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SLIDESMultiple Myeloma Highlights From the
2015 ASCO & EHA Annual Meetings
Multiple Myeloma Highlights From the 2015 ASCO Annual Meeting and the 20th Congress of EHA
July 13, 2015
Welcome and Introductions
Anne Quinn Young, MPHMultiple Myeloma Research Foundation
Norwalk, CT
2
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SLIDESMultiple Myeloma Highlights From the
2015 ASCO & EHA Annual Meetings
Multiple Myeloma Highlights From the 2015 ASCO Annual Meeting and the 20th Congress of EHA
Shaji Kumar, MDMayo Clinic
Rochester, MN
Jeffrey Wolf, MDUniversity of California San Francisco
San Francisco, CA
Faculty
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Multiple Myeloma Highlights From the 2015 ASCO Annual Meeting and the 20th Congress of EHA
4
Jeffrey Wolf, MDUniversity of California San Francisco
San Francisco, CA
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SLIDESMultiple Myeloma Highlights From the
2015 ASCO & EHA Annual Meetings
5
Improvement in Overall Survival in the Treatment of Myeloma (By Decade)
1961-701971-801981-901991-20002001-2010
Follow up from Diagnosis (Years)
Pro
po
rtio
n S
urv
ivin
g
0 2 4 6 8 10 12 14 16 18 20
0.0
0.2
0.4
0.6
0.8
1.0
Wolf J Presentation at 2015 ASCO
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Diagnostic Criteria for MGUS, SMM, and MM
< 3 g/dL serum
AND
< 10%
AND
Absent
MGUS
Present(serum/urine)
AND
> 10%b
AND
Present
MM
3 g/dL serum
AND/OR
10-60%
AND
Absent
SMM
Monoclonal Component
Bone MarrowPlasma Cells (%)
End-organ Damage
Mateos M-V. Presentation at ASCO 2015
MGUS, monoclonal gammopathy of undetermined significance; MM, multiple myeloma; SMM, smoldering multiple myeloma.
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SLIDESMultiple Myeloma Highlights From the
2015 ASCO & EHA Annual Meetings
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New Definitions for Smoldering Multiple Myeloma and Symptomatic Multiple Myeloma
Changes to smoldering classification criteria
CRAB criteria
Calcium elevation
Renal insufficiency
Anemia
Bone disease
Plasmacytosis ≥60%
Light chains involved/uninvolved >100
≥1 focal lesion on magnetic resonance imaging (MRI)
Rajkumar et al. Lancet Oncol. 2014;15(12):e538.
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monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM)
Asymptomatic Symptomatic
ACTIVE MYELOMA
M-p
rote
in (
g/L
)
20
50
100
FIRST RELAPSE
SECOND
RELAPSEREFRACTORY RELAPSE
First-line therapy
Plateau remission
Second-line Third-line
Myeloma is always preceded by MGUS or SMM
Mateos M-V. presentation at ASCO 2015
Natural History of Multiple Myeloma
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SLIDESMultiple Myeloma Highlights From the
2015 ASCO & EHA Annual Meetings
9
Smoldering Multiple Myeloma
All patients with smoldering myeloma are not equal
Probability of progression to symptomatic disease increases with increased number of risk factors:
− Evolving M protein pattern
− Immunoparesis
− Bone marrow plasma cell involvement ≥20%
Time to Progression to Symptomatic Myeloma, Years
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30
0.0
0.2
0.4
0.6
0.8
1.0
On
e M
inu
s C
um
ula
tive
Su
rviv
al
No risk factors
1 risk factor
3 risk factors P < 0.001
2 risk factors
Mateos M-V. Presentation at ASCO 2015; de Larrea et al. Blood. 2014;124(21):Abstract 3363
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Transplant Inelegible Patients
Update from the FIRST study
Newly diagnosed
patients
Continuous lenalidomide/dex (N = 535)
18 cycles of lenalidomide/dex (N = 541)
12 cycles of melphalan, prednisone, thalidomide (N = 547)
Median follow-up of 45.5 months
Cont. Len/dex 18 cycles Len/dex MPT
Median OS (months)
58.9 56.7 48.5
Facon T et al J Clin Oncol 33, 2015 (suppl; abs 8524)
MPT, melphalan–prednisone–thalidomide; OS, overall survival
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SLIDESMultiple Myeloma Highlights From the
2015 ASCO & EHA Annual Meetings
11
Transplant Versus No Transplant
Lenalidomide, dexamethasone
6 cycles: cyclophosphamide, lenalidomide, dexamethasone
(CRD)
Mel200/ASCT
N = 389 Mel200/ASCT CRD P value
4-year PFS 87% 71% 0.028
Grade 3 or 4 hematologic AEs 84% 26% 0.001
Grade 3 or 4 non-hematologic AEs 39% 22% 0.008
Gay F et al. EHA 2015 (abs S101)
AE, adverse event; ASCT, autologous stem cell transplant; PFS, progression-free survival.
