Multiple Myeloma Update from the American Society of Clinical Oncology ASCO 43rd Annual Meeting

1
Multiple Myeloma Update from the American Society
of Clinical Oncology (ASCO) 43rd Annual Meeting

• Welcome and Introduction

Featuring
Nikhil Munshi, MD Dana-Farber Cancer
Institute Boston, MA
S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN
Moderator
Richard Lutes, MD
2
Multiple Myeloma Update from the American Society
of Clinical Oncology (ASCO) 43rd Annual Meeting

• Upfront Therapy

Featuring
Nikhil Munshi, MD Dana-Farber Cancer
Institute Boston, MA
S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN
3
Lenalidomide/high-dose dexamethasone vs
lenalidomide/low-dose dexamethasone (ECOG trial
E4A03)
Rd
1
0.8
RD
0.6
Probability
0.4
A B
0.2
Log-rank P0.0001
0
25
20
15
10
5
0
Overall survival (mo)
Rajkumar SV, et al, ASCO 2007, Abstract LBA8025.
4
Lenalidomide/high-dose dexamethasone vs
lenalidomide/low-dose dexamethasone (ECOG trial
E4A03)
Rajkumar SV, et al, ASCO 2007, Abstract LBA8025.
5
Lenalidomide/high-dose dexamethasone vs
lenalidomide/low-dose dexamethasone (ECOG trial
E4A03)
Rajkumar SV, et al, ASCO 2007, Abstract LBA8025.
6
Melphalan-prednisone-thalidomide (MPT) vs
melphalan-prednisone (MP) in patients aged 75
years (IFM 01-01 trial)
hulin c, et al, ASCO 2007, Abstract 8001.
7
Melphalan-prednisone-thalidomide (MPT) vs
melphalan-prednisone (MP) in patients aged 75
years (IFM 01-01 trial)
Overall survival by treatment (n200)
MPT Median OS 45.3 mo 33.3 Unreached
Y/N39/100
Proportion
Time from randomization (mo)
Log-rank P0.05 Median follow-up time 24 months
hulin c, et al, ASCO 2007, Abstract 8001.
8
Multiple Myeloma Update from the American Society
of Clinical Oncology (ASCO) 43rd Annual Meeting

• Upfront Therapy
• Discussion

Featuring
Nikhil Munshi, MD Dana-Farber Cancer
Institute Boston, MA
S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN
Moderator
Richard Lutes, MD
9
Multiple Myeloma Update from the American Society
of Clinical Oncology (ASCO) 43rd Annual Meeting

• Transplantation

Featuring
Nikhil Munshi, MD Dana-Farber Cancer
Institute Boston, MA
S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN
10
TTIII plus bortezomib
100
PR
nCR
80
CR
60
Percent of patients ()
40
20
0
Months from Start of Induction
Barlogie B, et al, ASCO 2007, Abstract 8020.
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TTIII plus bortezomib
Barlogie B, et al, ASCO 2007, Abstract 8020.
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Alternating bortezomib and dexamethasone as
induction regimen in younger MM patients
End of Induction Treatment (n40)
Best Response Ever Achieved (n40)
ORR 77.5
ORR 82.5
Rosinol L, et al, ASCO 2007, Abstract 8024.
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Alternating bortezomib and dexamethasone as
induction regimen in younger MM patients
Thrombocytopenia
Neutropenia
Peripheral Neuropathy
Skin
Grade 1
Gastrointestinal
Grade 2
Grade 3
Fatigue
Liver
0
100
80
Percent
Rosinol L, et al, ASCO 2007, Abstract 8024.
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Characteristics of patients relapsing after
autologous stem cell transplant
Mahmood ST, et al, ASCO 2007, Abstract 8022.
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Mel-based autotransplants for MM

• Retrospective analysis of 2836 transplant
  patients identified 5 factors that could
  influence outcomes
• Type of treatment (tandem transplant or not)
• Presence of cytogenetic abnormality
• High ß2-microglobulin
• Low albumin
• Low platelet counts

Pineda-Roman M, et al, ASCO 2007, Abstract 8043.
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Reduced intensity conditioning

• 32 patients with relapsed/refractory MM
• 19 patients with HLA-identical sibling donor
• 5 patients had disease progression
• 4 patients in complete remission
• 5 patients in PR or VGPR
• 13 patients with no HLA-identical donor
• 11 patients had disease progression
• Overall, 6 patients died from treatment-related
  mortality (incidence, 33)

