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Multiple Myeloma in 2014:
What Advanced Practice Providers Should Know
November 2014
Scottsdale, ArizonaScottsdale, Arizona Rochester, MinnesotaRochester, Minnesota Jacksonville, FloridaJacksonville, Florida
Joseph Mikhael, MD, MEd, FRCPCStaff Hematologist, Mayo Clinic Arizona
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Objectives
1. Provide an overview of the types and spectrum of multiple myeloma
2. Discuss the “significance” of MGUS and its practical management
3. Review the diagnosis and staging of myeloma
4. Discuss the approach to therapy, including stem cell transplantation
5. Highlight the improvement in prognosis for patients with myeloma
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Myeloma case
68 yo male
• 9 month history of low back pain
• Treated by FP, PT, Chiropractor – no improvement
• FP did plain x-rays, revealed multiple lytic lesions
• Gradual increasing fatigue, SOBOE
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Case cont.
• Hb 7.8, WBC 5.6, Plts 132
• Ca 10.8, Creat 1.6
• IgG Level 5800 (A and M depressed)
• No Bence Jones proteinuria
• Bone Marrow: 60% plasmacytosis
• CRP normal, Albumin 3.4
• B2M elevated
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Case contd.
• Does he have Myeloma?
• What is your first step?
• What to do about his hypercalcemia?
• What to do about his anemia?
• What to do about his bony disease?
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Epidemiology
• 1% of malignancies
• 10% of Heme cancers
• 21000 Americans annually
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Epidemiology
• Men > Women
• Blacks > Whites
• Median age of diagnosis is 66• 10% < 50, 2% <40
M-proteinNormal
+ - + -
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Pathophysiology
• Malignant plasma cell dyscrasia
• Accumulation of plasma cells in the bone marrow
• These produce a single immunoglobulin (Ig) – monoclonal protein
• Sequelae relate to presence of plasma cells or interactions they induce via cytokines in microenvironment
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The Plasma Cell
Carr and Rodak: Clin Hematol Atlas
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The malignant clone
Bone Marrow
Lymph node
IgG,A,D,E plasma cell
IgM
hypermutationlymphoblastplasmablast
pre-B cell
somatic
Plasma cell
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How do plasma cells become “evil”?
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Immunoglobulins
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Kyle, R. A. et al. N Engl J Med 2004;351:1860-1873
Mechanisms of Disease Progression in the Monoclonal Gammopathies
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Molecular progression
Normal plasma
cell
Asymp-tomatic
Myeloma
Aggressive Myeloma
Active Myeloma
Del 13Secondary translocations
TranslocationsInfection
Inflammation
ras & p53 mutationc-myc dysregulation
Bone resorptionAngiogenesis
MGUS
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The Spectrum of Myeloma
MGUS Asymptomatic MM (smouldering)
“True” MM PC Leukemia
Organ damage
none none yes yes
Marrow Disease
<10% plasma cells
≥ 10% plasma cells
≥ 10% plasma cells
Plasma cells in blood
Management Monitor 1-2 times/yr
Close follow up (q 3 mts)
therapy Highdose combo chemo
Transforma-tion rate
1% /yr 10-20%/yr n/a n/a
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MGUS
Monoclonal Gammopathy of Unknown Significance
• Presence of a serum monoclonal protein (concentration ≤ 3g/dL)
• Less than 10% plasmacytosis in marrow
• No evidence of End-Organ damage (CRAB)• Calcium elevation, Renal Insufficiency,
Anemia, Bony disease
• Asymptomatic
• No co-existing plasma cell dyscrasia or lymphoproliferative disease (table)
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Diseases associated with a monoclonal gammopathy
