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Multiple Myeloma Support Group |
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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 IMiD’S Antibody -
Immune Therapy Other Agents PROTEASOME All cells have
proteasome . Proteasome are needed to recycle used proteins. Blocking the proteasome function leads to cell death. Certain cells are more sensitive to
proteasome inhibition 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
proteasome inhibitor 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 IMiD’S - 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 - doesn’t 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. |