Maintenance With Lenalidomide(Revlimid)
Holstein SA et al J Clin Oncol 33, 2015 (suppl; abs 8523)
Time to progression and overall survival were significantly improved
− Regardless of response
Lenalidomide may be associated with a risk of secondary primary malignancies
ASCTCRPRSD
Placebo
Lenalidomide
Time to Progression Overall Survival
Time Since ASCT (Months)
Pro
ba
bil
ity
0.0
0.2
0.4
0.6
0.8
1.0
Placebo
Time Since ASCT (Months)
Pro
ba
bil
ity
0.0
0.2
0.4
0.6
0.8
1.0
0 20 40 60 80 1000 20 40 60 80 100
LenalidomidePlaceboLenalidomide
Median: 53 vs 26 mosHazard ratio 0.54(p<0.001)
Median: NR vs 76 mosHazard ratio 0.60(p=0.001)
CR, complete response; NR, not reached; PR, partial response; SD, stable disease.
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SLIDESMultiple Myeloma Highlights From the
2015 ASCO & EHA Annual Meetings
Lenalidomide (Revlimid) Plus Dexamethasone ±ASCT
Lenalidomide, dexamethasone
Collect Collect stem cells
Lenalidomide, dexamethasone
(N = 29)
ASCT(n = 31)
Continue lenalidomide,
dexamethasone
Response rates, progression-free survival, and overall survival were similar in patients with and without ASCT
Lentzsch S et al J Clin Oncol 33, 2015 (suppl; abs 8530)
Overall Survival Progression-free Survival
Time from First Treatment (Months)
Pro
po
rtio
n A
live
0.0
0.2
0.4
0.6
0.8
1.0
0 6 12 24 30 36 42 48 54 66 7860 7218
Arm A (Ld+ASCT) Arm B (Ld alone)
Time to Progression or Death (Months)
Pro
po
rtio
n A
live
or
Pro
gre
ssio
n F
ree
0.0
0.2
0.4
0.6
0.8
1.0
0 6 12 24 30 36 42 48 54 66 7860 7218
HR (Arm B [Ld alone]: Arm A [Ld+ASCT] = 0.73; 95% CI, 0.26–2.01; p=0.54
Arm A (Ld+ASCT) Arm B (Ld alone)
HR (Arm B [Ld alone]: Arm A [Ld+ASCT] = 1.02; 95% CI, 0.51–2.05; p=0.96
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MMRC Phase 2 Trial; Carfilzomib in Newly Diagnosed Patients
Phase 2 trial from the MMRC Open-label, single-arm Primary endpoint: rate of sCR after 8 cycles of carfilzomib
(Kyprolis), lenalidomide (Revlimid), and dexamethasone
ASCTMaintenance
with RdMaintenance
with KRdInduction Consolidation
Cycles 1-4 Cycles 19+Cycles 9-18Cycles 5-8
Zimmerman TM et al J Clin Oncol 33, 2015 (suppl; abs 8510)
CR, complete response; KRd, Kyprolis–Revlimid–dexamethasone; nCR, near complete response; Rd, Revlimid–dexamethasone; sCR, stringent complete response; VGPR; very good partial response.
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SLIDESMultiple Myeloma Highlights From the
2015 ASCO & EHA Annual Meetings
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MMRC Phase 2 Trial (cont.); MinimalResidual Disease
*MRD by 10-color flow cytometry from indicated number of patients available for MRD evaluation
Carfilzomib plus lenalidomide and dexamethasone with ASCT produced higher rates of sCR than was seen previously with this treatment without transplant
Responses improved with duration of treatment
Adverse events were as expected with this treatment
Zimmerman TM et al J Clin Oncol 33, 2015 (suppl; abs 8510)
MRD, minimum residual disease.
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ASPIRE Phase 3 Trial
Relapsed / refractory1-3 prior therapies
Carfizomib, lenalidomide and dexamethasone
Lenalidomide and dexamethasone
Dimopoulos MA et al J Clin Oncol 33, 2015 (suppl; abs 342); Dimopoulos MA et al EHA abs S427
1 prior therapy ≥2 prior therapies
No prior therapies Carf/Len/dex Len/dex Carf/Len/dex Len/dex
PFS (months) 29.6 17.6 25.8 16.7
ORR 87% 70% 87% 64%
Stringent CR 13% 3% 15% 5%
CR 21% 4% 15% 6%
VGPR 42% 36% 34% 28%
PR 11% 27% 23% 26%
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SLIDESMultiple Myeloma Highlights From the
2015 ASCO & EHA Annual Meetings
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ENDEAVOR Phase 3 Trial
Relapsed / refractory
Carfilzomib plus dexamethasone
N = 464
Bortezomib plus dexamethasone
N = 465
Dimopoulos MA et al J Clin Oncol 33, 2015 (suppl;abs 8509); Dimopoulos MA et al EHA LB2071
Carfilzomib/dex Bortezomib/dex
ORR 77% 63%
CR 13% 6%
≥VGPR 54% 29%
Patients had received 1-3 prior treatments Treated until disease progression or unacceptable toxicity Median PFS with carfilzomib was 18.7 months vs 9.4 months with bortezomib
(P< .0001) Rates of grade ≥ 2 peripheral neuropathy were 6.3% vs 32.0% (P< .0001)
ORR, overall response rate.