• Plasma cell disorders• Monoclonal gammopathy of undetermined significance
(MGUS)• Biclonal gammopathy of undetermined significance• Idiopathic Bence Jones proteinuria• POEMS syndrome, Osteosclerotic myeloma• Castleman's disease• AL (light chain) amyloidosis• Solitary plasmacytoma• Multiple myeloma, Smoldering multiple myeloma
• B-cell lymphoproliferative disorders• Non-Hodgkin's lymphoma• Chronic lymphocytic leukemia• Lymphoplasmacytic lymphoma (Waldenstrom
macroglobulinemia)• Post-transplant monoclonal gammopathies
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Epidemiology
• Prevalence is approximately 1-3% in adults in the USA, Sweden, France and Japan1
• Higher as we age:• ≥ 50: 3.2%• ≥ 70: 5.3%• ≥ 85: 7.5%2
• 2-3 fold higher incidence in Africans and African American population3
• Annual risk of transformation to MM or related diseases of 1%4
1 Kyle Blood 1972, Axelsson Acta Med Scan 1986, Saleun J Clin Path 1982, Iwanaga Mayo Clin Proc 2007; 2 Kyle NEJM 2006; 3 Singh J Lab Clin Med 1990, Cohen AM J Med 1998, Landgren Blood 2006; 4 Kyle et al NEJM 2002
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Kyle R et al. N Engl J Med 2002;346:564-569
Risk of Progression among 1384 Residents of Southeastern Minnesota in Whom Monoclonal Gammopathy of Undetermined Significance was Diagnosed in 1960 through 1994
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MGUS Progression
• Potential Predictive Factors of Progression
• M protein size1
• IG class: IgA>IgM>IgG2
• Bone marrow plasmacytosis3,4
• Presence of urinary Bence Jones proteinuria3
• Free Light Chain Assay5
1 Kyle NEJM 2002, 2 Kyle Blood 2003, 3 Cesana JCO 2002, 4 Perez-Persona Blood 2007 5 Rajkumar BJH 2004
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Copyright ©2005 American Society of Hematology. Copyright restrictions may apply.
Rajkumar, S. V. et al. Blood 2005;106:812-817
Figure 3. Risk of progression of MGUS to myeloma or related disorder using a risk-stratification model that incorporates the FLC ratio and the size and type of the serum
monoclonal protein
20 year
58%
37%
21%
5%
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Monitoring
• No absolute consensus
• Algorithm:• Make accurate diagnosis• Obtain baseline bloodwork (incl total Igs and
FLC), 24 hr urine and skeletal survey• Repeat testing (history, physical, blood work
only) at 6 months• If lower risk, can be seen annually (assuming
asymptomatic)• If higher risk, I prefer every 6 months
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Bone Marrow
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Diagnosis of Myeloma
The diagnosis of Myeloma is made as a result of several tests:1. Blood Counts (CBC – white, red, platelets)2. Blood and urine tests for immune proteins
– IgG, IgA, IgM – total number (combination of normal protein and abnormal or “M” protein)
– May also be “light chains” which are component of abnormal protein
– May require 24 hour urine collections
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Diagnosis of Myeloma contd.3. Bone Marrow tests (aspirate and biopsy)
– This looks for the % of plasma cells in the marrow
– Also looks for abnormal cytogenetics of the plasma cells and FISH analysis
4. X-rays
looking for osteopenia, lytic lesions and fractures (NOT a bone scan)
possibly MRI of the spine
5. Other blood tests
creatinine, calcium, albumin beta-2-microglobulin
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Multiple Myeloma - Types
• Subtypes of MM are determined based on the kind of abnormal protein
IgG – 55%IgA – 25%IgD – 1-2%IgM – 1%Light Chain Disease only – 20%Non Secretors 1-2 %
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M spike in gamma region
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Multiple Myeloma
• Unfortunately, MM is not a curable disease (yet!!)
