response March 1)0.074 2)0.215 April 0.193  Now has achieved a complete Sept <0.093 remission which remains sustained November 0.134 January 0.00 No M Spike Detected February 0.00 No M Spike DetectedNS = normal saline.
  43. 43. Case Study: Question 1You are the nurse caring for this patient. Recall his baselinelaboratory studies. He has anemia, renal insufficiency,hypercalcemia, and lesions on his bone survey. He will startCycle 1 of treatment.What supportive care therapy would you consider to beimportant? 1) Granulocyte stimulating factor (GCSF) 2) Platelet transfusions 3) Bone marrow transplant 4) Bisphosphonates, acyclovir 5) None of the above
  44. 44. Key Takeaways There is no‘gold standard’treatment for MM Newer agents provide improved response rates, improved survival Nurses play an important role in side-effect recognition, management Newer dosing strategies can decrease side effects Personalized care plans are necessary for all patients
  45. 45. The Evolving Landscape of Myeloma Treatment: Maintenance Therapy Beth Faiman, PhD(c), MSN, APRN, BC, AOCN® Cleveland Clinic Taussig Cancer Institute
  46. 46. Case Study: Maintenance  Mr. P is a 48-year-old with newly diagnosed IgG Kappa multiple myeloma  M spike at diagnosis: 5.2 g/dL  CRAB features at presentation – Renal insufficiency (creatinine 2.8 mg/dL) – Anemia (Hgb 8.8 g/dL)  Receives 4 cycles of induction chemotherapy with bortezomib and dexamethasone and undergoes ASCT  Would he be a candidate for maintenance therapy?ASCT = autologous stem cell transplant.
  47. 47. Maintenance Therapy Maintenance therapy is the use of ongoing low intensity chemotherapy to eliminate or suppress the minimal residual tumor clone over a prolonged period of time Maintenance therapy is administered when the disease is in remission, either undetectable or at a low level The purpose of maintenance therapy is to prolong remission duration and thereby, life expectancy Immunomodulatory molecules are well suited for maintenance therapy, as they can be administered orally at low doses for a prolonged period of time
  48. 48. Thalidomide Maintenance After ASCT Author/Year N Thalidomide Dose (mg) PFS / OS / Duration EFS Attal et al, 2006 597 Thalidomide 200 (median dose) + + vs. observation / progression Spencer et al, 2006 243 Thalidomide 200 + prednisone + + vs. prednisone / 12 months Maiolino et al, 2008 212 Thalidomide 200 + dexamethasone + NS vs. dexamethasone / 12 months Barlogie et al, 2006* 668 Thalidomide 400 / progression + NS (+ in high-risk) Morgan et al, 2010a* 820 Thalidomide 100 / progression +/- NS (if optimal relapse Rx) Lokhorst et al, 2010* 550 Thalidomide 50 / progression + - Stewart et al, 2010 332 Thalidomide 200 + prednisone + NS vs. observation / 48 months*Thalidomide also given as part of induction therapy.PFS = progression-free survival; EFS = event-free survival; OS = overall survival; NS = not significant.
  49. 49. Thalidomide Maintenance: MRC Trial At Median Follow-Up From Randomization of 38 Months 100 100 Maintenance, N = 407 No maintenance, N = 410 80 80 HR [95% CI] = 1.45 [1.22, 1.73], p = .0003Patients (%) Patients (%) 60 60 40 40 Maintenance, N = 408 No maintenance, N = 410 20 20 HR [95% CI] = 0.91 [0.72, 1.17], p = 0.40 0 12 24 36 48 60 72 0 12 24 36 48 60 72 PFS (months) OS (months)  Thalidomide maintenance improves PFS with no OS advantageHR = hazard ratio; CI = confidence interval.Morgan et al, 2010b.
  50. 50. Lenalidomide Maintenance: CALGB 100104 Schema CALGB, ECOG, BMT-CTN Registration Restaging Randomization Days 90–100 Placebo D-S Stage 1-3, ≤ 70 years ≥ 2 cycles of induction Mel 200 CR Attained SD or better PR Lenalidomide* ≤ 1 yr from start of therapy ASCT ≥ 2 x 106 CD34 cells/kg SD 10 mg/d with ↑↓ (5–15 mg) Patient stratification based on diagnostic β2m level and prior thalidomide and lenalidomide use during inductionCALGB = Cancer and Leukemia Group B; ECOG = Eastern Cooperative Oncology Group; BMT-CTN = Blood andMarrow Transplant-Clinical Trials Network; CR = complete response; PR = partial response; SD = stable disease;β2m = beta-2-microglobulin.McCarthy et al, 2011.
