bristol myerd squibb American Society of Clinical Oncology (ASCO) Highlights
Highlights from ASCO 2010
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Transcript of Highlights from ASCO 2010
HIGHLIGHTS FROM ASCO 2010
Tables and figures from selected presentations
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MPR versus Tandem MEL200 + ASCT as Consolidation Therapy in NDMM
Rd(N = 402)
MPR(n = 202)
MEL200(n = 200)
P value(MPR vs. MEL200)
Efficacy
CR, %VGPR, %PR, %
63149
134236
163738
NSNSNS
PFS at 12 months, % — 91 91 NS
OS at 12 months, % — 97 98 NS
Grade 3/4 AEs
HematologicNeutropenia, %Thrombocytopenia, %
93
458
8687
< 0.001< 0.001
Non-hematologicInfectionsGastrointestinal
——
00
1523
< 0.001< 0.001
Adapted from Palumbo AP, et al. ASCO 2010. Abstract 8015 (oral presentation).
INDUCTION CONSOLIDATION
NS, not significant
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Meta-analysis of MP vs. MPT
GIMEMA IFM I IFM II NMSG HOVON TMSG
Age, years > 65 65-74 > 75 > 65 > 65 > 55
N 331 321 229 354 333 114
Placebo No No Yes Yes No No
Melphalan 4 mg/m2 0.25 mg/kg 0.20 mg/kg 0.25 mg/kg 0.25 mg/kg 9 mg/m2
Prednisone 40 mg/m2
days 1-72 mg/kgdays 1-4
2 mg/kgdays 1-4
100 mgdays 1-4
1 mg/kgdays 1-5
60 mg/m2
days 1-4
No. of cycles 6 12 12 Until plateau ≥ 8 8
No. of weeks per cycle 4 6 6 6 4 6
Thalidomide 100 mg 200-400 100 200-400 200 100
Duration of thalidomide Until relapse 12 cycles 12 cycles Until relapse 4 weeks after
last cycle 8 cycles
Adapted from Waage A, et al. ASCO 2010. Abstract 8130 (poster presentation).
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Carfilzomib in R/R MM
BTZ-treatedCohort 1 (n = 36)
BTZ-naïveCohort 1 (n = 59)
BTZ-naïveCohort 2 (n = 60)
Carfilzomib dose 20 mg/m2 20 mg/m2 20 mg/m2 cycle 127 mg/m2 cycle 2+
Evaluable for response 34 53 53
Overall response rate (≥PR) 21% 45% 55%
Median duration of response (≥MR) 8.5 months 8.3 months 11.5 months
Median time to progression 8.1 months 8.3 months 11.5 months
Adapted from Vij R, et al. ASCO 2010. Abstract 8000 (oral presentation).
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New Combinations with Lenalidomide/dex in R/R MM Presented at ASCO 2010
CARFILZOMIB PANOBINOSTAT VORINOSTAT EVEROLIMUS ELOTUZUMAB
Author/Abstract No. Bensinger/8029 Mateos/8030 Richardson/8031 Mahindra/8032 Lonial/8020
Study phase 1b 1b 1 1 1/2
N 84 46 31 26 29
Dose-limiting toxicities
None observed (MTD not reached)
Neutropenia, febrile neutropenia,
thrombocytopenia, cardiac issues,
metabolic issues
Diarrhea Neutropenia, thrombocytopenia None observed
Selected ≥Grade 3 AEs
Neutropenia, thrombocytopenia,
anemia
Neutropenia, thrombocytopenia,
anemia
Neutropenia, thrombocytopenia, diarrhea, anemia,
fatigue
Neutropenia, thrombocytopenia
Febrile neutropenia, sepsis, enteritis,
diarrhea
ORR (≥PR)Prior lenalidomidePrior thalidomidePrior bortezomib
67%32/54 (59%)27/34 (79%)34/59 (58%)
41%0/4——
52%5/13 (38%)
——
11%———
82%
Adapted from Bensinger (abs 8029), Mateos (abs 8030), Richardson (abs 8031), Mahindra (abs 8032), Lonial (abs 8020).