• Historically most people did not live for much more than 2 years…
• However, the average survival is now at least 8 years
• This has been a result of two key developments:1. Autologous Stem Cell Transplant2. Novel Drugs (thalidomide, bortezomib,
lenalidomide, carfilzomib, pomalidomide)
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Myeloma Staging
• Older system of Salmon-Durie staging• Not as useful anymore
• Newer system of using 2 factors:• Albumin and Beta-2-microglobulin• It is “prognostic” for survival
• Practically, there are 2 stages1. Can wait and watch2. Requires treatment
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Cytogenetics
• These are the genes of the plasma cells (not the patient)
• May indicate more about the biology of the disease
• Most can be found at diagnosis, but others may be “acquired” later
• Could well be the most “prognostic” tool in myeloma as it may separate “high risk” myeloma from standard risk
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0.0
0.2
0.4
0.6
0.8
1.0
0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150
Su
rviv
al p
rob
abil
ity
Su
rviv
al p
rob
abil
ity
MonthsMonths
P<0.001P<0.001
t(4;14)t(14;16)-17p13
t(4;14)t(14;16)-17p13
1313
All others includingt(11;14)All others includingt(11;14)
Poor 24.7 mosIntermediate 42.3 mosGood 51.0 mos
Poor 24.7 mosIntermediate 42.3 mosGood 51.0 mos
Fonseca et al Blood 101:4569, 2003
Molecular Prognostic ModelMolecular Prognostic Model
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Myeloma Treatment
Principles of therapy
1. Stop the production of the abnormal plasma cells (chemo)
2. Strengthen the bone and prevent fractures
3. Increase the hemoglobin count and reduce fatigue
4. Reduce risk of infections
5. Promote well being and quality of life
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Treatment with Chemotherapy
• Goal is to reduce the number of plasma cells and the proteins they produce
• Timing is important as it may be possible to wait & watch
• It is not “curative” but may put the disease into remission
• Must be tailored to individual based on disease factors (type, severity, organs involved) and patient factors (age, general health…)
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Managing myeloma: the components
Supportive Care
Initial Therapy
Consolidation Maintenance
Treatment of Relapsed
disease
Transplant EligiblePatients
Transplant Ineligiblepatients
Consolidation/ Maintenance/ Continued therapy
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Mayo Stratification for Myeloma And Risk-adapted Therapy
Newly Diagnosed Myeloma
Website: www.msmart.org
mSMART
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mSMART 2.0: Classification of Active MM
FISH Del 17p t(14;16) t(14;20)
GEP High risk
signature
All others including: Hyperdiploid t(11;14)** t(6;14)
FISH t(4;14)‡
Cytogenetic Deletion 13 or hypodiploidy
PCLI >3%
High-Risk Intermediate-Risk* Standard-Risk*†
Mikhael et al Mayo Clinic Proceedings April 2013
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mSMART 2.0: Classification of Active MM
FISH Del 17p t(14;16) t(14;20)
GEP High risk
signature
All others including: Hyperdiploid t(11;14) t(6;14)
FISH t(4;14)*
Cytogenetic Deletion 13 or hypodiploidy
PCLI >3%
High-Risk 20% Intermediate-Risk 20% Standard-Risk 60%
3 years 4-5 years 8-10 years
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mSMART – Off-StudyTransplant Eligible
a Bortezomib containing regimens preferred in renal failure or if rapid response neededb If age >65 or > 4 cycles of Rd Consider G-CSF plus cytoxan or plerixaforc Continue Rd for patients responding to Rd and with low toxicities; Dex is usually discontinued after first year* Consider risks and benefits; consider limited duration 12-24 months
Standard Risk
Autologous stem cell transplant
4 cycles of Rda or CyBorD
Collect Stem Cellsb
Continue Rd;
