Multiple Myeloma Support Group
Hamilton & District
Hamilton, Ontario, Canada


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Saturday, September 8, 2007

 

 

††††††††††††††††††††††††††††††† ††††††††††††††† ††††††††††††††† MEETING

 

 

Lori advised that it is becoming increasingly difficult to transport old cell phones across the Border.Therefore, the MM Support Group will not accept them until further notice.

 

Lori and Marnie will be attending the Myeloma Today & Tomorrow: Progress & Challenges Seminar on Saturday, September 15, 2007, at the London Convention Centre.For those who may be interested in attending, there are pamphlets at the back.

 

The 5 K Walk will take place in Toronto on Saturday, October 14, 2007.

 

Lori introduced the speaker, Dr. Tom Kouroukis, his topic covered New and Emerging Therapies in Myeloma.

 

IMPORTANCE OF CLINICAL TRIALS

 

Clinical Trials provide improvement of outcome.

There are different categories.

It is important for the individual to be aware of these differences before entering any study.

The steps include††††††††††† Preclinical - usually takes place in a test tube.

††††††††††††††††††††††† ††††††††††† Phase I - toxicity study

††††††††††††††††††††††† ††††††††††† Phase II - Dosage & Schedule, Benefits & Failure

††††††††††††††††††††††† ††††††††††† Phase III - Comparative

††††††††††††††††††††††† ††††††††††† Phase IV - Marketing & unusual toxicities,Post Marketing††††††† ††††††††††††††††††††††† ††††††††††† †††††††††††††††††††Surveillance

 

NEW THERAPIES

 

Proteasome Inhibitors

IMiDíS

Antibody - Immune Therapy

Other Agents

 

PROTEASOME

 

All cells have proteasome . Proteasome are needed to recycle used proteins.Blocking the proteasomefunction leads to cell death.Certain cells are more sensitive to proteasomeinhibition compared to others.It took three Scientists, 30 years to figure this out.Ubiquitin-Pro Pathway is the formula these Scientists discovered.It is a very efficient system.

 

BORTEZOMIB (Velcade)

 

- first proteasomeinhibitor on the marked

- Pivotal Phase III study showed that it was better than Dexamethasone alone in relapsed/refractory myeloma.

 

APEX STUDY OVERVIEW

 

- randomized study that led to approval of Velcade

- 58% improvement with Velcade than with Dex alone

- fairly well tolerated

- blood counts generally go down but are quick to bounce back

 

BEYOND BORTEZOMIB ALONE

 

- combinations - next phase

- Bortezomib - Cyclophosphamide-Steroids

- Bortezomib - Melphalan-Prednisone

 

NEW PROTEASOME INHIBITORS

 

- PR-171 is being studied

- isolated from a bacteria

- better inhibition

 

No study has taken place to examine the use of Velcade as a maintenance program. Therefore, it is not available nor is it covered for a second time in Ontario when funded by the Government.If participating in a study it may be available a second and third time.

 

IMMUNOMODUATORY DRUGS - THE IMiDíS

 

- Thalidomide

- Lenalidomide - Revlimid

- Others - in development - even more potent

 

THALIDOMIDE

 

- originally marketed in Europe

- sedative and anti emetic activities

- associated with birth defects and neuropathy - withdrawn from market

- FDA approved for use with Leprosy

- approved May 2006 use with Myeloma combined with Dex

- approved after failure of standard therapies is Australia, New Zealand, Turkey & Israel

 

- original observation of a possible benefit took place in 1999

- subsequent, additional studies followed which led to combinations with other drugs

- Toxicities - dose and duration dependent

††††††††††† ††††††† - somnolence

††††††††††† ††††††† - constipation

††††††††† ††††††††- peripheral neuropathy

††††††††††††††††††† - DVT/PE

††††††††††††††††††† - rash

††††††††††††††††††† - Teratogenicity - fertility checks frequently

 

MECHANISM OF ACTION

 

- Anti-angiogenesis - blocks the form of new blood vessels

- Immunomodulatory properties - decreases toxicity, enhances potency

- Anti-tumour/ Apoptosis activities

 

LENALIDOMIDE / REVLIMID

 

- Phase I Study - results - best dose 25mgd

- Phase II Study - 40% response rate in relapsed patients - 1 to 3 responded

- Phase III Study - random and double blind

††††††††††† ††††††††††††††††† - placebo matched the appearance of Revlimid

††††††††††† ††††††††††††††††† - Physician and patient unaware of which was being taken

††††††††††† ††††††††††††††††† - huge benefit and improvement with length of keeping Myeloma

††††††††††††††††††††††† ††††††† bay

††††††††††† ††††††††††††††††† - some new side effects were noted

- New Patients - response rates of 90%

††††††††††††††††††††††††† - fast track through FDA

††††††††††††††††††††††††† - first approved for MDS - Myelodysplastic Syndrome

††††††††††† ††††††††††††† - approved July 2006 for Myeloma use with Dex

††††††††††† ††††††††††††† - approved in Europe, July 2007

 

ANTI-BODY IMMUNE THERAPY

 

- cell surface targets

- core of immune system B cells - proteins stick to bad cells

- immune surveillance - immune system kills bad cells when they are noticed

 

SGN 40

 

- Phase I Study

- how much can you give

- relapsed patient

- start small and build to determine proper dose to stable disease

- side effects indicate break point combined with success of CD40

 

IL6

 

- Study coming to Hamilton - Interluken 6

- developed anti-body

- through Phases I & II

- Phase III coming here in January

- compared with Velcade

- examined alone and with an anti-body added

- first biological anti-body study here

- world wide participation

 

HEAT SHOCK PROTEINS

 

- HSP90 helps normal proteins fold properly

- functional by proper folding

- oral - CNF2024 - very new

- IV - 17-AAG - tested pre-clinical in mice

- relapsed patients - Phase I Study - stable disease

††††††††††††††††††††††† †††††††††††††††††††††††††††††††††† - minimal and partial response

 

OTHER AGENTS - HDAC INHIBITORS

 

- Histones are necessary for DNA coiling

- Histone de-acetylase (HDAC) can be over expressed by cancer cells

- affects gene transcription - decrease in tumour suppression genes

- LBH589 in relapsed Myeloma - tested heavily in all blood diseases

- Novel Therapies targeting MM cell in its bone marrow microenvironment

- targeting MM cell

- targeting BM microenvironment

- targeting MM cell & BM microenvironment

 

BONY DISEASE

 

- Pomegranate - standard for MM

- side effects or issues - Osteonecrosis of Jaw - infection with non-

healing

- Nephrosclerosis - scar tissue building up in the kidneys

- new dry - comparative trials ongoing

- D MAB (Denosumab)

- D MAB - anti-body

- blocks bone forming unit

- to stay healthy - break bone up then rebuild

- works in balance so there is no long term bone loss

- D MAB Benefits - doesnít sit in the bone

††††††††††††††††††††††††††††††† - may work against MM cell

††††††††††††††††††††††††††††††† - could improve bone health and block the MM cell

 

SUMMARY

 

Use of established agents in novel combinations.

Bortezomib, Thalidomide, Lenalidomide.

Deveopment of newer versions of established drugs.

Development of truly novel drugs.

 

Questions were taken and Lori thanked Dr. Kouroukis for coming.

 

Next meeting Saturday November 10, 2007 with Jodi Steele speaking.