Based on the patient's presentation and laboratory results, what is the most likely diagnosis?

2. DISCLAIMER
This slide deck in its original and unaltered format is for educational purposes and is
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materials may discuss therapeutic products that have not been approved by the US
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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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3. 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 of
agents 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 for
each product for discussion of approved indications, contraindications, and warnings.

4. 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.

5. Activity Overview
Beth Faiman, PhD(c), RN, APRN, BC, AOCN®
Cleveland Clinic Taussig Cancer Institute

6. 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

7. 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

8. 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

9. Diagnosing Multiple Myeloma
Page Bertolotti, BSN, RN, OCN®
The Samuel Oschin Cancer Center
at Cedars-Sinai Medical Center

10. 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 impairment
Kyle et al, 2009; Nau et al, 2008.

11. 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, fatigue
Hgb = hemoglobin.
Dispenzieri et al, 2009; Nau et al, 2008; Rajkumar, 2011.

12. 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.

13. 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
erythematosus
Kyle et al, 2012; Rajkumar, 2011; Tariman, 2010; Okali et al, 2009.

14. 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
 Imaging
BMB = bone marrow biopsy; FISH = fluorescent in situ hybridization; PCLI = plasma cell labeling index.
Kyle et al, 2012; Dispenzieri et al, 2009; NCCN, 2012.

15. 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 signature
mSMART = Mayo Stratification of Myeloma and Risk-Adapted Therapy; GEP = gene-expression profiling.
Dispenzieri-Kumar et al, 2011.

16. 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 burden
CBC = complete blood count; LDH = lactate dehydrogenase; β2m = beta-2-microglobulin.
Kyle et al, 2012; Tariman et al, 2010; Dispenzieri et al, 2009.

17. 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 impairment
SPEP = 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.

18. 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 disease
MRI = magnetic resonance imaging; PET = positron emission tomography; R/O = rule out.
Kyle et al, 2012; Dispenzieri et al, 2009; Durie, 2011.

19. 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 damage
IMWG = International Myeloma Working Group; MGUS = monoclonal gammopathy of undetermined significance.
IMWG, 2009; Kyle et al, 2009; Rajkumar, 2011.

20. 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 29
Greipp et al, 2005.

21. 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 hours
Durie et al, 1975.

22. 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

23. The Evolving Landscape of
Myeloma Treatment: First-Line
Page Bertolotti, BSN, RN, OCN®
The Samuel Oschin Cancer Center
at Cedars-Sinai Medical Center

24. 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 chains
UTI = urinary tract infection; UA = urinalysis; C&S = culture & sensitivity.

25. 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

26. 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.

27. 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?

28. 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.

29. 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 corticosteroids
Mateos et al, 2011; Khoriaty et al, 2010; Rajkumar et al, 2005.

30. 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 throughout
NCCN, 2012; Kumar et al, 2009.

31. 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 studies
PO = 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.

32. 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 Rd
Rd = lenalidomide, dexamethasone; VRd = bortezomib plus Rd; CyBorD = cyclophosphamide, bortezomib, dexamethasone;
VMP = bortezomib, melphalan, prednisone.
Dispenzieri-Kumar, 2011.

33. 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 thrombosis
Thalomid® prescribing information, 2012; Velcade® prescribing information, 2012;
Revlimid® prescribing information, 2011; Palumbo et al, 2011.

34. 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 pain
BP = bisphosphonates; CrCl = creatinine clearance; ONJ = osteonecrosis of the jaw.
Tariman et al, 2010; Kyle et al, 2007; Morgan et al, 2010a.

35. 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.

36. 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 STOP
ADLs = 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.

37. 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 above
PE = 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.

38. 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 parameters
IMiDs = immunomodulatory drugs.
IMF, 2011; Kyle et al, 2007; NCCN, 2012; Smith et al, 2008.

39. 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 rate
MP = melphalan, prednisone; OS = overall survival; TTP = time to progression. Bortezomib SC not different from IV by
San Miguel et al, 2011; Moreau et al, 2011.

40. 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.

41. 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 protein
IHC = 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

42. 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

43. 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 Detected
NS = normal saline.

44. Case Study: Question 1
You are the nurse caring for this patient. Recall his baseline
laboratory studies. He has anemia, renal insufficiency,
hypercalcemia, and lesions on his bone survey. He will start
Cycle 1 of treatment.
What supportive care therapy would you consider to be
important?
1) Granulocyte stimulating factor (GCSF)
2) Platelet transfusions
3) Bone marrow transplant
4) Bisphosphonates, acyclovir
5) None of the above

45. 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

46. The Evolving Landscape of Myeloma
Treatment: Maintenance Therapy
Beth Faiman, PhD(c), MSN, APRN, BC, AOCN®
Cleveland Clinic Taussig Cancer Institute

47. 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.

