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Multiple Myeloma Update from the XIth International Myeloma Workshop IMW

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Title: Multiple Myeloma Update from the XIth International Myeloma Workshop IMW


1
Multiple Myeloma Update from the XIth
International Myeloma Workshop (IMW)
  • Welcome and Introduction

Featuring
Sagar Lonial, MD Winship Cancer Institute Emory
University Atlanta, GA
Meletios A.K. Dimopoulos, MD National and
Kapodistrian University of Athens Athens, Greece
Moderator
Thomas J. Burke
2
Multiple Myeloma Update from the XIth
International Myeloma Workshop (IMW)
  • Genetics

Featuring
Meletios A.K. Dimopoulos, MD National and
Kapodistrian University of Athens Athens, Greece
Sagar Lonial, MD Winship Cancer Institute Emory
University Atlanta, GA
3
Genetics IFM 99-02 study
Patients lt66 Years
No t(414), no del(17p), low ?2m
Other
Overall Survival
T(414) or del(17p), and high ?2m
Time (d)
Avet-Loiseau H, et al, IMW 2007, Abstract S1.5.
4
Multiple Myeloma Update from the XIth
International Myeloma Workshop (IMW)
  • Genetics
  • Discussion

Featuring
Meletios A.K. Dimopoulos, MD National and
Kapodistrian University of Athens Athens, Greece
Sagar Lonial, MD Winship Cancer Institute Emory
University Atlanta, GA
Moderator
Thomas J. Burke
5
Multiple Myeloma Update from the XIth
International Myeloma Workshop (IMW)
  • Upfront Therapy

Featuring
Sagar Lonial, MD Winship Cancer Institute Emory
University Atlanta, GA
Meletios A.K. Dimopoulos, MD National and
Kapodistrian University of Athens Athens, Greece
6
Melphalan/prednisone/thalidomide (MPT) vs
melphalan/prednisone (MP) in patients aged 75
years (IFM 01-01 trial)
Hulin C, et al, IMW 2007, Abstract S11.8.
7
Melphalan/prednisone/thalidomide (MPT) vs
melphalan/prednisone (MP) in patients aged 75
years (IFM 01-01 trial) (cont)
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, IMW 2007, Abstract S11.8.
8
Melphalan/prednisone/lenalidomide (MPR)
Above responses were obtained with the maximum
tolerated dose (MTD) of lenalidomide 10 mg/day
for 21 days, melphalan 0.18 mg/kg for 4 days, and
prednisone 2 mg/kg for 4 days monthly.
Palumbo A, et al, IMW 2007, Abstract PO-717.
9
Long-term follow-up of bortezomib/
adriamycin/dexamethasone (PAD)
Popat R, et al, IMW 2007, Abstract PO-725.
10
Bortezomib plus melphalan/prednisone vs
melphalan/prednisone VISTA trial design
  • Eligibility Criteria
  • Previously untreated MM
  • Not eligible for HDT/SCT
  • Presence of measurable disease
  • Karnofsky performance status score 60

Melphalan/ Prednisone
Key endpoints Time to progression Survival
Randomization 11 n680
Bortezomib/ Melphalan/ Prednisone
Completed accrual
Information from clinicaltrials.gov and
investor.millennium.com.
11
Phase I/II trial of lenalidomide/bortezomib/dexame
thasone
MTD not yet achieved.
Richardson PG, et al, IMW 2007, Abstract PO-715
June 28, 2007 Press release from Millennium
Pharmaceuticals.
12
Multiple Myeloma Update from the XIth
International Myeloma Workshop (IMW)
  • Upfront Therapy
  • Discussion

Featuring
Meletios A.K. Dimopoulos, MD National and
Kapodistrian University of Athens Athens, Greece
Sagar Lonial, MD Winship Cancer Institute Emory
University Atlanta, GA
Moderator
Thomas J. Burke
13
Multiple Myeloma Update from the XIth
International Myeloma Workshop (IMW)
  • Transplantation

Featuring
Meletios A.K. Dimopoulos, MD National and
Kapodistrian University of Athens Athens, Greece
Sagar Lonial, MD Winship Cancer Institute Emory
University Atlanta, GA
14
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, IMW 2007, Abstract S7b.1.
15
Alternating bortezomib and dexamethasone as
induction regimen in younger MM patients (cont)
Thrombocytopenia
Neutropenia
Peripheral Neuropathy
Skin
Grade 1
Gastrointestinal
Grade 2
Grade 3
Fatigue
Liver
0
100
80
Percent
Rosinol L, et al, IMW 2007, Abstract S7b.1.
16
Tandem autologous vs autologous followed by
mini-allogeneic transplants
  • Three trials
  • French group (IFM 99-03 and IFM 99-04)
  • No difference in EFS
  • OS 59 months for auto-auto vs 35 months for
    auto-allo (P0.016)
  • Spanish group
  • No difference in EFS or OS
  • CR rate 11 in auto-auto group vs 33 in
    auto-allo group (P0.02)
  • US group
  • No difference in OS or PFS at 2 years
  • At 4 years, groups appeared to separate but no
    statistical differences except
  • Relapse rate 39 in auto-auto group vs 58 in
    the auto-allo group (P0.05)

Moreau P, et al, IMW 2007, Abstract S7b.2
Rosinol L, et al, IMW 2007, Abstract PO-809
Sahebi F, et al, IMW 2007, Abstract PO-810.
17
Single vs tandem transplant
P0.001
Bjorkstrand B, et al, IMW 2007, Abstract S7b.4.
18
Maintenance therapy after stem cell
transplantation
  • The role of thalidomide?
  • The role of bortezomib or lenalidomide?

