4 replies to this topic

[ChrisC]

I feel that the last line is the main point, :

"We strongly suggest to capture baseline ABI, biochemical risk factors and to monitor these parameters regularly throughout therapy of CML."

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http://www.cancernet...e/10165/2142368

Nilotinib Associated With Increased Peripheral Artery Disease Rate in CML

Both a retrospective cohort analysis and a prospective study found higher rates of peripheral artery occlusive disease (PAOD) among patients with chronic myeloid leukemia (CML) who received nilotinib than in those who received imatinib. Both new studies were published online ahead of print on April 5 in Leukemia.

Previous reports on PAOD and nilotinib treatment in chronic-phase CML patients suggest a frequency of the arterial disorder of between 1.2% and 12.5%. "However, all previously published articles are limited by the description of only clinically manifest PAOD without screening of asymptomatic patients and without prospective monitoring," wrote authors of the prospective report, led by Theo D. Kim, MD, of the Charité-Universitätsmedizin Berlin in Germany. The group prospectively screened all chronic-phase CML patients at one institution between August 2011 and November 2012, using the ankle-brachial index (ABI) and duplex ultrasonography.

The study included 159 patients, some of whom were also included in other CML trials, such as ENESTnd. Of the total cohort, 54 patients were on first-line imatinib; 33 were on first-line nilotinib; 33 had previous imatinib exposure and were on second-line nilotinib; 25 had previous nilotinib and were on another therapy, considered "post-nilotinib"; and 14 were nilotinib-naïve patients not receiving imatinib.

ABI was obtained in 129 of the 159 patients (81%), and a pathological ABI indicating PAOD was seen in 24 of 129 (18.6%). There were higher rates of pathological ABI in nilotinib-treated patients than others. Only 6.3% of first-line imatinib patients had pathological ABI, compared with 26% of first-line nilotinib and 35.7% in the second-line nilotinib patients. In the post-nilotinib group, the rate was 16.6%, and 12.5% in the nilotinib-naïve group.

Both the first- and second-line nilotinib groups' rates of pathological ABI were significantly higher than the imatinib group (P = .0297 and .0029, respectively). PAOD that was clinically manifest, defined as "typical peripheral ulcerations or an acute event of PAOD," were found in five patients, all in the first-line, second-line, or post-nilotinib groups. The relative risk for PAOD defined by ABI was 10.3 for patients on first-line nilotinib vs first-line imatinib, a risk the researchers described as "remarkable."

The other analysis, a retrospective cohort study, painted a slightly different picture of PAOD and nilotinib, though the increased risk vs imatinib remained clear. That cohort included a huge number of chronic-phase CML patients: 533 with no tyrosine kinase inhibitor (TKI) treatment; 556 treated with nilotinib; and 1,301 treated with imatinib.

The nilotinib-treated patients had an exposure-adjusted risk for PAOD of 0.9 vs the -naïve patients, while the imatinib-treated patients had a risk of 0.1 compared with the -naïve cohort. A multivariate analysis showed that while nilotinib did not change the PAOD risk vs no , imatinib lowered the risk significantly, and nilotinib was associated with higher overall rates of PAOD than imatinib. The authors, led by Frank Giles, MD, of the National University of Ireland, Galway, concluded that patients initiating therapy for CML should undergo risk factor assessment for PAOD.

Dr. Kim and colleagues also agreed, concluding: "We strongly suggest to capture baseline ABI, biochemical risk factors and to monitor these parameters regularly throughout therapy of CML."

[Badger]

Thanks, but I have enough to worry about.

[ChrisC]

You are right, of course. This is what your onc is supposed to be informed about.

[pamsouth]

@ ChrisC; 

>This is what your onc is supposed to be informed about.<<

       Unfortunatly I have found even among leading CML Specilist, they are perhaps less informed than the board, or perhaps unwilling to share, or admit.  Sometimes, if I quote something from the board or a link to a CML study or report, the doc will say "well that is a small percent or that I am miss informed".  Several months ago a CML Specialist said Gleevec would become generic 2013, I said no I belive it is 2015.  Other little exchanges I have had with more than 1 specialist, makes me wonder if they are so.. uninformed, or not willing to share for whatever reason.  Perhaps they are just playing it safe, going by the standard protocol to protect their selves.  Maybe the drug companies/sales, down play the side effects. 

I think we still live in a day when Dr/Specialist, like us to be somewhat or only barely informed / not challenge them.  After all these drugs are pushed thru with short trials and a lot unknown risks.  It makes me uneasy to think we are in reality "the clinical trial", sometimes with little choice, given variables; of the Doctor/Insurance/Billing, & financial repsonsiblites which may be more for some than others. 

We do have the patient bill of rights.  But than in reality unless you have a strong advocate for you, it may not always work or you may not have a say or choice in treatment/dosage.  So do we really have a choice of TKI drugs or dosage & how well informed to the doctor make us, how much trust do we give them with our lives?? I remember a previous hematologist making it sound so easy, like a peice of cake, to change or jump around on TKI's.  To refuse to change drugs or challenge your doc is uncomfortable and changing doctors is in itself stressful.

Having said all that, let me not to forget to say "I am thankful that I was diagnosed in 2005, after Gleevec had become a patent in 2001, (I believe) with some data, and a much better drug, than what was previously avaiable.  However after meeting many others with chronic disease, we seem to have one think in common.  When diagnosed the doctors say what great drugs and a cure right around the corner, only to realize years later, they tell everyone that, knowing these drugs are far from a cure and a cure is not profitable, just like in many other chronic disease, that have been around for an eternity.

Diagnosed with CML 2005 and still on Gleevec at age 65 years.

The above is only my humble opinion and subject to change. 

[ChrisC]

Yes, you are right in feeling that we can benefit by being informed — this is why I posted this, along with my comment: "I feel that the last line is the main point, :'We strongly suggest to capture baseline ABI, biochemical risk factors and to monitor these parameters regularly throughout therapy of CML.'" I feel that having this information may help us get tested in good time when taking Tasigna, or especially when being switched to Tasigna. However, some folks prefer to leave it to their onc to know what is best, and I agree with that too, since that is less stressful for them, and stress is a major factor in our lives. Basically, however we choose to approach our situation and our treatment, that is correct for each of us individually and thus is to be supported : )