Hello Stewart, Sorry to be replying so late. I have been quite busy with work and life in general.
Thank you for your kind words. I will send you part one. Yes, I am planning to contact Dr. Lipton and have a similar good conference in Toronto. I hope to be able to share details shortly. Cheers and all best wishes, Cheryl --- In [email protected], "Stewart F. Sklar" <[EMAIL PROTECTED]> wrote: > > Cheryl-Anne > > What a wonderful synopsis of the > seminar. I did not receive Part 1, could you > kindly email it to me. I see there will be a > Montreal and Toronto meeting in January. Will the > Toronto meeting be similar in nature, i.e. held > at a hospital (PMH) with perhaps Dr. Lipton and > other specialists? Thank you for your continuing > good work and say hello to Suzan for me. > > At 10:11 PM 10/11/2005, you wrote: > >Hello All, > > > >As promised here is part II > > > >Before getting into part II I did want to > >mention another milestone that was celebrated at our meeting. > > > >We all signed a card and celebrated Suzan > >McNamara's birthday. A significant date for us > >all - since it was also the date 6 years ago > >that Suzan received the word from Novartis regarding the petition. > > > >Dr. Laneuville spoke to us about a CML registry > >that has been approved for Canada. This will be > >quite helpful to all of us as information on > >every patient will be entered into the database > >- blinded of course. All sorts of information > >will be tracked, for instance a Hem/Onc could > >query the data for all patients with low Hgb to > >determine if it is of any prognostic value. As > >you can imagine lots of information could be > >tracked and queried. Hopefully we'll hear more about this in the future. > > > >Now for Dr. Ravandi's part of the talk. > > > >Most of my notes are from the oncology > >conference he spoke at here in Montreal the day > >before meeting with us, but then again, he > >presented much of the same thing. If anyone who > >attended wants to add anything here, please feel free to do so. > > > >Dr. Ravandi also covered the history and origin > >of CML, and presented more data from the IRIS > >trial and the from information at MDACC. > > > >Dr. R. spoke about BCR ABL: > >It is a tyrosine kinase oncoprotein > >Auto and substrate phosphorylation > >Highly plastic structure > >"open" active versus "closed" autoinhibited > >state ( IM binds only to the active form) > >State regulated intra-and extra-molecularly > > > >In speaking about Gleevec - Dr. R. said: > >other kinases inhibited by IM are: > >ABL > >Bcr-Abl > >PDGFRâ > >c-Kit > > > >IM in the Phase I trial > > > >With 25-85 mg/day - only 1 patient out of 10 > >achieved a CHR (complete hematological remission > >- meaning blood counts were alright) > >140-250 mg/day- 10 patients out of 19 (53%) > >achieved CHR and 2 patients out of 19 (11%) achieved CCR > >300-1000 mg/day - 53 patients out of 54 (98%) > >achieved CHR and 29 (54%) patients out of 54 achieved cytogenetic response > >17 (31%) patients of the 54 achieved Major cytogenetic response > >No MTD (maximum total dose/day) was reached. > > > >He also covered the results of the IRIS trial, > >which was covered already by Dr. L. > > > >Dr. R. presented data on survival with IM in > >newly dxed CML comparing results with IRIS to MDACC > > > >IRIS had 553 patients and 51 months out - ~ 95% were still alive > >MDACC had 247 patients and ~ 98% were still alive. > > > >He showed data that was presented at ASH last > >year showing BCR-ABL levels continue to decrease > >with IM therapy in CP CML (28 pts on IRIS study Rx with IM 400 mg/d > > > >12 mos median log reduction was 3.0 and 46% had > >a 3 log or better and 4% had a 4 log or better reduction > >24 mos median log reduction was 3.4 and 68% had > >a 3 log or better and 7% had a 4 log or better reduction > >36 mos median log reduction was 3.9 and 71% had > >a 3 log or better and 32% had a 4 log or better reduction > >42 mos median log reductions was 4.2 and 71% had > >a 3 log or better and 54% had a 4 log or better reduction > > > >Looking at IM 400mg versus 800 mg (presented at ASH 2004 also) > >Of 175 patients chosen for the higher dose, 156 > >achieved Complete cytogenetic response > >of the 50 patients chosen for the lower dose 39 achieved CCR > > > >It is important to note that this was not a > >randomized trial. That is why the Gleem trial > >is happening in Canada, as a randomized trial is > >needed to prove the higher dose strategy/theory. > > > >The RIGHT study looked at various doses of IM - 300mg, 400mg, 600mg and 800mg > > > >It had the following endpoints: > >Primary: Percent of patients achieving molecular response > >Secondary: time to hematologic response, > >cytogenetic response, and complete molecular response > > - percent of patients with undetectable BCR-ABL transcripts at 12 mos > > - Safety > > > >Interestingly this study also showed the level > >of non compliance (as it were) in that it showed > >actual dose of IM over time. In the first 3 mos > >all patients were completely compliant at 3 mos > >- 36 patients were still at 800mg, 8 were at > >600mg and 3 were at 400mg, by 9 mos, 15 were at > >800mg, 5 were at 600mg and 5 were at 400mg, by > >12 mos, 7 were at 800mg, 1 was at 600mg and 3 was at 400mg. > > > >The results of the trial showed that 7 of the 11 > >patients who stayed at the 800mg dose achieved > >either a 3 log reduction or better and all 7 > >also achieved undetectable. So I guess there is > >something to be said about compliance! > > > >He spoke about mechanisms of "resistance" to IM (Bcr-Abl mediated or not) > > - Patient not taking drug > >- ABL point mutations going to conformation > >change of ATP binding site or modulators > >- Increase in BCR-ABL, showing BCR-ABL kinase activity > >- Metabolic, PK, drug interactions MDR clonal evolution > >- ? other kinases - VEGF, mTOR, src > >- CML no longer the main problem > > > >Speaking about AMN107: > > > >Showing the molecular structure he stated that > >AMN107 has a better interaction between ABL > >binding - improves the affinity of BCR-ABL to bind with AMN107. > > > >The conclusions from the Phase I trial of AMN107 are: > >Hematologic response rates >50% in AP and BP > >Cytogenetic responses in AP and BP > >No DLT (dose limiting toxicity) found > > Well tolerated up to 1,200 mg daily > > Rare liver, skin, or marrow AE's (adverse events) > > > >He spoke about Dasatinib - reviewing Talpaz's work presented at ASH last year: > > > >Of the 10 patients in BP, 50% achieved CHR, 80% achieved MHR > >Of the 32 patients in AP/ALL 28% achieved CHR, 69% achieved MHR > > > >In the same group of CML AP/BP the CG response was as follows: > >AP - 40% achieved CyR, 30% achieved CCyR, and 10% achieved PCyR > >BP - 56% achieved CyR, 10% achieved CCyR, and 16% achieved PCyR > > > >Of the most commonly reported non hematologic responses: > >Elevated ALT (28%) > >Elevated Creatinine (23%) > >Diarrhea (18%) > >Paresthesia (10%) > >Headache (10%) > >Nausea (5%) > >Peripheral edema (5%) > >Pleural Effusion (3%) > >GI Hemorrhage (0) > >These were of low grad 1 - 2 > >Note: we have heard more about pleural effusion > >in the current trials, so it will be interesting > >to see how this gets updated at this years ASH. > > > >He spoke about other things in the works such as > >Vaccines and things, but only briefly so. I > >think I'll get much more information at ASH. > > > >We finished off by presenting Dr. Ravandi with a > >Moose so he could tell all his friends he went Moose hunting in Canada. > > > >I have to tell you this though, as I mentioned > >he had presented to a bunch of oncs the day > >before, he mentioned he got much better > >questions from our patient audience than from > >the docs that he presented to. He was very > >impressed with our level of knowledge. > > > >We thoroughly enjoyed his company. > > > >Stay tuned for big news on more meetings coming in the future. > > > >Cheers, > >Cheryl-Anne > > > > > > > > > > > >New! Sign up for local CML support group > >meetings in your local community at > ><http://cml.meetup.com>http://cml.meetup.com > > > >Apply for Commercial Real Estate loans online > >and submit your deal to dozens of hungry lenders > >in just minutes. Loan programs for all types of > >business and commercial real estate. 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