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An Update on the Treatment of Multiple Myeloma

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Myeloma is highly variable between patients, treatment must be tailored to the ... Velcade (Millenium, Ortho) Boronic acid; iv administered d1,d4,d8,d11 q21days ... – PowerPoint PPT presentation

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Title: An Update on the Treatment of Multiple Myeloma


1
An Update on the Treatment of Multiple Myeloma
  • Dr. Harold Atkins
  • Blood Marrow Transplant Program
  • The Ottawa Hospital
  • Center for Cancer Therapeutics
  • Ottawa Health Research Institute.

2
Myeloma Products of the malignant PC
3
Myeloma Target Organs
4
For difficult cases Serum Free Light Chains
5
Plasma Cell Disorders Change over Time
6
Principles
  • Treat when symptomatic
  • Myeloma is highly variable between patients,
    treatment must be tailored to the patient
  • elderly or young patients
  • light-chain disease
  • bone disease
  • amyloidosis
  • There are no one-size fits all treatment options.
  • Treatment options vary at different stages of the
    illness

7
Results following BMT - TOH
N 202 patients
8
New Agents - Bortezomib
  • Velcade (Millenium, Ortho)
  • Boronic acid iv administered d1,d4,d8,d11
    q21days
  • Mechanism blocks proteosome
  • Side-effects
  • Fatigue
  • Peripheral neuropathy
  • Orthostatic hypotension
  • Thrombocytopenia
  • Nausea
  • Licensed in Canada
  • Available by SAP
  • Cost but covered in some provinces

9
New Agents - Bortezomib
Vel Dex
Median PFS Vel 6.2 mo Dex 3.5 mo
Median f/u 22 months
APEX trial OS in bortezomib (N333) and
high-dose DEX (N336) arms OS in
non-randomized subset of DEX patients who crossed
over to bortezomib due to PD within 6 months of
study start (N113)
Richardson et al, Blood Preprint Aug 2007
10
New Agents - Thalidomide
  • Thalomid (Celgene)
  • imid daily oral dosing
  • Mechanism uncertain, multiple?
  • Side-effects
  • Drowsiness/somnolence/fatigue/mental fogginess
  • Peripheral neuropathy
  • Thrombosis
  • Constipation
  • Rash
  • Not licensed in Canada
  • Available by SAP
  • Cost

11
New Agents - Thalidomide
  • Newly Dx patients
  • n RR cR PD
  • ThalDex 99 61 4 2
  • Dex 100 41 0 5

ThalDex Dex
  • Relapsed and Refractory MM patients

Singal et al NEJM 3411565, 1999
Rajkumar et al, JCO 24431, 2006
12
New Agents - Lenolidomide
  • Revlimid (Celgene)
  • imid, chemically related to Thalidomide oral
    dosing
  • Mechanism of action uncertain,multiple
  • Side-effects
  • Neutropenia
  • Diarrhea
  • Thrombocytopenia
  • Rash
  • Fatigue
  • Deep-vein thrombosis (DVT)
  • Not licensed in Canada
  • Not available via SAP, only via trial.
  • Cost?

13
New Agents - Lenolidomide
  • Relapsed or refractory MM
  • N 102
  • 30 mg po daily x 21d q28 days

Median OS 26 mo
Median PFS 7.7 mo
Richardson et al, Blood 1083458, 2006
14
Treatment in the elderly patient with MM
IFM 99-06 Previously untreated elderly patients
with MM 65-75 yrs old n median OS MP 196
33.2 mo MPT 125 51.4 mo Mel(100)BMT 126 38.3
mo Median f/u 51.5 mo
Facon, Lancet 3701210, 2007
15
Transplantation for MM 1 vs 2 autoPBSCT
  • Previously unTx MM
  • upto 60 yrs old
  • 15 didnt finish Rx in single PBSCT arm
  • 22 didnt finish Rx in tandem PBSCT arm

Attal et al NEJM 3492495, 2003
16
Transplantation for MM 1 vs 2 autoPBSCT
Attal et al NEJM 3492495, 2003
Moreau et al Blood 107397, 2006
17
Transplantation for MM allo vs autoPBSCT
Probability of Survival after Hematopoietic Stem
Cell Transplants for Multiple Myeloma,
1998-2004 - by Donor Type -
Slide 51
SUM06_45.ppt
CIBMTR
18
Transplantation for MM RIC alloPBSCT
Bruno NEJM 3561110, 2007
19
Transplantation for MM RIC alloPBSCT
Bensinger, Frontiers in Bioscience 124384, 2007
20
Transplantation for MM TMI
Wong BBMT 12306, 2006
21
Treatment Spread out or all at once?
Barlogie et al NEJM 3541021, 2006
22
Maintenance Therapy in MM
  • Following a tandem autoPBSCT, patients were
    randomized to
  • n
  • No Rx 200
  • Pamid 196
  • PamThal 201

PFS
OS
Attal et al Blood, 1083289, 2006
23
Treatment Spread out or all at once?
24
Supportive care management
  • Bone disease
  • Bisphosphonates (Aredia, Zometa, Bonefos)
  • osteonecrosis of the jaw
  • Surgery
  • Localized Radiation Therapy
  • Pain Relievers
  • Anemia
  • Erythropoietic Agent (Eprex, Aranesp)
  • Transfusion

25
Supportive Care Management
  • Infections
  • Penicillin twice daily prevention
  • Immunization (Pneumovax, Prevnar,…)
  • Antibiotics for fever, respiratory symptoms
  • IVIG for recurrent serious infections
  • Early recognition and treatment of Shingles.
  • Kidney function
  • Dialysis
  • Blood Pressure Medication

26
Summary
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