  51. 51. PFS and OS at Median Follow-Up of 34 Months Median TTP: 46 mos Median TTP: 27 mos p = .027 p < .0001  Survival at 3 years is 88% for the lenalidomide and 80% CALGB 100104, for placebo arm patients, HR = 0.62 (95%CI = 0.40–0.95) Follow-Up 10/31/11  35 deaths in the lenalidomide arm and 53 deaths in the placebo armTTP = time to progression.McCarthy et al, 2011.
  52. 52. Lenalidomide Maintenance Post- Transplant: IFM 2005-02: Placebo-Controlled Trial Phase III Randomized, Study Design N = 614 Patients, From 78 Centers, Enrolled Between 7/2006 and 8/2008 Patients < 65 Years, With Non-Progressive Disease, ≤ 6 Months After ASCT in First-Line Randomization: Stratified According to β2m, del(13), VGPR Consolidation: Lenalidomide alone 25 mg/day po Days 1–21 q28days for 2 months Arm A Arm B Placebo Lenalidomide (n = 307) (n = 307) until relapse 10–15 mg/d until relapse  Primary end point: PFS  Secondary end points: CR rate, TTP, OS, feasibility of long-term lenalidomideIFM = Intergroupe Francophone du Myelome; del(13) = deletion 13; VGPR = very good partial response;Attal et al, 2011.
  53. 53. Lenalidomide Maintenance Post-Transplant: IFM 2005-02: PFS and OS From Randomization (4/2011) Median F/U: 36 months post-random, 46 months post-diagnosis PFS OS 1.00 1.00 Rev (n = 307) p = .79 0.75 0.75 0.50 0.50 p < 10 -9 0.25 0.25 Placebo (n = 307) 0.00 0.00 0 6 12 18 24 30 36 42 48 54 0 6 12 18 24 30 36 42 48 Placebo Lenalidomide Revlimid Placebo Lenalidomide RevlimidAttal et al, 2011.
  54. 54. MM-015: Study Design N = 459, 82 centers in Europe, Australia, and Israel Open-Label Double- Blind Treatment Phase Extension Phase Cycles (28-day) 1-9 Cycles 10+ MPR-R RANDOMIZATION M: 0.18 mg/kg, days 1-4 Maintenance P: 2 mg/kg, days 1-4 Lenalidomide R: 10 mg/day po, days 1-21 10 mg/day days 1-21 MPR Lenalidomide M: 0.18 mg/kg, days 1-4 Disease (25 mg/day) P: 2 mg/kg, days 1-4 Placebo Progression +/- R: 10 mg/day po, days 1-21 Dexamethasone MP M: 0.18 mg/kg, days 1-4 P: 2 mg/kg, days 1-4 Placebo PBO: days 1-21  Stratified by age (< 75 vs. > 75 years) and stage (ISS I/II vs. III)  Primary comparison: MPR-R vs. MPPalumbo et al, 2011b.
  55. 55. MM-015: PFS and OS for Survival Progression-Free and Overall All Patients All Patients Median PFS 4-year OS MPR-R 31 months MPR-R 59% MPR 14 months MPR 58% 100 MP 13 months 100 MP 58% 75 HR 0.898 75 P = .579 Patients (%) Patients (%) 50 HR 0.395 50 P < .001 HR 1.089 P = .648 25 HR 0.796 25 P = .135 0 0 0 10 20 30 40 0 10 20 30 40 50 60 Time (Months) Time (Months) TTP HRHR advantages were similar: MPR-R vsMP = 0.337; MPR vs MP = 0.826 • TTP advantages were similar: MPR-R vs. MP = 0.337; MPR vs. MP = 0.826 HR, hazard ratio; MP, melphalan, prednisone; MPR, melphalan, prednisone, lenalidomide; MPR-R, melphalan, prednisone, lenalidomide with lenalidomide maintenance; OS, overall survival; PFS, progression-free survival; TTP, time to progression.MP = melphalan; P = prednisone; R = lenalidomide.Palumbo et al, 2011b.
  56. 56. HOVON Trial: Bortezomib Induction and Maintenance Randomization Bortezomib 1.3 mg/m2 Doxorubicin 9 mg/m2 3 x VAD 3 x PAD Dexameth 40 mg CAD + GCSF CAD + GCSF Mel 200 + PBSCT Mel 200 + PBSCT In GMMG 2nd Allogeneic In GMMG 2nd Mel 200 + PBSCT Mel 200 + PBSCT Tx Thalidomide Bortezomib maintenance Maintenance 50 mg/day for 1.3 mg/m2 / 2 weeks 2 years for 2 yearsCAD = coronary artery disease; GCSF = granulocyte colony-stimulating factor; PBSCT = peripheral blood stem cell transplant.Sonneveld et al, 2010.
