An Update on the Treatment of Multiple Myeloma

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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.

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Myeloma Products of the malignant PC
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Myeloma Target Organs
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For difficult cases Serum Free Light Chains
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Plasma Cell Disorders Change over Time
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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

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Results following BMT - TOH
N 202 patients
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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

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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
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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

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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
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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?

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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
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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
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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
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Transplantation for MM 1 vs 2 autoPBSCT
Attal et al NEJM 3492495, 2003
Moreau et al Blood 107397, 2006
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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
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Transplantation for MM RIC alloPBSCT
Bruno NEJM 3561110, 2007
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Transplantation for MM RIC alloPBSCT
Bensinger, Frontiers in Bioscience 124384, 2007
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Transplantation for MM TMI
Wong BBMT 12306, 2006
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Treatment Spread out or all at once?
Barlogie et al NEJM 3541021, 2006
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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
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Treatment Spread out or all at once?
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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

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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

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Summary