c or
CyBorD for ~12 months
High Risk
4 cycles of VRd
Intermediate Risk
Autologous stem cell transplant
Bortezomib based therapy for minimum of 1 year
4 cycles of CyBorD
Autologous stem cell transplant, especially if
not in CR
V or VCd for minimum of 1 year
2 cycles of Rd consolidation; Then Len maintenance if not in VGPR and Len responsive*
Dispenzieri et al. Mayo Clin Proc 2007;82:323-341; Kumar et al. Mayo Clin Proc 2009 84:1095-1110; Mikhael et al. Mayo Clin Proc 2013;88:360-376. v11 //last reviewed Dec 2013
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mSMART – Off-StudyTransplant Ineligible
a Dex is usually discontinued after first yearb Bortezomib containing regimens preferred in renal failure or if rapid response needed*Clinical trials strongly recommended as the first option
Intermediate Risk Standard Risk*
MP + weekly Bortezomib or weekly CyBorD for
~12 months
Bortezomib based therapy for minimum of 1 year
High Risk
VRd* for ~12 months, Rda, b
Dispenzieri et al. Mayo Clin Proc 2007;82:323-341; Kumar et al. Mayo Clin Proc 2009 84:1095-1110; Mikhael et al. Mayo Clin Proc 2013;88:360-376. v11 //last reviewed Dec 2013
Continue VRd as maintenance for minimum
of 1 year
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Initial Response
• Please note that the ultimate goal is both DEPTH and LENGTH of response
• Deepest response is “Complete” Remission (=CR) vs partial remission or minimal remission
• It appears that a deeper response (esp CR) may predict a longer remission and even survival
• HOWEVER, trends do not predict any individual patient
• We treat the patient not the disease
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Treatment sequence
Induction Consolidation
Front line treatment
Maintenance
Maintenance
Rescue
Relapsed
VADDEX
SCTNothing
PrednisoneThalidomide
Few options
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Treatment sequence
Induction Consolidation
Front line treatment
Post consolidation
Maintenance
Rescue
Relapsed
OLD VADDEX
SCTNothing
PrednisoneThalidomide
Few options
NEW
Thal/Dex VD
Rev/DexCyBorD
VTDVRD
SCTVD/VRD
NothingThalidomide?Bortezomib?
Lenalidomide?
BortezomibLenalidomideThalidomideCarfilzomib
PomalidomideElotuzumab
HDACBendamustine
Monoclonal Antibodies
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2006-2010 73% 56%
2001-2005 63% 31%
IMPACT OF NOVEL THERAPY 2012/2013
Median 7.3 years
5 YEAR SURVIVAL BY AGE
AGE≤ 65 YRS
AGE> 65 YRS
2012 ASH Abstract #3972 Kumar et al
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Long-Term Survival With CyBorD Induction Therapy In Newly Diagnosed
Multiple Myeloma
Craig B. Reeder, MD, Donna E. Reece, MD, Vishal Kukreti, MD, FRCPC, Joseph Mikhael, MD, Christine I. Chen, MD, Suzanne Trudel, MD, Kristina Laumann, Joseph Hentz, Giovani Piza, Rafael Fonseca, MD, P. Leif Bergsagel, MD, Jose F Leis, MD, PhD, Rodger E. Tiedemann, MBChB, PhD, FRACP, FRCPA, Jacy
Spong, BS, RN, BSN, Angela Mayo, PA/NP and Keith Stewart, MD
Reeder C. et al.; ASH 2013: abstract 3192
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Results - Response
ITT Cohort 1 Cohort 2 All (n=63)
ORR 88% (29/33) 90% (27/30) 89% (56/63)
CR / nCR 36% (12/33) 47% (14/30) 41% (26/63)
>VGPR 61% (20/33) 63% (19/33) 62% (39/63)
After 4 cycles
Cohort 1 Cohort 2 All (n=55)
ORR 96% (27/28) 93% (24/27) 93% (51/55)
CR / nCR 46% (13/28) 48% (13/27) 47% (26/55)
>VGPR 71% (20/28) 63% (17/27) 67% (37/55)Reeder C. et al.; ASH 2013: abstract 3192
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Results - Survival
Progression Free Survival (5 yr)
Overall Survival (5 yr)
ALL(n=63)
42%(95% CI:31-57)
70%(95% CI: 59-82)
Standard Risk (n=39)
48%(95% CI: 33-69)
81%(95% CI: 69-95)
High Risk(n=24)
33%(95% CI: 19-59)
54% (95% CI: 37-78)
Most patients underwent auto stem cell transplant after completing the induction trial and most did not utilize maintenance therapy post SCT.