Mohty M, et al, ASCO 2007, Abstract 8045.
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Multiple Myeloma Update from the American Society
of Clinical Oncology (ASCO) 43rd Annual Meeting

• Transplantation
• Discussion

Featuring
Nikhil Munshi, MD Dana-Farber Cancer
Institute Boston, MA
S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN
Moderator
Richard Lutes, MD
18
Multiple Myeloma Update from the American Society
of Clinical Oncology (ASCO) 43rd Annual Meeting

• Treating Relapsed/Refractory Disease

Featuring
Nikhil Munshi, MD Dana-Farber Cancer
Institute Boston, MA
S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN
19
Pegylated doxorubicin (PLD) and bortezomib vs
bortezomib alone
According to IMWG 2006 criteria. Harousseau JL,
et al, ASCO 2007, Abstract 8002.
20
Pegylated doxorubicin (PLD) and bortezomib vs
bortezomib alone
Overall survivalMedian follow-up time 14 mo
100
PLD Bortezomib
80
60
Percent of Subjects Alive ()
Bortezomib
40
20
0
Time (d)
Harousseau JL, et al, ASCO 2007, Abstract 8002.
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Effect of prior thalidomide treatment on efficacy
of pegylated doxorubicin (PLD) and bortezomib
Treatment by subgroup (IMiD exposed, IMiD naïve)
interaction test from the Cox model. Sonneveld P,
et al, ASCO 2007, Abstract 8023.
22
Effect of prior thalidomide treatment on efficacy
of pegylated doxorubicin (PLD) and bortezomib
According to IMWG criteria.Sonneveld P, et al,
ASCO 2007, Abstract 8023.
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Factors predictive of outcome in patients treated
with bortezomib, melphalan, prednisone, and
thalidomide (VMPT)
Age 65 years
Response PR rate
PR
65 years
Proportion of Patients
Proportion of Patients
P0.02
P0.19
Months
Months
Palumbo AP, et al, ASCO 2007, Abstract 8048.
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Factors predictive of outcome in patients treated
with bortezomib, melphalan, prednisone, and
thalidomide (VMPT)
?2-microglobulin
Deletion (13)
?2m Del (13)
Proportion of Patients
Proportion of Patients
No Deletion
?2m 3.5 mg/dL
P0.98
P0.06
Months
Months
Palumbo AP, et al, ASCO 2007, Abstract 8048.
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Multiple Myeloma Update from the American Society
of Clinical Oncology (ASCO) 43rd Annual Meeting

• Novel Agents

Featuring
Nikhil Munshi, MD Dana-Farber Cancer
Institute Boston, MA
S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN
26
Tanespimycin bortezomib in relapsed/refractory
MM

• Tanespimycin (17-AAG/KOS 953) disrupts heat shock
  protein 90 (hsp90), a molecular chaperone that
  transports proteins critical for MM growth,
  survival, and drug resistance
• Phase I dose escalation study in 49 patients
• 7th dose level reached so far
• Combination treatment was well tolerated
• Combination treatment resulted in inhibition of
  hsp90 and proteasome activity

Richardson PG, et al, ASCO 2007, Abstract 3532.
27
Phase I evaluation of carfilzomib (PR-171) in
hematologic malignancies

• Carfilzomib is a novel irreversible proteasome
  inhibitor
• Promotes 80 proteasome inhibition in the blood
• Dose-limiting toxicities
• Myelosuppression cyclic reversible
  thrombocytopenia and neutropenia
• A first dose effect has occurred at doses 20
  mg/m2 and heralds rapid decline in M-protein
• Objective responses have been observed at doses
  of carfilzomib ranging from 11 mg/m2 to 27 mg/m2
• Rapid onset of response (
• Responses are durable (4 to 9.5 months)
• Responses noted in bortezomib and IMiD failures
• Stable disease for 1 year

Stewart KA, et al, ASCO 2007, Abstract 8003.
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Multiple Myeloma Update from the American Society
of Clinical Oncology (ASCO) 43rd Annual Meeting

• Novel Agents
• Discussion

Featuring
Nikhil Munshi, MD Dana-Farber Cancer
Institute Boston, MA
S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN
Moderator
Richard Lutes, MD
29
Multiple Myeloma Update from the American Society
of Clinical Oncology (ASCO) 43rd Annual Meeting

• Final Thoughts

Featuring
Nikhil Munshi, MD Dana-Farber Cancer
Institute Boston, MA
S. Vincent Rajkumar, MD Mayo Clinic Rochester, MN
Moderator
Richard Lutes, MD