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Should I switch TKI's?

Dx September 2016 and started on 600 MG Tasigna. Side effects were horrendous, but my PCR was MR 4.5 in 6 months, so I reduced dose to 20 Mg over the next 6 months and became undetectable during that time. Side effects improved markedly, but some still lingered.
In June of 2020, I attempted TFR but only lasted 75 days and restarted on 20 mg Sprycel and was undetectable again in 6 months. I started to have multiple musculoskeletal issues (mostly tendinosis and mild myalgia) and mild neuropathy in 2022 which has persisted to this day and has affected my ability to be as physically active as I was prior to 2022 (I am 72 years old). So with my oncologist's blessing and increased testing intervals, I reduced my dosage to 20 mg every other day and remained undetectable for 9 months. I decided to attempt TFR again but again only lasted 74 days before I had to restart on November 2025 when my PCR hit .04%. My last test in early January was .02%, so heading in the right direction.
Assuming I reach undetectable again, I am thinking about possibly switching from dasatinib to either 50 mg bosutinib or 20 mg asciminib. My oncologist is on board with this but suggested I try bosutinib first. So I asked AI which TKI would be best for me based on the side effects profile on dasatinib and my overall health profile, which is good. Here's what AI produced:

1. Asciminib - Best Overall Fit
- Excellent musculoskeletal, pulmonary, metabolic, and vascular profile.
2. Bosutinib - Strong Fit
- Low musculoskeletal and pulmonary impact; manageable GI effects.
3. Nilotinib - Mixed Fit
- Mild musculoskeletal effects; requires metabolic monitoring.
4. Dasatinib - Caution
- Moderate musculoskeletal effects; high pulmonary risk.
5. Imatinib - Least Aligned
- High musculoskeletal burden; likely to aggravate existing issues.

I'd appreciate any thoughts that anybody might have about this, including it's accuracy and any opinions on whether or not I should switch and if so, which TKI to switch to. Thanks

please excuse my 1-finger typing.
I am a bit older than your 72,still active, do my exercise and demanding chores to stay independent. and have a guiding oncologist that listens. diagnosed 3 yrs. ago.

I used imatinib 200 mg and sprycel/dasatinb 50 mg ,both for a year.
had good PCR results with both but failed both drugs due to rashes and extreme facial swelling., I believe reactions to the generic meds.

tried asciminib 40 mg for 3 months, no cardiac,circulatory,or GI issues. I have hand pain,which acupuncture helps.
lowered dose to 20mg 1 day,40 the next with bcr/abl 0.003% after next 3 months. plan to lower dose this spring to 20mg asciminib/day if next PCR test still 0.00something or better.
I believe my energy a bit lacking until after afternoon nap.I take the med at 1-2am on an empty stomach. I saw somewhere that the 1/2 life of med was 5-7 hrs. by 3pm abouts, I can do my hard exercise or demanding chores.

I believe I've seen studies where people having a PCR of 0.05% at 3 months TFR were still below 0.1% PCR years later. i've read so much,I am not sure. but I remember in my mind 0.05% at 3 months TFR was a good predictor of people staying TFR for 4 years+,still below 0.1%.
I can tell my energy and mental brightness in morning is better on the days I take 20 mg asciminib. I may try TFR after a few years on 20 mg asciminib.
no reason to reply. I will respond to a question. I sometimes have a hard time typing and expressing my thoughts coherently at same time.I am more interested in staying active/minimal side effects vs. TFR.

I appreciate your reply Bob. Sounds like asciminib has been the best so far for you based on the side effects profile. Continued good luck with this.

Hello!

So I was in a similar boat to you. I was on dasatinib, and tried TFR for reasons including musculoskeletal issues. I beat you 74 day stat, and lasted barely a month!

For my next TKI, nilotinib was ruled out as we don’t prescribe that any more in my hospital. So it was bosutinib, ponatinib, or asciminib. While we know how to treat with ponatinib a lot better than before, it wasn’t one I wanted. Bosutinub seems to have its niche, but asciminib felt more promising so that was my choice.

The GI problems for the first two weeks were significant, but this was expected. The musculoskeletal problems weren’t quite so expected, but they were pronounced. Getting out of bed was more of a rolling event than a standing one. Heat and massage really helped. It started to fade after about a month, and after two or maybe a little longer I was completely back to normal. Better, in fact as I now have less cramping than I had on dasatinib especially in my hands.

I was told it might not work super fast, and be patient. But I had the first undetectable result I have ever had soon after, and it’s been two years since then. My most recent test was positive at exactly MR5, so hardly a bad place to be!

Everyone’s circumstances are different, in terms of response and side effects but for me it turned out to be a great choice.

David.

Thanks David. What is your daily dose of asciminib? What was your PCR number just before the switch? Did you expect the initial bout of bad side effects? That is surprising to me.

Also, what was your daily dose of dasatinib right before the switch?

I was on 20mg of dasatinib before I stopped and tried TFR. 20mg seemed to be plenty for me to maintain MR4.5.

I take 80mg of asciminib now, once daily, which is the standard dose. We are thinking about reducing it, but I am not particularly minded to because I have no problems with that dose. However, as Jeff Lipton (Canadian CML expert doctor) said at a conference recently there is no drug that is totally safe so the only reason I would reduce now would be to avoid some potential future issue. So not really a very well evidenced reason!

We expected the GI side effects, but the MSK ones were not so expected but as I said they did run their course and I am much better on my current setup than I was on 20mg of dasatinib.

David.