Reeder C. et al.; ASH 2013: abstract 3192
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LONG-TERM SURVIVAL WITH CYBORD: ASH 20131
1 ASH Abstract #3192 Reeder et al
OS: All PatientsOS 81% at 5 years for
standard risk
OS by Risk Status
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The “NEW” CyBorD
• All three drugs given weekly• Cyclophosphamide 300mg/m2 PO• Bortezomib 1.5 mg/m2 IV or SQ• Dexamethasone 40mg PO
• We consider one cycle a 4 week course
• No “week off”
• Less neuropathy, more convenience, equal efficacy
• Always give viral prophylaxis
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Retrospective, observational study: VCD and VRD as initial treatment for MM
VCD(n= 101)
VRD(n= 75)
Median ageMean treatment durationPts undergoing ASCT
62.7 years5.1
months50%
60.9 years5.4 months
59%
Best response after 4 cycles2-year PFS2-year OS
89%66.6%90.8%
81%63.2%87.4%
Common AEs reported in at least 3 treatment cycles
FatiguePeripheral NeuropathyAnemiaGI
18%11%11%9%
9%16%16%8%
Conclusion: Comparable outcomes with VCD and VRD in terms of response, PFS, OS and similar safety profiles
Kumar et al. ASH 2013: Abstract 3178, poster presentation
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ASH 2012-3: Induction RegimensResponse Rates (%) & Survival
Trial N nCR/sCR >=VGPR >=PR PFS OS
CarCyDex 58 68 76 95 1-yr 86% 1 yr 85%
CarLenDex 41 68 88 96 1 yr ≤ 83 NA
CarThalDex1 50 18 60 92 1 yr 88% NA
MLN9708-Len-Dex
65 23 58 90 1 yr 93% NA
MLN9708-Len-Dex
64 24 67 96 NA NA
CyCarThalDex 54 18 76 91 1 yr 90% 1 yr 98%
R2V2 30 40 73 97 1 yr 97% 1 yr 100%
Blood 120(21) 2012: Sonneveld Abs 333 Kumar Abs 332 Kaufman Abs 336: Len, Bortezomib, Dex, and Vorinostat
Blood 122(21) 2013:Bringhen, Abs 685 Korde, Abs 538 Mikhael, Abs 3179 Richardson Abs 535
1 Induction portion of CTD x 4 followed by HDM and consolidation with CTD x 4
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How Deep a Response Required before ASCT?
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MM06-04-12_6.ppt
Autologous Autologous TransplantTransplant
Diagnosis and Initial Diagnosis and Initial InductionInduction
Autologous Autologous TransplantTransplant
12 months from diagnosis to ASCT12 months from diagnosis to ASCT
Salvage CohortSalvage Cohort
No Salvage CohortNo Salvage Cohort
ASCTDiagnosis
Effect of Pre-transplant Salvage Therapy Prior to Autologous Transplant (ASCT) in Patients Not
Responding to Initial Induction for MM
Salvage Salvage ChemotherapyChemotherapy
< PR to induction< PR to induction
Vij Blood 120(21) 2012, abstract 597
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Outcomes with/without Pre-ASCT Salvage
(Source: Txz12_23 & _24) MM06-04-12_15.ppt
P = NS P = NS
Vij Blood 120(21) 2012, abstract 597
Median follow-up Salvage No Salvage Months 68 (110-180) 61 (9-181)
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Stem Cell Transplant
• Concept: eliminate any remaining abnormal plasma cells in the bone marrow with HIGH dose chemotherapy (ie what may be left after initial chemotherapy)
• Process1. Use initial chemotherapy to reduce plasma cells2. Collect stem cells from bone marrow
a. Mobilization with neupogen (G-CSF) +/- chemob. Collection by pheresis in stem cell unitc. Storage of stem cells (frozen)
3. Admit and give high dose treatment (wipe out current marrow)4. Re-Infuse stem cells previously collected and wait for them to
“grow”
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Patient
Priming Therapy
FreezeCollect PBSCs
High-dose Chemotherapy
Reinfuse PBSCs