Summary
Anne Quinn Young, MPHMultiple Myeloma Research Foundation
Norwalk, CT
18
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SLIDESMultiple Myeloma Highlights From the
2015 ASCO & EHA Annual Meetings
Multiple Myeloma Highlights From the 2015 ASCO Annual Meeting and the 20th Congress of EHA
19
Shaji Kumar, MDMayo Clinic
Rochester, MN
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Panobinostat: Update FromPANORAMA 1
Panobinostat (Farydak) combined with bortezomib and dexamethasone was recently approved for patients with relapsed/refractory multiple myeloma
− Treated with ≥2 prior therapies including IMiDs (lenalidomide, thalidomide, or pomalidomide) and bortezomib
Subgroup analysis showed:
− Progression-free survival benefit in patients with prior treatment with:
IMiDs or bortezomib and IMiDs
Bortezomib and IMiDs and ≥ 2 prior therapies
More patients had nCR or VGPR, and these were associated with longer PFS
San-Miguel JF et al J Clin Oncol 33, 2015 (suppl; abs 8526); Hungria VTM et al J Clin Oncol 33, 2015 (suppl; abs 8575)
IMiD, immunomodulatory drug.
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SLIDESMultiple Myeloma Highlights From the
2015 ASCO & EHA Annual Meetings
21
Ongoing Trials With Panobinostat
Chari A et al J Clin Oncol 33, 2015 (suppl; abs 8528)
Panobinostat, lenalidomide, and dexamethasone
Patients had a median of 3 prior therapies
− 15 (74%) were refractory to lenalidomide
− 7 (35%) refractory to pomalidomide− 9 (45%) refractory to bortezomib− 6 (30%) refractory to carfilzomib
ORR was 45%− 1 CR, 3 VGPR, 5 PR
Additionally, there were 8 MR, 2 SD, and 1 PD for a clinical benefit rate of 85%
No grade 3 or 4 gastrointestinal toxicities reported
Panobinostat Plus Carfilzomib All patients had received prior
bortezomib and/or carfilzomib− 81% had received prior IMiDs− 58% previously had ASCT
Responses so far:− 1 (3%) CR, 10 (29%) VGPR, 14
(45%) PR, 4 (13%) MR, 4 (13%) SD− ORR was 77%
Most gastrointestinal toxicities were grade 1 or 2
Grade 3/4 toxicities:− Thrombocytopenia (47%) − Neutropenia (8%)− Anemia (9%)− Diarrhea (6%)
MR, minimum response.
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ELOQUENT Phase 3 trial
Relapsed/Refractory1-3 prior therapiesnot lenalidomide
refractory
Elotuzumab, lenalidomide, and dexamethasone(N = 321)
Lenalidomide and dexamethasone(N = 325)
Lonial S et al J Clin Oncol 33, 2015 (suppl; abs 8508)
Elo/Len/dex Len/dex P value
PFS (months) 19.4 14.9 0.0004
ORR 79% 66% 0.0002
Median number of prior therapies was 2 Elotuzumab added very little toxicity
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SLIDESMultiple Myeloma Highlights From the
2015 ASCO & EHA Annual Meetings
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Phase 2 Trial: Daratumumab
Relapsed/refractory1-3 prior therapies
Daratumumab 16 mg/kg(N = 106)
Lonial S et al J Clin Oncol 33, 2015 (suppl; abs LBA8512)
Median of 5 prior therapies
Median time to progression: 3.7 months
ORR: 29.2%
− 3 sCR, 10 VGPR, and 18 PR
Median duration of response: 7.4 months
Estimated 1-year OS: 65%
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Novel Agents & New CombinationsFor Relapsed, Refractory Patients
Drug Class
CAR-T cells Immunotherapy
CUDC-907 Histone deacetylase inhibitor
Ixazomib Oral proteasome inhibitor
Melflufen Alkylator
MOR202 Monoclonal antibody against CD38
Oprozomib Oral proteasome inhibitor
Ricolinostat Histone deacetylase inhibitor
SAR650984 Monoclonal antibody against CD38
Venetoclax (ABT-199) BCL-2 inhibitor
Raab M EHA 2015, abs S789; Raab M ASCO abs 8574; Raje N et al EHA 2015 P279; Magarotto V et al EHA P285; Moreau P EHA P289; Kumar S EHA P658; Oki Y et al EHA P325; Vij R et al EHA P646
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SLIDESMultiple Myeloma Highlights From the
2015 ASCO & EHA Annual Meetings
Summary
Anne Quinn Young, MPHMultiple Myeloma Research Foundation
Norwalk, CT
25
Shaji Kumar, MDMayo Clinic
Rochester, MN
Jeffrey Wolf, MDUniversity of California San Francisco
San Francisco, CA
Question and Answer
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Multiple Myeloma Highlights From the 2015 ASCO Annual Meeting and the 20th Congress of EHA
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