CML Patient Meetings in Montreal and Toronto - A well attended success!

[Guest guest]

Hello Everyone,

During the weekend of January 28 and 29th we held two consecutive meetings,

one in Montreal and one in Toronto for CML patients, their families and

friends. Both meetings were very well attended. Below, I have provided a

synopsis of both meetings. Big thanks to both Novartis and Bristol Myers

Squibb for helping us defray the costs of these meetings. All funds secured

go to paying for costs directly related to the events. The Montreal meeting

was filmed by an expert film crew who volunteered their time for us and we

hope to put together a CD/DVD which we will make available to everyone. No

one involved in the planning/organizing of the meeting charged fees for

their services. We would also like to recognize the Marriott Eaton Centre

Hotel for offering us significant discounts allowing us to hold the event in

Toronto there.

A very special BIG THANK YOU to Annikim Comtois. She is a close friend of

my daughter who lives in Toronto and does event planning. She organized the

entire meeting for us in Toronto and stayed with us for the day, without

remuneration. She is a wonderfully talented young woman with a great deal

of enthusiasm for seeing the CML Society thrive. Thank you Annikim!

It has taken me a while to put these notes together as I have been working

for 21 straight days and away on business. Today being the first day I am

able to get around to posting this information.

Montreal:

Dr. Laneuville started off the meeting by providing a brief background on

CML, as we had quite a few new patients. Then he presented highlights from

ASH. He spoke about the results of the IRIS trial, as well as the

information from both the AMN 107 trials and the Dasatinib trials. I will

make a more extensive post on Dr. Laneuville's slides in another post. We

are always very grateful to have him with us. Dr. Laneuville is an

excellent source of information to us, and I am hoping we can post some of

his slides up on our site. Please check our website: www.cmlsociety.org for

more information

Suzan McNamara presented the IRIS information recalling that she was one of

the 454 patients enrolled in the study and:

..- IM study began in 1999 - 454 pts were enrolled

..- Late chronic phase CML - failed interferon therapy

..- At enrollment patients had an expected survival time of 2 yrs

The results to date show:

.. - 5 yr follow up data showed that 80% of the patients are still alive and

showed no progression rate over time

.. - Pts - achieved a major cytogenic remission at 3-12 months - 90% OS

..- Pts - could not achieve cytogenic remission - 71% OS

Suzan also presented about Quiescent cells and highlighted these points:

..- Quiescent cells are cells that are not dividing but still alive

..- Ph+ quiescent stem cells are insensitive to IM or Dasatinib

..- Our Ph+ (CML) quiescent cells are quite harmless until they awaken and

start dividing again

..- May hold a mutation or a mechanism to where they are insensitive

..- Stats have shown that if we do stop IM / Dasatinib relapse

..- Reason why we cannot stop IM or Dasatinib

..- Im and/or Dasatinib do not inhibit quiescent cells therefore they do not

eliminate our disease

Suzan's presentation also included some highlights from a study with Tessa

Holyoake on FTI - BMS 214662:

BMS-214662 Targets Quiescent Chronic Myeloid Leukaemia Stem Cells and

Enhances the Activity of Both Imatinib and Dasatinib

..- BMS-214662, a farnesyl transferase inhibitor or FTI

..- IM / Dasatinib synergized with BMS-214662

..- In vitro studies demonstrated that the combination had a greater effect

of killing the Ph+ quiescent stem cells <50%

..- Currently in Phase I clinical trials

I presented information on a study in Italy of 4 patients who went off of IM

therapy, 2 relapsed and 2 did not. The interesting thing was that the two

who did not relapse had prior therapy with IFN. This leads some

investigators to think that it is possible that IFN offers an immunological

response that may endure through IM therapy.

I also presented a re-cap of AMN 107 and Dasatinib.

Some of the salient points on AMN107:

..- In reviewing the material, I have learned that AMN107 requires a less

stringent topological fit to the ATP-binding pocket in the inactive

conformation of BCR ABL. Mutations in ABL, which change the shape of the

binding pocket, have less of an effect on AMN107 binding than on IM binding.

..- AMN107 has increased potency and selectivity for Abl in contrast to IM,

which is more selective in vitro for PDGFR, followed by KIT then by ABL.

..- AMN107 is about 25 fold more potent for ABL than IM.

..- AMN107 does not interact with other TK such as Src, FLT3, VEGFR, EGFR,

InsR, RET, MET, or IGFR.

..- AMN107 selectively induces apoptosis and inhibits proliferation of

primary leukemic cells and cells transfected with BCR ABL.

..- AMN107 inhibits proliferation and autophosphorylation of 32 of 33 BCR ABL

point mutants; the only exception is T315I

..- AMN107 is expected to offer an improved side-effect profile compared with

IM, which is most encouraging to many of us.

I'll post about Toronto's meeting in the next post.

Cheers,

Cheryl-Anne