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Needing Advice on Dasatanib Deescalation/Cessation.

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Disclaimer, I am writing for my Father, and he has ALL PH+, but this seems to be a great forum and figured I could hopefully be pointed in the right direction.  My Dad has been on Dasatanib 100mg, q.d, for 12 years.  2 months ago he had 2 heart blocks that caused lose of consciousness.  Pericardial and Pleural effusions showed up 2 weeks later.  Pacemaker was put in as A fib was starting as well.  BCR ABL has been at <.01 for 12 years, he did HYPER CVAD/ Dasatanib front line, and was one of the first to do so with ALL ph+.  He stopped Dasatanib after both pericardial and pleural effusions set in.  Has been off Dasatanib for 6 weeks.  BCR ABL went to .04 at 4 weeks.  then to .08 at 6 weeks.  He reinitiated 25mg of Dasatanib 3 days ago when we got the .08 results back.   

Thus so, I am very familiar with Dr. Clarke and all the amazing cessation docs in the UK who are working with CML, but we cannot find any that are working with ALL.  We are willing to fly anywhere in the world if needed, as we feel a bit on our own on this. The docs at MD anderson are helping, but its been a process and I am reaching out for another physician on the team to aid in in the cessation/desecalation aspect.  We are fully aware of the toxicity of the drug, and taking it in the manner of the previous 12 years is not an option, nor something that is wanted.  Thank anyone in advance for any advice or leads to physicians to see concerning this.  I feel the right physician would love to help as there is little data on patients stopping any TKI with ALL ph+, and my Dad is willing to go for it.  Thank you again.  This is an amazing resource, I wish there was one for ALL.

Hi Mike,

From a brief online search, it seems to me that your dad has had a very good (amazing) response to first-line treatment with dasatinib+HYPER CVAD.

MD Anderson is obviously doing some cutting-edge research in this hard to treat- and survive- disease. I include a link below which outlines current attitudes to how to treat this disease, intensive therapy or less intensive- see the link to full article below plus a short snip from the article regarding clinical trials and the future.

It seems that your dad is in a very good place... but, I am not at all sure that any clinician (including Prof. Clarke) would confidently support stopping dasatinib altogether. If your dad is now on 25mg it may be a good idea to wait until his next PCR result and if that proves to be at least stable or he has a reduction in BCR-ABL % back to where he was at 0.01- then he has some time to assess whether the cardiac issues and PE resolve.

I cannot find any research on TKI cessation in PH+ALL.... however, as he has been such a good responder then de-escalation to the lowest dose possible may well be the way to go. 

I hope this is helpful- I am certainly not an expert in PH+ALL - 

As far as finding online support groups like this for ALL- you could try the ACOR.org listserve and join the forum for Adult ALL 

Meanwhile, the following article is the most up to date I could find

Best wishes to you and your dad,

Sandy

Should Treatment of Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia Be Intensive?

Clinical Advances in Hematology & Oncology: Volume 14, Issue 11, November 2016

 

Ongoing and Future Trials

Ponatinib, the experimental third-generation pan-TKI that is active against the gatekeeper T315I mutation, currently is providing impressive results. Researchers at the MD Anderson Cancer Center recently published the results of a trial based on the combination of ponatinib and the hyper-CVAD regimen.6 Of the 37 patients enrolled (one of them was already in CR at the time of enrollment), all achieved a CR—with 26% achieving a CMR upon induction. The 2-year EFS and OS of 81% and 80.4%, respectively, are extremely encouraging. Nevertheless, 6 deaths related to toxicity were recorded among patients who had a CR.

In keeping with the GIMEMA strategy, we are currently completing a trial for elderly patients or those who are unfit to undergo intensive treatment (GIMEMA LAL 1811). This treatment is based on induction with ponatinib (45 mg) and corticosteroids for CNS prophylaxis, followed by ponatinib until progression or until a serious adverse event is recorded. Although preliminary data appear extremely promising, the study is still enrolling patients at press time.

One patient is being treated here at Sapienza University, an 85-year-old woman who was diagnosed with Ph+ ALL in February 2016 and achieved a CMR at day 22 of treatment. We temporarily interrupted ponatinib treatment because of an episode of hypertension and restarted the agent 2 weeks later at a reduced dose of 30 mg. At 6 months from diagnosis, her clinical status is excellent and she has a persistent CMR. This finding reinforces the notion that nonintensified treatment is at least as effective as intensified therapy, without producing dose-limiting toxicities.