  57. 57. Bortezomib Maintenance: Outcomes 3-year PFS 48% vs. 42% 3-year OS 78% vs. 71% Progression free survival Overall survival 100 100 B: PAD 75 p = .005 75 Cumulative percentage Cumulative percentage p = .02 A: VAD B: PAD 50 50 A: VAD 25 25 N F N D A: VAD 373 243 A: VAD 373 120 B: PAD 371 215 B: PAD 371 93 0 0 0 12 24 36 months 48 0 12 24 36 months 48 At risk: At risk: A: VAD 373 289 199 110 30 A: VAD 373 320 290 174 63 B: PAD 371 321 237 118 39 B: PAD 371 336 306 191 79 10 Nov 2010-15:14:3410 Nov 2010-15:14:01 VAD PAD CR/nCR 34 49 < .001 ≥ VGPR 55 76 .001 ≥ PR 83 91 .003 nCR = near complete response. Sonneveld et al, 2010.
  58. 58. Subgroup Analysis (1) VAD/HDM/ PAD/HDM/ Thalidomide Bortezomib N PFS at OS at N PFS at OS at 36 mos 36 mos 36 mos 36 mos (%) (%) (%) (%) All 373 40 70 371 48 78 ISS 1 168 50 81 167 55 86 ISS 2 65 32 70 93 45 71 ISS 3 101 29 50 73 37 68 Creatinine 0–2 mg/dL 328 44 75 336 48 78 > 2 mg/dL 44 12 32 34 49 72 p < .01 in univariate analysisISS = International Staging System.Sonneveld et al, 2010.
  59. 59. Subgroup Analysis (2) VAD/HDM/ PAD/HDM/ Thalidomide Bortezomib N PFS at OS at N PFS at OS at 36 mos 36 mos 36 mos 36 mos (%) (%) (%) (%) All 373 40 70 371 48 78 -13/13q- 155 29 58 134 40 79 t(4;14) 33 20 40 31 28 60 17p- 39 16 17 19 22 61 p < .01 in univariate analysis All data FISH, -13/13q- also karyotype if availableFISH = fluorescent in situ hybridization.Sonneveld et al, 2010.
  60. 60. Case Study: Maintenance Conclusion 3 months following ASCT, Mr. P achieved a PR (80% reduction in serum m protein) – M spike 0.49 g/dL Renal insufficiency and anemia resolved – Creatinine normal 0.8 g/dL – Hbg 13.4 g/dL Would he be a candidate for maintenance therapy? ANSWER: Yes (based on data presented) Began maintenance with lenalidomide 10 mg po daily
  61. 61. Key Takeaways Maintenance therapy delays recurrence of myeloma and prolongs PFS Chronic low dose oral agents are preferable for maintenance strategy Bortezomib and lenalidomide are better suited for high-risk disease There is a slight increase in incidence of second malignancy after lenalidomide maintenance following melphalan New agents may be appropriate for maintenance studies – Carfilzomib, pomalidomide, oral proteasome inhibitors (MLN9708, ONX0912)
  62. 62. The Evolving Landscape of Myeloma Treatment:Relapsed/Refractory Disease Beth Faiman, PhD(c), MSN, APRN, BC, AOCN® Cleveland Clinic Taussig Cancer Institute
  63. 63. Case Study: Mr. P (cont.) Mr. P remains on lenalidomide 10 mg po daily for 3 years Develops lower back pain and worsening anemia Bone survey – L2 vertebral compression fracture and calvarial lesions consistent with disease progression Labs – M spike February 2012: 0.95 g/dL – M spike March 2012: 1.32 g/dL (confirms disease progression) – Hgb 9.2 g/dL, creatinine 1.3 mg/dL Mr. P has relapsed myeloma What are his treatment options?
  64. 64. How Is Relapse Defined?  Relapse is defined as reappearance of signs and symptoms of the disease or signs of increasing disease and/or end organ dysfunction (MDE) that are felt related to the underlying myeloma 1) Reappearance or increase in paraprotein serum and/or urine – serum M spike, sFLC or BJP in urine 2) Development of new soft tissue plasmacytomas or bone lesions or increase in the size of existing lesion on imaging 3) Hypercalcemia 4) Development of anemia 5) New or worsening kidney function 6) Hyperviscosity requiring therapeutic interventionMDE = myeloma-defining event; sFLC = serum free light chain; BJP = Bence Jones protein.Lonial, 2010; Bird et al, 2011; Anderson et al, 2008.