+/- Post-ASCT therapy
ASCT
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Autologous Stem Cell Transplantation: Timing
• Most trials incorporate SCT as consolidation therapy after initial treatment
• Trials comparing timing of transplant, as part of initial treatment or after relapse, show better disease free survival with initial SCT but equivalent overall survival
• Currently there is some debate about the role of SCT when novel drugs are used for initial treatment
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Autologous Transplant Improves Responsesafter Traditional or Novel Induction
Sonneveld
JCO 12
Harrouseau
JCO 10
Cavo
Lancet 10
VAD BtzAD VAD BtzD ThalD BtzThalD
Induction
≥nCR
5% 11% 7% 15% 11% 31%
Transplant
≥nCR
15% 31% 18% 35% 31% 52%
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Transplant Ineligible
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FIRST Design: Lenalidomide and Low-dose Dexamethasone (Rd/Rd18) vs. MPT
ARM A
Arm BRd18
Arm CMPT
N = 535
Arm ARd
LEN + Lo-DEX until Progressive DiseaseLENALIDOMIDE 25mg D1-21/28Lo-DEX 40mg D1,8,15 & 22/28
LEN + Lo-DEX: 18 Cycles (72 wks) LENALIDOMIDE 25mg D1-21/28Lo-DEX 40mg D1,8,15 & 22/28
MEL + PRED + THAL 12 Cycles1 (72 wks)MELPHALAN 0.25mg/kg D1-4/42PREDNISONE 2mg/kg D1-4/42THALIDOMIDE 200mg D1-42/42
Active Treatment + PFS Follow-up PhaseScreening LT Follow-Up
Pts > 75 yrs: Lo-DEX 20 mg D1, 8, 15 & 22/28; THAL2 100 mg D1-42/42, Melphalan2 0.2 mg/kg D1–4
• Stratification: age, country and ISS stage
1Facon T, et al. Lancet 2007;370:1209-18; 2Hulin C, et al. JCO. 2009;27:3664-70.
International Staging System; LT, long-term; PD, progressive disease; OS, overall survival
n= 1,623 - 18 countries from North America, Asia-Pacific, and Europe represented from 246 Centers
n=535
n=541
n=547
Facon T. et._ASH 2013: Abstract 2
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FIRST Trial: Final PFSContinuous Rd the risk of PFS events (PD or death) by 28% vs. MPT
mos, months; MPT, melphalan, prednisolone, thalidomide; PFS, progression-free survival; Rd, Lenalidomide plus low-dose dexamethasone.
Median PFS
Rd (n= 535) 25.5 mos
Rd18 (n= 541) 20.7 mos
MPT (n= 547) 21.2 mos
Rd 535 400 319 265 218 168 105 55 19 2 0
Rd18 541 391 319 265 167 108 56 30 7 2 0
MPT 547 380 304 244 170 116 58 28 6 1 0
Hazard ratio
Rd vs. MPT: 0.72; P = 0.00006
Rd vs. Rd18: 0.70; P = 0.00001 Rd18 vs. MPT: 1.03; P = 0.70349
Time (months)
Pat
ien
ts (
%)
100
80
60
40
20
00 6 12 18 24 30 36 42 48 54 60
72 w
ks
Facon T. et._ASH 2013: Abstract 2
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FIRST Trial: Overall Survival Interim Analysis574 deaths (35% of ITT)
Pat
ien
ts (
%)
RdRd18MPT
535541547
488505484
457465448
433425418
403393375
338324312
224209205
121124106
434430
563
000
4-year OS
Rd (n= 535) 59.4%
Rd18 (n= 541) 55.7%
MPT (n= 547) 51.4%
Overall survival (months)
100
80
60
40
20
00 6 12 18 24 30 36 42 48 54 60
Hazard ratio Rd vs. MPT: 0.78; P = 0.0168 ( 22% risk of death with Rd)
Rd vs. Rd18: 0.90; P = 0.307 Rd18 vs. MPT: 0.88; P = 0.184
The pre-specified boundary (p<0.0096) was not crossed for Rd_continuous vs MPT_18 months
Facon T. et._ASH 2013: Abstract 2
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Relapsed Disease
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Treatment sequence
Induction Consolidation
Front line treatment
Post consolidation
Maintenance
Rescue
Relapsed
OLD VADDEX
SCTNothing
PrednisoneThalidomide
Few options
NEW
Thal/Dex VD
Rev/DexCyBorD
VTDVRD
SCTVD/VRD
NothingThalidomide?Bortezomib?