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New Combinations with Bortezomib in R/R MM Presented at ASCO 2010
PANOBINOSTAT ELOTUZUMAB VORINOSTAT
Author/Abstract No. San-Miguel/8001 Jakubowiak/8003 Jagannath/8133
Study phase(s) 1b 1 2b/3
N 47 28 83/172
Dose-limiting toxicities
Neutropenia, thrombocytopenia, pneumonia, fatigue, asthenia, dizziness, gastric hemorrhage
None observed Not reported
Selected ≥Grade 3 AEs
Thrombocytopenia, neutropenia, anemia, leukopenia, asthenia,
respiratory tract infection
Lymphopenia, fatigue, chest pain,
gastroenteritis
Thrombocytopenia, nausea, diarrhea
ORR (≥PR)
55%(all patients)
9/15 (60%)(bortezomib-refractory)
48%(all patients)
6/11 (55%)(prior bortezomib)
7/43 (16%)(bortezomib-refractory;
median 4.5 prior regimens)
Adapted from San-Miguel (abs 8001), Jakubowiak (abs 8003), Jagannath (abs 8133).
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Romidepsin Shown to be Active in All 3 Disease Compartments in CTCL
ORR (PR + CR)n/N
CRn/N
Skin≥50% reduction in SWAT or erythroderma
40%(38/96)
8%(8/96)
Lymph node≥30% reduction in SLD
35%(13/37)
14%(5/37)
Blood≥50% reduction in Sézary cells
77%(10/13)
0
Skin + lymph node + bloodComposite endpoint
34%(33/96)
6%(6/96)
Adapted from Kim E, et al. ASCO 2010. Abstract 8047 (poster presentation).
SLD = sum of longest diameterSWAT = severity-weighted assessment tool
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Denileukin Diftitox in CTCL
Placebo(n = 44)
Total DD(n = 263)
DD-naïve9 μg/kg(n = 80)
DD-naïve18 μg/kg(n = 118)
DD-treated18 μg/kg(n = 29)
DD-naïve18 μg/kg(n = 36)
Baseline stage ≤IIa 30 154 43 69 21 21
Baseline stage ≥IIb 14 109 37 49 8 15
ORR, % 16 38 31 47 28 31
Median duration of response, days 81 277 277 267 274 340
P value duration of response vs. placebo
— < 0.0001 0.0297 < 0.0001 0.0082 0.0036
CD25+ CD25–
Adapted from Duvic M, et al. ASCO 2010. Abstract 8055 (poster presentation).
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CALGB 100104: TTP and OS
TIME TO PROGRESSION OVERALL SURVIVAL
Median Follow-up from randomization is 12 months
LenalidomideMedian TTP not reached
PlaceboMedian TTP 25.5 months
1.0
0.8
0.6
0.4
0.2
0.0
1.0
0.8
0.6
0.4
0.2
0.0
Prob
abili
ty
0 200 400 600 800 1000 1200 1400
Time since ASCT (days)0 200 400 600 800 1000 1200 1400
Time since ASCT (days)
Not long enough follow-up to determine difference in OS
Lenalidomide
Placebo
Lenalidomide arm: 11 deaths Placebo arm: 17 deaths
(P < 0.2)
Adapted from McCarthy PL, et al. ASCO 2010. Abstract 8017 (oral presentation).
10Lenalidomide Consolidation and Maintenance following First-line ASCT (3-year PFS)
0.00
0.25
0.50
0.75
1.00
0 6 12 18 24 30 36
HR 0.46P < 10–7
Lenalidomide3-year PFS: 68%
Placebo3-year PFS: 34%
Months
Prob
abili
ty
Adapted from Attal M, et al. ASCO 2010. Abstract 8018 (oral presentation).