48. 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

49. 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.

50. 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 = .0003
Patients (%)
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 advantage
HR = hazard ratio; CI = confidence interval.
Morgan et al, 2010b.

51. 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 induction
CALGB = Cancer and Leukemia Group B; ECOG = Eastern Cooperative Oncology Group; BMT-CTN = Blood and
Marrow Transplant-Clinical Trials Network; CR = complete response; PR = partial response; SD = stable disease;
β2m = beta-2-microglobulin.
McCarthy et al, 2011.

52. 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 arm
TTP = time to progression.
McCarthy et al, 2011.

53. 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 lenalidomide
IFM = Intergroupe Francophone du Myelome; del(13) = deletion 13; VGPR = very good partial response;
Attal et al, 2011.

54. 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
Revlimid
Attal et al, 2011.

55. 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. MP
Palumbo et al, 2011b.

56. 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.

57. 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 years
CAD = coronary artery disease; GCSF = granulocyte colony-stimulating factor; PBSCT = peripheral blood stem cell transplant.
Sonneveld et al, 2010.

58. 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 2010-15:14:34
10 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.

59. 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 analysis
ISS = International Staging System.
Sonneveld et al, 2010.

60. 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 available
FISH = fluorescent in situ hybridization.
Sonneveld et al, 2010.

61. 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

62. 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)

63. The Evolving Landscape of
Myeloma Treatment:
Relapsed/Refractory Disease
Beth Faiman, PhD(c), MSN, APRN, BC, AOCN®
Cleveland Clinic Taussig Cancer Institute

64. 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?

65. 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 intervention
MDE = myeloma-defining event; sFLC = serum free light chain; BJP = Bence Jones protein.
Lonial, 2010; Bird et al, 2011; Anderson et al, 2008.

66. 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, neuropathy
Bird et al, 2011; Anderson et al, 2008.

67. 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 treatment
PD = progressive disease.
Lonial, 2010; Anderson et al, 2008.

68. 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 therapy
CNS = central nervous system.
Mohty et al, 2012; Richardson et al, 2010; Lonial, 2010.

69. 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. combination
NCCN, 2012; Laubach et al, 2009; Blade et al, 2009.

70. 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 Options
Tx = therapy; Bz = bortezomib; PN = peripheral neuropathy; IMiD = immunomodulatory drugs.
Lonial et al, 2011.

71. 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 Options
DCEP vs. DT-PACE = dexamethasone/cyclophosphamide/etoposide/cisplatin vs.
dexamethasone/thalidomide/cisplatin/doxorubicin/cyclophos/phanide/etoposide; Len = lenalidomide.
Lonial et al, 2011.

72. Agents in Phase III Studies
Target Combination Partner(s)
Pomalidomide Dexamethasone
Carfilzomib Lenalidomide, Dexamethsone
Vorinostat Bortezomib
Panobinostat Bortezomib
Elotuzumab Lenalidomide, Dexamethsone
Perifosine Bortezomib
Courtesy of US NIH, 2012.

73. Molecular Structure of Thalidomide,
Lenalidomide, and Pomalidomide
 Structurally similar, but functionally different both qualitatively and quantitatively
DVT = deep vein thrombosis.
Kotla et al, 2009; Thalomid® prescribing information, 2010; Revlimid® prescribing information, 2010.

74. 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 patients
POM = 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.

75. Relapsed and Refractory Myeloma
Single Agent: Pomalidomide (cont.)
100 100
POM + LoDEX POM + LoDEX
80 POM 80 POM
Patients (%)
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 months
PFS = progression-free survival; OS = overall survival.
Richardson et al, 2011.

76. 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 months
CBR = clinical benefit response; ORR = overall response rate.
Siegel, Martin, et al, 2010.

77. 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.

78. 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 reached
IMWG = International Myeloma Working Group.
Lonial et al, 2011.

79. 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 only
MR = minimal response; Bz = bortezomib.
Richardson et al, 2011.

80. 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

81. 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

82. Patient Perspective
Pat Killingsworth
Columnist for the Myeloma Beacon

83. Oncology Nurses Rock!
A Long, 5-Year Rollercoaster Ride
How to Help Newly Diagnosed
Patients Cope: Take a TIME-OUT!

84. Ignore Median Expectancy Numbers
Help Patients Build A Healthcare Team
Don’t Rush to Transplant – Do Your
Homework First

85. Multiple Myeloma Patient Resources
International 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