Cheryl: Thank you for your hard work and wisdom. We need to focus on being alive and not the side-effects. Everything is attitude! Peace. Dave
>From: "Cheryl-Anne Simoneau" <[EMAIL PROTECTED]> >Reply-To: [EMAIL PROTECTED] >To: <[EMAIL PROTECTED]> >Subject: [CML] Long term survivability with IM - Long post >Date: Wed, 22 Sep 2004 09:37:18 -0400 > >Hello Folks, > > > >The abstract was pre-published in June I think, so some of the data might >be >familiar to you. It is a long paper and I have been going through it to >pick out the salient data that was all done through multivariate analysis. >This work compares two study groups, IM study 110 and 113 with historical >information collective over a 13 year period before IM. The results are >interesting, and although we sometimes complain of fatigue, bone pain and >other side effects, we are collectively doing much better than those >courageous troopers, our CML comrades from days gone by. We must remember >them and their struggles. > > > >Today in spite of our side effects we can think in terms of questioning >starting a family, staying at work, and planning for retirement. Not so >long ago these issues were replaced by just the daily struggles of being >able to make it from one day to the next. Yes, life isn't perfect but >funny >enough we are all well enough now to know life isn't perfect and to >question >why it isn't. > > > >Lately we've read about how doctors are shying away from the use of the >word >"cure". That isn't really so upsetting is it? CML is a part of our life, >and we are managing to live long and relatively better lives in spite of >it. >Maybe I am not so sure I want to talk in the terms of a cure either. I >like >me better now with CML than prior to my diagnosis. Some of the symptoms >and >side effects I endure today, might really have nothing to do with IM, maybe >it's just the aging process. The one thing I know about life, is that >nobody get's out of it alive, so maybe I shouldn't be looking for a cure. >I >am happy to sustain it as long as I can, and I am really happy to be here >in >this time and place where we can positively think about long term >survivability. > > > >This paper reflects many of us who have had and continue to have good >response with IM, and it also reflects those among us who did not have a >good response. This paper is important as it makes us realize the new >"gold >standard" in therapy approaches to CML. So, look at the rates and analysis >results for those who've had a good response with IM, that's the very least >the next drug must achieve. That's pretty powerful stuff! We are >witnessing the magic of the new drugs now in clinical trials and we are a >fortunate group to be part of this dynamic life sustaining break-through of >IM. > > > >I know many of us endure nasty side effects on our way to winning the >battle >over this disease, and there are many of us who must suffer through the >side >effects without the benefit of gain in reducing the burden of this disease. >Let's all hold on together - we are on the winning side of the war against >cancer! > > > >Cheers and good reading! > > > >Long term survival benefit and improved complete cytogenetic and molecular >response rates with IM in CML after failure with IFN. > > > >By: Kantarjian, Crotes, O;Brien et al MDACC > > > >Cheryl's synopsis: > > > >This is a clinical observation paper that reviewed the results of patients >from 2 Novartis-sponsored phase 2 pivotal study of CML after IFN failure. >Study 110 - 149 patients and study 113, 112 patients. This patient group >was compared with an historical group of 251 patients treated with >nonimatinib therapies. > > > >The median follow up time was 45 months, the major cytogenetic response >rate >was 73% and the complete cytogenetic response rate was 63%. The estimated 4 >year survival rate was 86%. > > > >Multivariate analysis for survival identified 3 key factors which would >have >independent poor prognostic significance: 1.) haematological resistance, >2.) >splenomegaly, 3.) lack of any cytogenetic response after 3 months of >therapy. Patients results could be divided into risk groups: 1.) good- no >adverse factors, 2.) intermediate (1 adverse factor), and 3.) Poor-risk (2 >-3 risk factors).- 12% of the patients in this group were in the poor-risk >factor. Based on these groupings the 4-year survival rates were: group 1 >(good) 96%, group 2 (intermediate), 86% and group 3 (poor) 49%. > > > >The 4 year cumulative major molecular response (as by Q-PCR and described >as >BCR-ABL/ABL at less than 0.05%) rate was 43% and complete molecular >response >rate (BCR-ABL undetectable) 26% for these two study groups. > > > >The results of the imatinib group were compared to the historical group. >Not surprisingly, the IM group was associated with a better 4-year survival >rate (86 % versus 43%), this survival rate advantage was confirmed by >multivariate analysis. > > > >Giving what has previously been studied and is highlighted below, the >following 5 questions are the subject of this analysis: > > > > (1) will CCR be sustained or even improved with long-term follow up, (2) >whether the low annual mortality rates will persists in later years (3) >whether a prognostic model, based on pre-treatment characteristics and >early >response to therapy, could accurately predict patients who ultimately >achieve complete cytogenetic responses (4) the incidences of major >molecular >(BCR-ABL/ABL ratios less than 0.05%) and complete molecular response (PCRU) >which predict excellent long-term prognosis and (5) the significance of >chromosomal abnormalities other than Ph. - These 5 questions are the >subject >of this analysis > > > > > > > > > >Key points of the paper: > > > >1.) key therapies in CML attempted to suppress the PH+ of the PH >related >BCR-ABL kinase activity to alter the natural course of the disease. > >2.) SCT - allo produced long-term (not the lack of the use of the word >cure) event-free survival rates of 30% to 80% and 1-year mortality rates of >5% to 50% (depending on patients age, donor status etc) > >3.) IFN therapy induced cytogenetic response rates of 30% - 70%, which >were complete (0% PH+ cells) in 5% - 30%. Median survival rates for IFN >was >5 - 7 years (9 years for patients in the "good" risk category). A complete >cytogenetic response rate on IFN was associated with 10-year survival rates >of 70% to 85% > >4.) IM has showed encouraging results in all three phases of CML (CP, >AP >& BP) after IFN failure, IM induced major cytogenetic response rates of 60% >and CCR rates of 40%. 