  65. 65. When Do You Treat Relapsed Myeloma?  Symptomatic relapse – CRAB symptoms: HyperCalcemia, Renal impairment, Anemia, Bone lesion, new plasmacytoma, bone lesions  Clinically significant relapse – Doubling of paraprotein • (M spike > 1 g/dL, BJP > 500 mg/day, sFLC level > 200 mg/L)  Asymptomatic biochemical relapse should not be treated  Goals: Control of disease, decrease morbidity  Nurses can ensure ongoing evaluation for risk of VTE, skeletal events, infections, neuropathyBird et al, 2011; Anderson et al, 2008.
  66. 66. How Is Refractory Disease Defined?  Refractory disease should fulfill all of the following criteria – Should have failed > 2 lines of therapy – Should have PD after treatment with all 4 classes of drugs • Cytotoxic agents (melphalan, cyclophosphamide, anthracyclines, bendamustine) • Immunomodulatory agents (thalidomide, lenalidomide) • Proteasome inhibitor (bortezomib) • Glucocorticoids (prednisone, dexamethasone) – Should be progressing on the last line of therapy or within 60 days of discontinuing treatmentPD = progressive disease.Lonial, 2010; Anderson et al, 2008.
  67. 67. Considerations in Relapsed MM  Disease related – Indolent, slow, or single site relapse – Rapid and multiple sites of relapse – Extramedullary disease, CNS, plasma cell leukemia – Additional genetic changes  Patient related – Poor performance – Poor renal function – Poor hematopoietic reserve  Treatment related – Prior drug exposure (relapsed or PD on therapy) – Ongoing toxicity from prior therapyCNS = central nervous system.Mohty et al, 2012; Richardson et al, 2010; Lonial, 2010.
  68. 68. Treatment of Relapsed Myeloma: How Do We Decide?  Existing novel agents – Thalidomide, bortezomib, lenalidomide  Existing older agents – Dexamethasone, prednisone, cyclophosphamide, melphalan, anthracyclines  Clinical trial options  Single agent vs. combinationNCCN, 2012; Laubach et al, 2009; Blade et al, 2009.
  69. 69. Indolent, Slow, or First Relapse High-Dose Melphalan and Stem Cell Transplant If Deferred During First-Line of Therapy Lenalidomide Bortezomib Thalidomide Based Salvage Based Salvage Based Salvage  Initial Tx with Bz  Initial Tx with IMiD  Prior  Renal dysfunction bortezomib/lenalid  Underlying PN  High-risk genetics; omide  Good risk 1q+, del(17p), t(4;14)  Cytopenia  Severe renal impairment Clinical Trial OptionsTx = therapy; Bz = bortezomib; PN = peripheral neuropathy; IMiD = immunomodulatory drugs.Lonial et al, 2011.
  70. 70. Aggressive, Rapid, Multiple Relapse Likely Combination Therapy Do Not Wait for Symptomatic Relapse Chemotherapy Chemotherapy + Transplant Based Salvage Novel Agent Based Salvage  DCEP vs. DT-PACE  Combinations of  Additional stem cells Len/Bz and other in storage chemo agents  Long remission after first transplant  Cytopenia Clinical Trial OptionsDCEP vs. DT-PACE = dexamethasone/cyclophosphamide/etoposide/cisplatin vs.dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophos/phanide/etoposide; Len = lenalidomide.Lonial et al, 2011.
  71. 71. Agents in Phase III Studies Target Combination Partner(s) Pomalidomide Dexamethasone Carfilzomib Lenalidomide, Dexamethsone Vorinostat Bortezomib Panobinostat Bortezomib Elotuzumab Lenalidomide, Dexamethsone Perifosine BortezomibCourtesy of US NIH, 2012.
  72. 72. Molecular Structure of Thalidomide, Lenalidomide, and Pomalidomide  Structurally similar, but functionally different both qualitatively and quantitativelyDVT = deep vein thrombosis.Kotla et al, 2009; Thalomid® prescribing information, 2010; Revlimid® prescribing information, 2010.
  73. 73. Relapsed and Refractory Myeloma Single Agent: Pomalidomide POM POM + LoDEX (n = 108) (n = 113) ORR (≥ PR) % 13 34 ≥ MR % 29 45 CR % 1 1 PR % 12 33 VGPR % 2 9 MR % 16 12 SD % 50 37 PD % 10 6 NE % 11 12 Median time to response, months 2.9 1.9 Median DOR, months 8.5 7.9 Discrepancies in totals are due to rounding.  Disease control (≥ SD) observed in 81% of overall patientsPOM = pomalidomide; ORR = overall response rate; PR = partial response; MR = minor response;CR = complete response; VGPR = very good partial response; SD = stable disease; NE = non-event;DOR = duration of response.Richardson et al, 2011.