19
Multiple Myeloma Update from the XIth
International Myeloma Workshop (IMW)
  • Transplantation
  • Discussion

Featuring
Meletios A.K. Dimopoulos, MD National and
Kapodistrian University of Athens Athens, Greece
Sagar Lonial, MD Winship Cancer Institute Emory
University Atlanta, GA
Moderator
Thomas J. Burke
20
Multiple Myeloma Update from the XIth
International Myeloma Workshop (IMW)
  • Treating Relapsed/Refractory Disease

Featuring
Meletios A.K. Dimopoulos, MD National and
Kapodistrian University of Athens Athens, Greece
Sagar Lonial, MD Winship Cancer Institute Emory
University Atlanta, GA
21
Lenalidomide/dexamethasone vs placebo/dexamethason
e (MM-010 study)
Anagnostopoulos A, et al, IMW 2007, Abstract
PO-661.
22
Pegylated liposomal doxorubicin (PLD) and
bortezomib vs bortezomib alone
According to IMWG 2006 criteria. Nagler A, et
al, IMW 2007, Abstract PO-625.
23
Pegylated liposomal doxorubicin (PLD) and
bortezomib vs bortezomib alone (cont)
Overall survival Median follow-up time 14 mo
100
PLD Bortezomib
80
60
Percent of Subjects Alive ()
Bortezomib
40
20
0
Time (d)
Nagler A, et al, IMW 2007, Abstract PO-625.
24
Multiple Myeloma Update from the XIth
International Myeloma Workshop (IMW)
  • Treating Relapsed/Refractory Disease
  • Discussion

Featuring
Meletios A.K. Dimopoulos, MD National and
Kapodistrian University of Athens Athens, Greece
Sagar Lonial, MD Winship Cancer Institute Emory
University Atlanta, GA
Moderator
Thomas J. Burke
25
Multiple Myeloma Update from the XIth
International Myeloma Workshop (IMW)
  • Novel Agents

Featuring
Meletios A.K. Dimopoulos, MD National and
Kapodistrian University of Athens Athens, Greece
Sagar Lonial, MD Winship Cancer Institute Emory
University Atlanta, GA
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, IMW 2007, Abstract PO-615.
27
Perifosine (KRX-0401)
  • Oral, signal transduction modulator
  • Inhibits Akt and activates Jnk
  • Current trials
  • Phase I/II trial with bortezomib in patients with
    relapsed/refractory MM
  • Phase I and phase II trials with lenalidomide and
    dexamethasone in patients with relapsed/refractory
    MM

Richardson PG, et al, IMW 2007, Abstract PO-608
Jakubowiak A, et al, IMW 2007, Abstract PO-606
Richardson PG, et al, IMW 2007, Abstract PO-607.
28
Carfilzomib (PR-171)
  • Carfilzomib is a novel irreversible proteasome
    inhibitor
  • Promotes gt80 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 (lt1 month)
  • Responses are durable (4 to gt9.5 months)
  • Responses noted in bortezomib and IMiD failures
  • Stable disease for gt1 year

Alsina M, et al, IMW 2007, Abstract PO-611.
29
Multiple Myeloma Update from the XIth
International Myeloma Workshop (IMW)
  • Novel Agents
  • Discussion

Featuring
Meletios A.K. Dimopoulos, MD National and
Kapodistrian University of Athens Athens, Greece
Sagar Lonial, MD Winship Cancer Institute Emory
University Atlanta, GA
Moderator
Thomas J. Burke
30
Multiple Myeloma Update from the XIth
International Myeloma Workshop (IMW)
  • Complications of Disease and Treatment

Featuring
Meletios A.K. Dimopoulos, MD National and
Kapodistrian University of Athens Athens, Greece
Sagar Lonial, MD Winship Cancer Institute Emory
University Atlanta, GA
31
Osteonecrosis of the jaw (ONJ)
  • Occurs as a result of long-term bisphosphonate
    treatment, frequently in MM patients
  • ONJ may occur more frequently in patients treated
    with zoledronate and pamidronate
  • Lesions should be biopsied to assess potential MM
    involvement
  • Osteoblast and osteoclast genes and proteins are
    significantly downregulated in patients with ONJ
  • Antibiotic prophylaxis before/after dental
    procedures appears to decrease the incidence of
    ONJ

Montefusco V, et al, IMW 2007, Abstract PO-1115
Cafro AM, et al, IMW 2007, Abstract PO-1116
Tacchetti P, et al, IMW 2007, Abstract PO-1117
Raje N, et al, IMW 2007, Abstract PO-1118 Gil R,
et al, IMW 2007, Abstract PO-1119.
32
Multiple Myeloma Update from the XIth
International Myeloma Workshop (IMW)
  • Complications of Disease and Treatment
  • Discussion

Featuring
Meletios A.K. Dimopoulos, MD National and
Kapodistrian University of Athens Athens, Greece
Sagar Lonial, MD Winship Cancer Institute Emory
University Atlanta, GA
Moderator
Thomas J. Burke
33
Multiple Myeloma Update from the XIth
International Myeloma Workshop (IMW)
  • Closing Remarks

Featuring
Meletios A.K. Dimopoulos, MD National and
Kapodistrian University of Athens Athens, Greece
Sagar Lonial, MD Winship Cancer Institute Emory
University Atlanta, GA
Moderator
Thomas J. Burke
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