Lenalidomide?
BortezomibLenalidomideThalidomideCarfilzomib
PomalidomideElotuzumab
HDACBendamustine
Monoclonal Antibodies
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Carfilzomib: A Novel Agent Designed to Promote Selective and Sustained Proteasome Inhibition
• Carfilzomib is a next-generation, selective proteasome inhibitor• Potent and sustained target suppression• Improved antitumor activity• Minimal off-target activity with low neurotoxicity
69
HN
NH
O HN
O
O
NHO
NO O
O
EpoxyketoneTetrapeptide
Adapted from: Kuhn DJ, et al. Blood. 2007;110:3281-3290.
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Neuropathy Was Infrequent and Not Dose LimitingPooled data from single-agent studies (003 / 004 / 005)
• Peripheral neuropathy occurred infrequently across all single-agent studies*
• Only 6 patients (1.2%) experienced a Grade 3 PN event
• No Grade 4 PN events
• Only 1 patient had drug discontinued for PN (study 004; BTZ-treated arm)
70Adapted from: Singhal S, et al. ASH 2010. Abstract 1954 (poster presentation).*Includes the terms peripheral neuropathy, neuropathy, peripheral sensory neuropathy, peripheral motor neuropathy
N=505
Did not experience peripheral neuropathy
Grade 3 PN (1.2%)
Grade 1/2 PN (13.4%)
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Carfilzomib - Practical
• Highly effective and very well tolerated
• Beware of tumor lysis hence dosing schedule
• Cardiac issue present but mostly mitigated by fluid management
• Issues of weekly dosing being explored
• Lack of neuropathy very attractive
• Upfront uses increasing
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Molecular Structure of Thalidomide, Lenalidomide and Pomalidomide
Molecular Structure of Thalidomide, Lenalidomide and Pomalidomide
Structurally similar, but functionally different both qualitatively and
quantitatively
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Myeloma Pomalidomide Summary
73
Lacy Pom/Dex1-3 reg
Lacy Pom/DexLen ref
RichardsonPom+/- dex
MM-002
PR 63% 32% 28%
MR 82%* 47% 52%
Median 3 prior regimens
Median 4-6 prior regimens
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Pomalidomide - Practical
• Similar to lenalidomide with slightly less myelotoxicity and fatigue
• Dosing range 2-4mg
• Thromboprophylaxis necessary
• Feasible in combination
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NEWER THERAPIES: ASH 2013
TOP 8
Anti-CD 38 monoclonal antibodies (MAb) daratumumab (abstracts #227 and #1986) and SAR 650984 (#284)
MLN 9708 (ixazomib citrate: abstracts #535, 1944, and 1983) ARRY 520 (abstracts #285 and #1982) ACY-1215 (abstracts #759 and #3190) Selinexor (also known as KPT-330, abstract #279) Anti-CD 138 monoclonal antibody (BT062, indatuximab
ravatansine, abstract #758) Panabinostat (abstract #1970) Bendamustine (abstract #1971)
Anti-CD 38 monoclonal antibodies (MAb) daratumumab (abstracts #227 and #1986) and SAR 650984 (#284)
MLN 9708 (ixazomib citrate: abstracts #535, 1944, and 1983) ARRY 520 (abstracts #285 and #1982) ACY-1215 (abstracts #759 and #3190) Selinexor (also known as KPT-330, abstract #279) Anti-CD 138 monoclonal antibody (BT062, indatuximab
ravatansine, abstract #758) Panabinostat (abstract #1970) Bendamustine (abstract #1971)
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Conclusions
• MGUS is a common condition that must be appropriately managed, including risk stratifying patients
• Multiple Myeloma is an uncommon condition but has improved survival with use of novel agents and stem cell transplant
• Newer agents are showing outstanding results with the recent additions of carfilzomib and pomalidomide
• Although the mainstay of treatment is directed at the cancer itself, considerations must be given to supportive care and quality of life