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"Imatinib Discontinuation in Chronic Phase CML Doesn't Always Lead to Relapse"


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#1 ChrisC

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Posted 18 June 2013 - 09:01 AM

http://www.cancernetwork.com...imatinib-discontinuation-doesnt-always-lead-relapse


Imatinib Discontinuation in Chronic Phase CML Doesn't Always Lead to Relapse


Almost half of patients with chronic-phase chronic myeloid leukemia (CML) who discontinued imatinib(Drug information on imatinib) treatment did not relapse, according to results of a prospective study. Those who did relapse showed continued sensitivity to imatinib when treatment started again.

"Around 40% of patients who remain on imatinib for more than 5 years will have undetectable minimal residual disease (UMRD)," wrote investigators led by David M. Ross, MD, of Flinders Medical Center in Australia, online ahead of print on May 23 in the journal Blood. Almost all patients with detectable minimal residual disease who stop tyrosine kinase inhibitor (TKI) therapy show rapidly rising levels of BCR-ABL, this may not be the case for those with UMRD. The new study examined whether discontinuation of imatinib could still yield sustained treatment-free remission in 40 patients.

The analysis showed that 18 of 40 patients (45%) had no evidence of molecular relapse after a median follow-up of 42 months since imatinib discontinuation. The relapses that did occur tended to occur quickly: 15 of 22 happened with the first 6 months of discontinuation of therapy, with a median of 3 months. No patients died and none progressed to advanced phase disease. The treatment-free remission rate at 2 years was 47.1%. Seven of the relapses occurred later, between 6 and 27 months after imatinib discontinuation.

Of the 18 patients in treatment-free remission, 5 had detectable BCR-ABL in their blood on at least one occasion; all were detected below threshold levels for loss of major molecular response. "These findings highlight the importance of confirming molecular relapse on two consecutive tests," the authors wrote.

All patients who relapsed restarted imatinib treatment, all eight who lost major molecular response regained it after a median interval of 2 months.

An analysis of the risk factors for relapse among these patients showed that the duration of interferon-alfa treatment prior to imatinib was associated with relapse risk, as was the amount of time to achieve UMRD after switching from interferon to imatinib. Shorter duration of interferon treatment was associated with higher relapse risk, and a slower achievement of UMRD also correlated with higher risk.

"The finding that around 40% of chronic phase CML patients with stable UMRD on imatinib can stop treatment and remain in [treatment-free remission] is clinically important, and reproducible," the authors wrote. A previous French study showed a nearly identical rate of treatment-free remission in a similar cohort of patients, and patients do not appear to develop resistant disease or resistance to treatment upon discontinuation.

"On the basis of this study and other published studies we believe that a carefully monitored trial of imatinib withdrawal can be undertaken safely in selected CML patients," the authors concluded.

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Good to know :)

ChrisC


Be alert, but not overly concerned.

 

• Dx Oct. 22, 2008, WBC 459k, in ICU for 2 days + in hospital 1 week

• Leukapheresis for 1 week, to reduce WBC (wasn't given Hydroxyurea)

• Oct. 28, 2008: CML confirmed, start Gleevec 400mg

• Oct. 31, 2008: sent home when WBC reached 121k

• On/off, reduced dose Gleevec for 7 months

• April 2009: Started Sprycel 100mg

• Sept. 2009: PCRU 0.000

• Sept. 2011: after 2 years steady PCRU & taking Sprycel 100mg before bed, quit Sprycel (with permission)

• Currently: still steady PCRU, testing every 6 months 🤗

— Fatigue, hearing loss continue, alas, but I prefer to think it is all getting better!

 

 


#2 GerryL

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Posted 18 June 2013 - 06:39 PM

Hi Chris,

I put a link to Dr Hughes' presentation on here the other week. His comments seemed to indicate that once past the 2 years none of his test subjects had relapsed.

Thanks for the info about looking at two consecutive tests for evidence of relapse.

I've spoken with my doc and am looking to come off in mid November. My doc doesn't seem to have read much on stopping TKIs, I think he feels that if the drug is working why take a chance, so I need to make sure I have all the info.



#3 ChrisC

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Posted 20 June 2013 - 12:24 PM

Hi GerryL,

Good for you, I wish you all success!

It appears that there is a bit more recent activity in performing studies and publishing the results, which sometimes we come across before our doctors do

Here is a new one that is more age specific:

www.cancernetwork.com...cml-patients-shows-promise

Intermittent Imatinib for Elderly CML Patients Shows Promise

A phase II study found that an alternative imatinib(Drug information on imatinib) treatment schedule for elderly patients with chronic myeloid leukemia (CML) could be an effective way to reduce dosing requirements of the drug. The schedule of treatment involved 1 month on, 1 month off, and appeared to affect markers of residual disease but not overall and progression-free survival.

"With imatinib at the standard dose of 400 mg daily, 80% to 90% of patients are alive at 8 years, but only a small proportion of patients (about 5%) can discontinue the treatment without suffering a molecular recurrence," wrote investigators led by Domenico Russo, MD, of the University of Brescia in Italy, online ahead of print on May 15 in the journal Blood. "Thus, the great majority of responsive patients would be destined to continue the treatment indefinitely, at the same standard dose." To address attendant problems of treatment compliance and toxicity, Dr. Russo and colleagues conducted the single-arm phase II INTERIM study to investigate a 1-month-on, 1-month-off (following a 1-week, and then 2-week alternation schedule to ease into the new schedule) treatment schedule for imatinib in patients over the age of 65.