18 month estimated freedom-from-progression and >survival rates of 89% and 95% respectively. > > > >Study groups > > > >IM group: study 110 - 149 patients and expanded study 113 (112) patients. >Entry criteria was IFN failure and adequate performance in Oncology group >scores, renal functions, cardiac function (those with New York Heart >Association grades 3 to 4 cardiac disease were excluded) Hydrea within 7 >days, IFN within 14 days, or other investigational agents within 28 days of >starting IM were not allowed. All patients had to be in chronic phase. > > > >Patients were given 400 mg orally of IM, dose escalation to 400 mg twice >daily was considered for patients who did not achieve CHR at least three >months of therapy, those who relapsed, or those who did not achieve a major >cytogenetic response after 12 months or those with a cytogenetic relapse. > > > >Response Criteria > > > >Based on the scale and lasting for at least 4 weeks: Complete response = >PH+ >of 0%, Partial = Ph+ 1%-34%, minor = Ph+ 35% to 90%. Major cytogenetic >responses included complete plus partial cytogenetic responses. > > > >Historical group: Patients in early CP and treated on institutional >protocols from 1982 until 1995 and whose disease subsequently progressed >while on IFN and in CP. Total of 251 patients, Median age 45 (range 19 >to >77 years), 110 patients were on Hydrea/Busulfan, 42 patients on HHT, 27 >patients on chemo combinations, 38 patients went to SCT, and other >treatments - 34 patients. > > > >Patients > > > >Median follow up time was 45 months for both study group 110 was 48 months >and for 113 it was 35 months. At the time of the last follow up, 230 of >the >261 patients (88%) were alive, 196 (75%) were in CP on IM and 31 patients >had died. > > > >Responses > > > >For IM: CHR (complete haematological response) - 96% in patients with >active disease, cytogenetic response was 79%, major cytogenetic response >was >73% and CCR was 63% . Interestingly there was a continued increase in the >cumulative major and complete cytogenetic response rates with therapy, even >after 2 years. In patients who had achieved only a minor cyto response >who later continued to improve to CCR were 62 - 76%. That rate decreased >to >only 10% in patients who still had a minor cyto response after 12 months. >Patients in a partial cyto response after 12 months still had a 73% >incidence of later achieving a CCR. Patients who only had a minor response >or no cyto response had worse estimated 4-year survival rates (70% to 79%), >when compared to those who had achieved better response rates (88% to >100%). > > > >74 of the 261 patients had dose escalations to either 800mg or 600mg. 23 >patients in the dose-escalation category, 16 (70%) improved their cyto >response to complete (n=9) partial (n-6) or minor (n=1) and were sustained >in 7 of the patients (30%) Among 28 patients treated for cyto >refractoriness, 16 (57%) improved their cyto response to complete (n-6) >partial (n-6) or minor (n_4) and were sustained in 7 (25%) patients. > > > >Among 23 patients treated for haematological resistance, 9 (39%) achieved a >CHR, 2 of them with cyto response (1 partial, 1 minor) and 5 patients (22%) >had a partial hem response. 5 patients are in sustained hem. response. > > > >Of the 261 patients - 196 (75%) remain alive in CP on IM, 31 have died, 34 >are alive in different CML phases or other therapies. Of the 31 who died, >27 died after discontinuation of IM, 4 during IM therapy. 18 patients have >died after disease progression to accelerated (n-5) or blastic (n-13), 13 >patients died of other causes (2 infections, e cardiac events, and 2 after >allo sct and 6 from other causes). > > > >Estimated 4 - year freedom-from-transformation rate was 80%, the estimated >4 >year progression-free survival rate was 86%. > > > >256 patients alive on IM at 3 months, 219 had evaluable cyto response, 142 >(55%) achieved a cyto response (complete, partial or minor) . The >estimated >4-year survival rates were 95% for those who had achieved a cr and 72% for >those who did not.. 4 year progression-free survival was better for CR >patients than not (93% versus 55%). > > > >246 alive at 6 months, 199 had evaluable CR and 112 (46% of total) had a >major cyto response. Estimated 4-year survival (95% versus 78%) and >progression-free survival (93% versus 65%) were better in patients with a >major response. > > > >Durability patients (4 were not followed up at MDACC) , 147 patients (93%) >continue to have durable complete (n=122) or partial (n-25) cr while 11 >(7%) >showed loss of major cyto. Among 26 patients with partial , 10 have lost >the response. 14 patients who achieved a minor cyto 9 (64%) have so far >shown loss. > > > >Comparison of survival with IM to previous historical experience - TO BE >CONTINUED ON MY NEXT POST - Later on today > > > >Cheers, > >Cheryl-Anne > > > ------------------------ Yahoo! Groups Sponsor --------------------~--> Make a clean sweep of pop-up ads. Yahoo! Companion Toolbar. Now with Pop-Up Blocker. Get it for free! http://us.click.yahoo.com/L5YrjA/eSIIAA/yQLSAA/8zSolB/TM --------------------------------------------------------------------~-> New! 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