  74. 74. Relapsed and Refractory Myeloma Single Agent: Pomalidomide (cont.) 100 100 POM + LoDEX POM + LoDEX 80 POM 80 POMPatients (%) Patients (%) 60 60 40 40 20 20 0 0 0 5 10 15 20 0 5 10 15 20 PFS (months) OS (months)  Median PFS: POM + LoDEX 4.7 months; POM alone 2.7 months  Median OS: POM + LoDEX 16.9 months; POM alone 14 months ~ Median OS for patients with PD as best response; 5.4 monthsPFS = progression-free survival; OS = overall survival.Richardson et al, 2011.
  75. 75. Relapsed and Refractory Myeloma Single Agent: Carfilzomib PX171-003 A1 ORR CBR DOR All patients (N = 257) 24 34 8.3 PD on or within 60 days (N = 227) 24 34 8.3 Proportion of Patients Surviving Proportion of Patients Without Progression Months Since Study Entry Months Since Study Entry Median PFS: 3.7 months Median OS: 15.5 monthsCBR = clinical benefit response; ORR = overall response rate.Siegel, Martin, et al, 2010.
  76. 76. Vantage 095: PFS (IAC) BTZ + BTZ + Vorinostat Placebo Events 201/317 216/320 100 Median PFS 7.63 months 6.83 months 90 (95% CI) (6.9–8.4) (5.7–7.7) 80 HR (95% CI) 0.774 (0.64–0.94) 70 p Value 0.01 60 VGPR 28 21 PFS (%) 50 PR 28 19 ORR 56 41 40 30 20 BTZ + Vorinostat 10 BTZ + Placebo 0 0 5 10 15 20 25 Time (months)IAC = independent adjudication committee; CI = confidence interval; HR = hazard ratio.Siegel et al, 2011.
  77. 77. Elotuzumab With Lenalidomide and Weekly Dexamethasone Best Response (IMWG Criteria) Elotuzumab Elotuzumab 10 mg/kg 20 mg/kg Total Patients, n 36 37 73 ORR (≥ PR), n (%) 33 (92) 27 (73) 60 (82) CR/stringent CR, n (%) 5 (14) 4 (11) 9 (12) VGPR, n (%) 14 (39) 12 (32) 26 (36) PR, n (%) 14 (39) 11 (30) 25 (34) < PR, n (%) 3 (8) 10 (27) 13 (18)  At a median follow-up of 14.1 months, the median PFS was not reachedIMWG = International Myeloma Working Group.Lonial et al, 2011.
  78. 78. Phase I/II Trial of Perifosine/Bortezomib ± Dexamethasone in Relapsed/Refractory Myeloma (N = 73) Median No. of Treatment Cycles Received: 8  Median prior Rx in Bz refractory patients: 6  Median prior Rx in Bz relapsed patients: 4  Median prior Bz in Bz refractory patients: 2  Median prior Bz in Bz relapsed patients: 1  45/84 patients (54%) had Dex added to Peri/Vel  39/84 (46%) patients had Peri/Vel onlyMR = minimal response; Bz = bortezomib.Richardson et al, 2011.
  79. 79. Case Study (cont.) Mr. P is enrolled in a clinical trial with Lenalidomide, Elotuzumab and Dexamethasone He achieves a VGPR (> 90% reduction in serum M-protein) after 3 months of therapy Side effects of myelosuppression were mild and controlled with appropriate dose adjustments He continues on therapy per clinical trial protocol until relapse
  80. 80. Key Takeaways The overall survival of patients with MM has increased within the last decade Many new treatments have become available The diagnosis of MM has transitioned to a chronic disease thus supportive care must be ongoing Future research is directed at newer targets using a more “novel” approach
  81. 81. Patient Perspective Pat KillingsworthColumnist for the Myeloma Beacon
  82. 82. Oncology Nurses Rock!A Long, 5-Year Rollercoaster Ride How to Help Newly DiagnosedPatients Cope: Take a TIME-OUT!
  83. 83. Ignore Median Expectancy NumbersHelp Patients Build A Healthcare Team Don’t Rush to Transplant – Do Your Homework First
  84. 84. Multiple Myeloma Patient ResourcesInternational Myeloma Foundation (IMF) - www.myeloma.org The Myeloma Beacon – www.myelomabeacon.com www.multiplemyelomablog.com www.mymultiplemyeloma.com Books by Pat Killingsworth Living with Multiple Myeloma Stem Cell Transplants from a Patient’s Perspective Found on: www.multiplemyelomablog.com

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