All patients in the study had been on imatinib for at least 2 years and were in stable complete cytogenetic response; a total of 76 patients were included in the study. The median duration of treatment at study entrance was 60 months, and 81% were on the 400-mg dose "in spite of the age and the long treatment duration," the authors wrote.

Thirteen patients (76%) lost cytogenetic response and molecular response, and all except one who was lost to follow-up regained both after resuming standard, continuous imatinib treatment. Six of those patients lost the response during the first 12 months, and the other seven lost it between the 13th and 27th month. Fourteen other patients lost major molecular response only, nine of whom resumed continuous imatinib therapy and regained major molecular response.

No patients in the study progressed to accelerated or blast phases of CML, though two patients died during the study, because of acute myocardial infarction in one and intracranial hemorrhage in the other. The estimated progression-free survival at 12 months was 100%, and 96% at 48 months. The toxicities reported all existed when patients enrolled in the study, and no patients reported new or more severe adverse events during the "on" months of treatment.

"The results of this study do not allow us definitively to conclude that intermittent treatment can be offered to optimal and stable responders, but opens a window to alternative treatment policies, even in the patients for whom a very deep molecular response cannot be achieved," the authors concluded.

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Interesting!

ChrisC


Be alert, but not overly concerned.

 

• Dx Oct. 22, 2008, WBC 459k, in ICU for 2 days + in hospital 1 week

• Leukapheresis for 1 week, to reduce WBC (wasn't given Hydroxyurea)

• Oct. 28, 2008: CML confirmed, start Gleevec 400mg

• Oct. 31, 2008: sent home when WBC reached 121k

• On/off, reduced dose Gleevec for 7 months

• April 2009: Started Sprycel 100mg

• Sept. 2009: PCRU 0.000

• Sept. 2011: after 2 years steady PCRU & taking Sprycel 100mg before bed, quit Sprycel (with permission)

• Currently: still steady PCRU, testing every 6 months 🤗

— Fatigue, hearing loss continue, alas, but I prefer to think it is all getting better!

 

 


#4 Trey

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Posted 20 June 2013 - 04:43 PM

The "pulsed therapy" for CML (alternating months on/off drugs) has not shown any promise.  It is a much better approach to take continuous lower dosage TKI drugs than pulse the drug therapy.  76% failure is not very good in the cited study. 



#5 ChrisC

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Posted 20 June 2013 - 08:40 PM

Good that now we know that, Trey, thanks. Let's hope that there are many more published studies that we can refer to when discussing possibly discontinuation of TKI treatment, under supervision of course It seems that folks are needing to bring in their own information about these studies to their oncs, yes?


Be alert, but not overly concerned.

 

• Dx Oct. 22, 2008, WBC 459k, in ICU for 2 days + in hospital 1 week

• Leukapheresis for 1 week, to reduce WBC (wasn't given Hydroxyurea)

• Oct. 28, 2008: CML confirmed, start Gleevec 400mg

• Oct. 31, 2008: sent home when WBC reached 121k

• On/off, reduced dose Gleevec for 7 months

• April 2009: Started Sprycel 100mg

• Sept. 2009: PCRU 0.000

• Sept. 2011: after 2 years steady PCRU & taking Sprycel 100mg before bed, quit Sprycel (with permission)

• Currently: still steady PCRU, testing every 6 months 🤗

— Fatigue, hearing loss continue, alas, but I prefer to think it is all getting better!

 

 


#6 GerryL

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Posted 23 June 2013 - 07:34 PM

It feels a bit like that for me.

A friend of mine decided to take a break from her Gleevec (with her doctor's approval) and she was also hoping to be able to stop altogether. Her CML appeared again at her six monthly test and she is now back on her Gleevec. But she was also only being tested quarterly whilst she was stopping. When she spoke with her doc about not getting tested more often, he told her that she didn't require monthly testing and 3 monthly was adequate.



#7 pamsouth

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Posted 23 June 2013 - 08:29 PM

That's what I keep saying to myself and doc, Chronic.  In the year I have that I have been test at IU every 3 month, my Fish & PCR range anywhere from 1% to 13 % .

My last FISH & PCR that were done 6/13/13 were both at 3% go figure.  At any rate I will be starting Sprcel at 50mg in a week or so. Staying at 50mg for a few months, not jumping  up right away, hope to never jump up.  If it doesn't work out, going back to Gleevec, been on it for 8 years.  Just worried about kidneys.  Gall Bladder stopped working in 2007, no gall stones, just didn't work right opening and shuting tube to release bile.  Now GFR on kidnesy at stage 3 for CKF.  Now is that from Gleevec,  diurectic, from being 65 years old, or all of the above don't know.  But feel like I am losing my organs one at a time.


PamSouth


#8 GerryL

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Posted 23 June 2013 - 10:17 PM

Hi Pam,

Best of luck with the Sprycel.






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